Search for Fanconi Anaemia-related Research Papers and Clinical Trials here
1.RESEARCH PAPER SEARCH
Search the world’s papers to find relevant research using OpenAlex. You can include any of the words AND, OR, or NOT in your search (UPPERCASE) in the search term. Use quotation marks “ ” to search for an exact match of that phrase. Ignore differences in spelling for anaemia, leukaemia, tumour and oestrogen.
FANCONI ANEMIA TRIALS SEARCH
TRIALS SEARCH Option 1: Search for Fanconi Anaemia Trials on any of 3 databases: ClinicalTrials.gov (US), ClinicalTrials.eu or ClinicalTrialsRegister.eu and Search in new tab. The search includes the spelling variations anemia & anaemia and Fanconi and Fanconi’s.
TRIALS SEARCH Option 2: View the ClinicalTrials.gov trials directly in the section below and filter as required
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NCT03351868 :
FANCA Gene Transfer for Fanconi Anemia Using a High-safety, High-efficiency, Self-inactivating Lentiviral Vector
(UNKNOWN) Locations: Beijing, China, Beijing, China, Shenzhen, China Beijing, China, Beijing, China, Shenzhen, China Study Dates: Start: December 1, 2017 Study Overview: Fanconi anemia is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The major problem... Fanconi anemia is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The major problem for most patients is aplastic anemia, the blood counts for red blood cells, white blood cells, and platelets are low. In addition, some patients have physical defects usually involving the skeleton and kidneys. Fanconi anemia is typically diagnosed in childhood, and there is a high fatality rate. Hematopoietic stem cell transplantation (HSCT) is a common treatment for Fanconi anemia. However, there are many risks associated with HSCT including rejection of the transplanted cells and graft-versus-host disease. The primary objectives are to evaluate the safety of the self-inactivating lentiviral vector, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming immune abnormalities present at the time of treatment, assessment of gene correction efficiency, and finally the long-term correction of Fanconi anemia associated disease symptoms. More |
NCT04483544 :
Pembrolizumab and Olaparib in Cervical Cancer Patients
(Terminated) Locations: Miami, United States, Plantation, United States Miami, United States, Plantation, United States Study Dates: Start: December 3, 2020 Study Overview: No description available. No description available. |
NCT01286987 :
Study of Talazoparib, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors
(Completed) Locations: Scottsdale, United States, Scottsdale, United States, Los Angeles, United States, Los Angeles, United States, Los Angeles, United States, Los Angeles... Scottsdale, United States, Scottsdale, United States, Los Angeles, United States, Los Angeles, United States, Los Angeles, United States, Los Angeles, United States, Santa Monica, United States, Santa Monica, United States, Bloomington, United States, Indianapolis, United States, Indianapolis, United States, Indianapolis, United States, Ann Arbor, United States, Houston, United States, Sutton, United Kingdom More Study Dates: Start: January 3, 2011 | Actual Completion Date: January 30, 2017 Study Overview: No description available. No description available. |
NCT01917708 :
Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
(Completed) Locations: Atlanta, United States Atlanta, United States Study Dates: Start: January 1, 2014 | Actual Completion Date: September 19, 2019 Study Overview: Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only viable cure for children who suffer from a wide variety of rare, serious non-malignant diseases, such as Fanconi Anemia,... Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only viable cure for children who suffer from a wide variety of rare, serious non-malignant diseases, such as Fanconi Anemia, Hurler syndrome, and hemophagocytic lymphohistiocytosis. A major obstacle to the success of HSCT is morbidity and mortality from graft versus host disease (GVHD), driven by donor T cells recognizing and reacting against disparate host antigens. This trial is being conducted as a step toward testing the long-term hypothesis that the costimulation blockade agent abatacept can be added to a standard post-transplant GVHD prophylaxis regimen, cyclosporine and mycophenolate mofetil, to improve disease-free survival after unrelated hematopoietic stem cell transplantation (HSCT) using reduced intensity conditioning for children with non-malignant diseases (NMD). This study will have the following Specific Aims: Specific Aim #1: To conduct a multicenter pilot assessing the tolerability of abatacept (n=10). Patients will receive four doses (10 mg/kg IV on days -1, +5, +14 and +28), a schedule well tolerated by adolescents and adults with hematologic malignancies in a previous pilot. Abatacept will be combined with cyclosporine and mycophenolate mofetil. Specific Aim #2: To examine the immunological effects of abatacept in this setting. Three reduced intensity conditioning regimens that have been shown to be effective in achieving sustained engraftment in patients with non-malignant diseases are available for use, depending on the patient's disease: * Patients with Fanconi anemia will receive fludarabine, low dose cyclophosphamide, and anti-thymocyte globulin.
* Patients with severe aplastic anemia will receive low dose total body irradiation, fludarabine, cyclophosphamide, and anti-thymocyte globulin.
* Patients with other NMD will receive either the low dose total body irradiation regimen or an alemtuzumab, fludarabine, thiotepa, and melphalan regimen. More |
NCT00005891 :
Study of Allogeneic Bone Marrow Transplantation Following Cyclophosphamide and Radiotherapy in Patients With Fanconi's Anemia
(Completed) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: March 1, 2000 Study Overview: PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day -6 through -3 and total lymphoid radiotherapy on day -1. Patients undergo allogeneic bone marrow transplantation on day 0. PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day -6 through -3 and total lymphoid radiotherapy on day -1. Patients undergo allogeneic bone marrow transplantation on day 0. Patients are followed for at least 100 days. More |
NCT03398824 :
Pilot Study of Metformin for Patients With Fanconi Anemia
(Completed) Locations: Boston, United States Boston, United States Study Dates: Start: March 29, 2018 | Actual Completion Date: October 9, 2020 Study Overview: No description available. No description available. |
NCT00542373 :
Widefield Fluorescence and Reflectance Imaging Systems and Oral Tissue Samples in Monitoring Participants at Risk for Developing Oral Cancer
(Active, Not Recruiting) Locations: Houston, United States Houston, United States Study Dates: Start: August 27, 2007 | Estimated Completion Date: April 30, 2027 Study Overview: PRIMARY OBJECTIVES: PRIMARY OBJECTIVES: I. To compare images of oral mucosa, obtained at various wavelength combinations including 350 nm, 380 nm, 400 nm, and 450 nm excitation, to standard white light images, pathologic analysis of any biopsied tissue when available, and carcinogenic progression. OUTLINE: Participants' oral cavities are inspected by a clinician using a standard white light headlamp. Participants then undergo oral mucosa examination using wide-field reflectance and fluorescence imaging, and/or fluorescence spectroscopy imaging. Standard oral brush biopsies are also performed and examined microscopically. Participants may undergo repeated imaging procedures and biopsy during subsequent follow up visits. More |
NCT01071239 :
Hematopoietic Stem Cell Transplant for Fanconi Anemia
(Completed) Locations: Milwaukee, United States Milwaukee, United States Study Dates: Start: April 1, 2009 | Actual Completion Date: August 30, 2016 Study Overview: We are currently recruiting patients. We are currently recruiting patients. |
NCT00677079 :
Single Arm Study of BSI-201 in Patients With BRCA-1 or BRCA-2 Associated Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
(Completed) Locations: New York, United States New York, United States Study Dates: Start: June 1, 2008 | Actual Completion Date: December 1, 2008 Study Overview: Participants were treated for at least one 8-week cycle, with additional cycles as long as they had stable or responding disease (per RECIST criteria) and wished to remain on study. Participants were treated for at least one 8-week cycle, with additional cycles as long as they had stable or responding disease (per RECIST criteria) and wished to remain on study. Participants had a final follow-up visit within 4 weeks following the last dose of iniparib, after which time they were contacted by study staff every 3 months for the first year and every 6 months thereafter to assess disease status and survival. More |
NCT05973656 :
Role of Acetaldehyde in the Development of Oral Cancer
(Recruiting) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: July 8, 2022 | Estimated Completion Date: September 30, 2027 Study Overview: No description available. No description available. |
NCT00856388 :
Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders
(Completed) Locations: Buffalo, United States Buffalo, United States Study Dates: Start: January 14, 2009 | Actual Completion Date: March 13, 2019 Study Overview: PRIMARY OBJECTIVES: PRIMARY OBJECTIVES: I. To determine the transplant related mortality (TRM) of this reduced intensity transplantation (RIT) combination in a patient population that is usually not eligible for a full myeloablative allogeneic transplant. SECONDARY OBJECTIVES: I. To evaluate engraftment, safety, clinical response, evidence of graft-versus-malignancy effect/graft-versus-host disease (GVHD) and overall outcomes of treatment with our RIT regimen across a variety of hematological conditions. OUTLINE: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan\* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0. Note: \*Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan. After completion of study treatment, patients are followed up periodically. More |
NCT04656171 :
Microcephaly, Fanconi Anemia and Praxial Disorders
(Withdrawn) Locations: Paris, France Paris, France Study Dates: Start: January 30, 2023 Study Overview: Our hypothesis is that children with FA present a developmental dyspraxia. This condition is very penalizing for children especially regarding graphic tasks, handwriting, whether or not they have... Our hypothesis is that children with FA present a developmental dyspraxia. This condition is very penalizing for children especially regarding graphic tasks, handwriting, whether or not they have skeletal malformations of the upper limbs. Consequences are fatigue because of energy expended trying to execute fine motor movements correctly. Main objective: To identify gesture dyspraxia in order to propose a targeted rehabilitation leading to national recommendations. Main Evaluation Criteria : 1. measurement of fine motor praxia
2. quantification of dyspraxia Secondary Objectives : To identify the musculoskeletal or tendinous anomalies in the upper limbs of AF children and to assess their functional consequences. To determine if these upper limbs abnormalities could influence the somatosensory map of this part of the body in the cerebral cortex. Secondary Evaluation Criteria : 1. MRI of the hand and forearm, orthopedic examination and functional assessment
2. Previously obtained brain MRI data More |
NCT03579875 :
Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
(Recruiting) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: November 13, 2018 | Estimated Completion Date: January 5, 2029 Study Overview: No description available. No description available. |
NCT00272857 :
Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: August 1, 2004 | Actual Completion Date: October 1, 2007 Study Overview: FA is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The lack of white blood cells... FA is a rare, inherited disease that is caused by a gene defect and that primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The lack of white blood cells affects an individual's ability to fight infections, the lack of platelets may result in bleeding, and the lack of red blood cells usually leads to anemia. FA is typically diagnosed in childhood, and there is a high fatality rate. Bone marrow transplants are one common treatment for FA. However, there are many risks associated with transplantation, including rejection of the transplanted cells and graft-versus-host disease, a serious side effect in which donor cells attack the recipient's tissues. This study will use an experimental gene transfer procedure performed in a laboratory to insert a new FA gene into the participant's bone marrow cells. The gene-corrected bone marrow cells will then be re-infused into the participant and participants will be observed for successful gene transfer. The purpose of this study is to evaluate the safety and effectiveness of the FA gene transfer procedure and to determine the ability of the gene-corrected cells at generating new, healthy blood cells in individuals with FA. This study will enroll individuals with FA. Participants will be required to have the initial bone marrow transfer procedure performed at Cincinnati Children's Hospital, but will be allowed to see their own doctor for the majority of study visits. Participants will first attend a screening visit, which will include a physical exam, blood draw for laboratory testing, and a bone marrow biopsy. Bone marrow cells will be collected from eligible participants and sent to a laboratory for the FA gene transfer procedure. Several days later, the gene-corrected cells will be re-infused back into the participants via an intravenous catheter. Side effects will be closely monitored for 12 hours following the procedure and participants may be required to spend an overnight in the hospital. Following discharge from the hospital, participants will be required to stay in the Cincinnati area for 3 days to undergo daily evaluations and physical examinations. Participants will continue to be followed very closely for the first year after cell re-infusion. Study visits will be held weekly for the first 3 weeks, and then every 3 months for the remainder of the year. Visits will include physical examinations, blood collection, and liver function testing. Bone marrow testing will occur at Months 3, 6, and 12. Follow-up visits will occur yearly for up to 15 years and will include blood collection, a physical exam, and review of medical history. More |
NCT00000603 :
Cord Blood Stem Cell Transplantation Study (COBLT)
(Completed) Locations: Not specified Not specified Study Dates: Start: September 1, 1996 | Actual Completion Date: October 1, 2007 Study Overview: BACKGROUND: BACKGROUND: Bone marrow transplantation is an effective therapy for a variety of genetic and hematologic disorders. Donated bone marrow, which provides a source of stem and progenitor cells for bone marrow reconstitution, is obtained either from related donors, usually HLA-matched siblings, or from HLA-matched unrelated donors. Because of the limited availability of HLA-matched related donors, HLA-matched unrelated donors are frequently the only alternative source of bone marrow for transplantation. To provide matched volunteer bone marrow donors for unrelated recipients, the National Marrow Donor Program (NMDP) was established in 1986 to develop a national Registry of HLA-typed individuals who agree to donate bone marrow if needed. More than 3 million potential marrow donors are now enrolled. A limitation of the registry approach is the time needed to identify a donor and complete the necessary clinical evaluation and laboratory testing for histocompatibility, infectious diseases, and general good health. Moreover, a certain proportion of potential donors change their minds or otherwise become unavailable between the time they enter the Registry and the time they are called as a preliminary match for a patient. Another disadvantage is the marrow harvesting procedure which requires the normal donor to be hospitalized and given general anesthesia in an operating room. Finally, the NMDP Registry consists of potential donors that are primarily of European Caucasian ancestry. Although great strides have been made in increasing the numbers of African-Americans, Hispanics, Asian-Americans, and Native Americans, it is still more difficult to find matches for these ethnic minorities than for Caucasian patients. Human umbilical cord blood is an alternative source of hematopoietic stem and progenitor cells capable of reconstituting the bone marrow of recipients with a variety of diseases. Cord blood stem and progenitor cells from related donors have been successfully transplanted world-wide in children with genetic or hematologic diseases. These results suggested that cord blood from unrelated, HLA-matched donors also can be used for patients who need a transplant but don't have a related donor. The existing problems in unrelated-donor bone marrow transplantation with donor recruitment, bone marrow harvesting, and matching for antigens peculiar to a particular ethnic group would be reduced if typed, tested, and frozen umbilical cord blood could be made easily and rapidly available. Such a system, which could complement or partially replace the present process, has been shown to be feasible. In an NHLBI-sponsored program, investigators have collected and cryopreserved a bank of about 9,000 human UCBUs. In addition, successful searches and matches (including many 4/6 antigen matches) have resulted in more than 900 unrelated-donor, UCBU transplants to date. Preliminary data from both these unrelated-donor and other related-donor cord blood transplants suggest that there is less GvHD than if the source of the graft were adult bone marrow. The severity of GvHD also seems less even in highly mismatched recipients. One important question is whether or not 3/6 HLA matched transplants in children will have acceptable 180-day disease free survival. It also remains to be determined if the graft-vs-leukemia effect is also less or if unrelated-donor cord blood grafts are as durable as those from matched, related-donors. Most transplants conducted thus far have been in children. Hence another important question is whether or not there are sufficient numbers of stem cells in cord blood to support transplantation to an unrelated adult. The initiative was proposed by the Division of Blood Diseases and Resources staff and approved by the February 1995 National Heart, Lung, and Blood Advisory Council. The Requests for Proposals were released in June 1995. Contracts were awarded September 30, 1997. DESIGN NARRATIVE: The study is multicenter, with six Cord Blood Transplant Centers (CBTCs), two collecting and storage centers (Cord Blood Banks -- CBBs) and one Coordinating Center. Each CBB used the same protocol for recruiting donors, collecting, processing, testing, storage, retrieval from storage, reprocessing from the frozen state, and shipping. Each participating CBTC used the same patient selection criteria, preparative regimen for patients in the same class, initial graft-versus-host disease (GvHD) prophylaxis, indications for the use of cytokines, definitions for events and complications, and methods for evaluating immune reconstitution. The main study evaluated the impact of HLA 3/6 and 4/6 matching on outcome. The primary endpoint was 180-day disease free survival after UCBU transplantation. Secondary endpoints included engraftment, the frequency and severity of acute and chronic GvHD with stratification by degree of HLA match, overall survival, and immunologic reconstitution. Data were collected on banked UCBUs to define unit quality by nucleated cell count and flow cytometry of surface markers to identify effects on patient outcome. Recruitment ended December 31, 2003 with the accrual of 326 subjects. . More |
NCT02797977 :
A Phase 1/2 Trial SRA737 in Combination With Gemcitabine and Cisplatin or Gemcitabine Alone in Advanced Cancer Subjects
(Completed) Locations: Barcelona, Spain, Barcelona, Spain, Madrid, Spain, Madrid, Spain, Málaga, Spain, Valencia, Spain, Sutton, United Kingdom, Belfast, United Kingdom... Barcelona, Spain, Barcelona, Spain, Madrid, Spain, Madrid, Spain, Málaga, Spain, Valencia, Spain, Sutton, United Kingdom, Belfast, United Kingdom, Headington, United Kingdom, Cardiff, United Kingdom, Bebington, United Kingdom, Glasgow, United Kingdom, Leeds, United Kingdom, Leicester, United Kingdom, London, United Kingdom, London, United Kingdom, London, United Kingdom, Manchester, United Kingdom, Newcastle upon Tyne, United Kingdom, Sheffield, United Kingdom More Study Dates: Start: July 1, 2016 | Actual Completion Date: April 8, 2020 Study Overview: SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In... SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In cancer cells, intrinsic replication stress (RS) is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g., BRCA1 or FA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic RS. The critical role of Chk1 in mediating cellular responses to RS affords the opportunity to combine SRA737 with sub-therapeutic concentrations of the RS-inducing agent gemcitabine. Low concentrations of gemcitabine cause a prolonged cell cycle S-phase and induce hallmarks of RS without inducing overt cytotoxicity. Gemcitabine profoundly depletes DNA replication building blocks and targets proliferating cells by inducing RS through induction of stalled replication forks. In response, Chk1 has an important role in stabilizing and preserving replication fork complexes in the context of RS, preventing catastrophic replication fork collapse and double strand breaks. Extensive preclinical data, as well as clinical data, support the synergistic interaction between Chk1 inhibition and gemcitabine. The purpose of this clinical study is to: establish the safety profile, determine the MTD, and propose a RP2D and schedule for SRA737 in combination with low dose gemcitabine. In addition, the study aims to evaluate the preliminary efficacy of SRA737 in combination with low dose gemcitabine in prospectively-selected subjects with tumors that have predicted sensitivity to Chk1 inhibition. This clinical study consists of three phases: 1. A Standard-Dose Triplet Combo Dose Escalation Phase 1. This phase, which has concluded, evaluated a triplet combination of SRA737 with standard-dose gemcitabine and cisplatin in subjects with solid tumors.
2. A Low-Dose Gemcitabine Combo Dose Escalation Phase 1. Cohorts of 3 to 6 subjects are being given escalating doses of SRA737 on an intermittent schedule in addition to low dose gemcitabine until the combination MTD is reached. The dose or frequency of gemcitabine may also be reduced during this process and alternative dosing schedules for SRA737 may be considered. When the MTD or a minimum efficacious dose range has been achieved for SRA737, or when evidence of anti-tumor activity is observed, the gemcitabine dose may be escalated with corresponding decreases in the SRA737 dose as necessary for safety.
3. A Low-Dose Gemcitabine Combo Cohort Expansion Phase 2. After the MTD and/or RP2D has been identified, the trial will explore the preliminary efficacy of SRA737 plus low dose gemcitabine in prospectively-selected subjects with tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition via synthetic lethality. Enrollment for expansion cohorts may alternatively begin prior to the completion of dose escalation and determination of MTD or RP2D, if there is evidence of anti-tumor activity or if the minimal plasma concentration of SRA737 is maintained above a threshold at which sustained Chk1 inhibition is anticipated at 24 hours after dosing. This phase is targeting enrollment of genetically-selected patients into four expansion cohorts from specific indications that are predicted to have a high prevalence of such alterations, including locally advanced or metastatic: * high-grade serous ovarian cancer (HGSOC),
* small cell lung cancer (SCLC);
* soft tissue sarcoma (STS); and
* cervical/anogenital cancer. To qualify for enrolment into these cohorts, the subject's tumor must have evidence of predicted sensitivity to Chk1 inhibition based on factors including: * For subjects with HGSOC, documented somatic or germline BRCA1 and BRCA2 wild-type status will confer eligibility without requirement for prospective genetic profiling. If documented BRCA status is not available, genetic profiling may be performed prospectively to determine eligibility.
* Subjects with SCLC are eligible without requirement for prospective genetic profiling on the basis of very high prevalence of cancer related alterations in the tumor suppressor genes (eg, TP53 and RB1) in this population.
* For subjects with STS, and any others for whom genetic profiling is performed prospectively, eligibility will be determined by the sponsor's review of genetic abnormalities detected in genes in the following categories: * Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as RB1, TP53, etc.
* The DNA damage response pathway including ATM, BRCA1, BRCA2, mismatch repair genetic alterations and/or high microsatellite instability.
* Genetic indicators of replicative stress such as gain of function/amplification of Chk1 or ATR or other related gene.
* Oncogenic drivers such as MYC, CCNE1, etc.
* For subjects with anogenital cancer, known HPV positive status will confer eligibility without requirement for prospective genetic profiling. If HPV status is not known or not positive, genetic profiling (or HPV testing where appropriate) may be performed prospectively to determine eligibility. Subjects with cervical cancer or squamous cell carcinoma of the anus are eligible without requirement for prospective genetic profiling based on the very high prevalence of HPV positivity in these populations. Tumor genetics will be determine using Next-Generation Sequencing. More |
NCT00001399 :
Gene Therapy for the Treatment of Fanconi's Anemia Type C
(Completed) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: December 3, 1993 Study Overview: Fanconi anemia (FA) is a rare genetic disorder characterized by progressive pancytopenia, congenital abnormalities, and predisposition to malignancy. Therapy is currently limited to allogeneic marrow... Fanconi anemia (FA) is a rare genetic disorder characterized by progressive pancytopenia, congenital abnormalities, and predisposition to malignancy. Therapy is currently limited to allogeneic marrow transplantation; patients lacking a suitable donor usually die from aplasia or acute leukemia. Recently, mutation in a novel gene named FACC (Fanconi anemia C-complementing) has been identified as causing one type of FA. FACC mutations, which introduce splicing errors or stop codons, have been identified in 15% of FA patients. We have recently been successful in functional complementation of four FA cell lines using retroviral vectors to transfer a copy of the normal FACC gene. We also analyzed the ability of four viral vectors to functionally correct hematopoietic progenitor cells from a patient bearing a splice donor mutation. As for the lymphoid cell lines, these CD34 enriched cells were extremely sensitive to MMC. After injection of these progenitor cells with viral vectors bearing normal FACC, the progenitors gave rise to increased numbers of colonies both in the absence and presence of up to 5 nM MMC, whereas control cells were completely destroyed by 1 nM MMC. In summary, we have demonstrated that: (1) retroviral vectors can be engineered to transfer a normal FACC gene to FA(C) lymphoid cell lines and primary hematopoietic cells; (2) introduction of a normal FACC gene into CD34+ progenitors markedly enhances their growth in the absence and presence of MMC. This study is designed to determine whether hematopoietic progenitors transduced with the normal FACC gene can be re-infused safely into FA(C) patients. CD34+ cells obtained from G-CSF mobilized peripheral blood will be transduced ex vivo over a 72 hour period in the presence of IL-3, IL-6, and stem cell factor with the FACC retroviral vector. These transduced cells will be re-infused into FA(C) patients. Patients will be monitored for toxicities as well as evidence of successful gene transfer and expression. The procedure will be repeated up to a total of 4 times with each treatment 2-4 months apart. Theoretically, these rescued stem cells should have a selective growth advantage within the hypoplastic FA marrow environment in vivo. More |
NCT00896740 :
Gene Function in Bone Marrow Cells From Patients With Fanconi Anemia and From Healthy Participants
(Terminated) Locations: Portland, United States Portland, United States Study Dates: Start: March 1, 2002 Study Overview: OBJECTIVES: OBJECTIVES: * Describe the complete hematopoietic transcriptomes of Fanconi cells of every common complementation group (e.g., A, C, G, and F) as well as transcriptomes of neoplastic cells derived from bone marrow of patients with Fanconi anemia.
* Define large-scale dynamic gene expression data in these patients. OUTLINE: This is a multicenter study. Patients and healthy volunteers undergo bone marrow aspiration or biopsy for biological studies. Samples are analyzed for gene expression profiles using microarray assays. PROJECTED ACCRUAL: A total of 80 patients and 10 healthy volunteers will be accrued for this study. More |
NCT06519786 :
Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
(Recruiting) Locations: Alexandria, Egypt, Cairo, Egypt Alexandria, Egypt, Cairo, Egypt Study Dates: Start: October 5, 2022 | Estimated Completion Date: March 1, 2025 Study Overview: Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure, cancer susceptibility, and developmental abnormalities. Allogeneic hematopoietic stem cell transplantation offers... Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure, cancer susceptibility, and developmental abnormalities. Allogeneic hematopoietic stem cell transplantation offers curative therapy for hematologic complications of FA. Oxymetholone is commonly used in the management of FA as it improves blood counts, red cells, and platelets. However, its use is limited by its high toxicity profile. Metformin is a potential agent that reduces levels of both chromosomal radials and breaks in FA cells and increases the size of the hematopoietic stem cell compartment thus reducing cytopenia in patients with FA. More |
NCT02959398 :
Evaluation of Tomosynthesis for Characterization and the Management of Breast Lesions
(UNKNOWN) Locations: Paris, France, Paris, France Paris, France, Paris, France Study Dates: Start: November 20, 2017 Study Overview: No description available. No description available. |
NCT00004378 :
Stem Cell Transplantation (SCT) for Genetic Diseases
(Completed) Locations: Los Angeles, United States Los Angeles, United States Study Dates: Start: January 1, 1995 Study Overview: PROTOCOL OUTLINE: Patients receive either cyclophosphamide and high dose total body irradiation (TBI) or busulfan and cyclophosphamide. PROTOCOL OUTLINE: Patients receive either cyclophosphamide and high dose total body irradiation (TBI) or busulfan and cyclophosphamide. Cyclophosphamide IV is given on days -5 and -4 and TBI on days -2, -1, and 0. Busulfan is given orally every 6 hours on days -9 through -6 and cyclophosphamide IV on days -5 through -2. Patients rest on day -1. Patients receive bone marrow infusion on day 0. For GVHD prophylaxis, patients receive methotrexate on day 1, then on days 3, 6, and 11. Cyclosporine IV begins on day -2 over 12 hours, followed by continuous infusion for 21 days. Then, oral doses of cyclosporine are given every 12 hours to patients who tolerate oral feeding. Cyclosporine is continued 6 months posttransplant, then tapered 10% per week and stopped. Patients who receive genotypically HLA nonidentical stem cells undergo additional GVHD prophylaxis with methylprednisolone (IV or PO) or its equivalent every 12 hours on days 3 to day 100. Dose is then tapered as tolerated over 1 month. Patients who receive cord blood stem cells receive methylprednisolone instead of methotrexate for GHVD prophylaxis. Methylprednisolone is given 3 times daily beginning on day 5 and continuing until day 17. Then, methylprednisolone is tapered 10% per week as clinically tolerated. To accelerate engraftment, patients receive filgrastim IM daily beginning on day +1 and continuing until ANC equals 5000. More |
NCT04781790 :
French National Registry of Bone Marrow Failures
(Recruiting) Locations: Paris, France Paris, France Study Dates: Start: February 6, 2017 | Estimated Completion Date: February 6, 2027 Study Overview: No description available. No description available. |
NCT00167206 :
Stem Cell Transplantation for Fanconi Anemia
(Terminated) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: March 1, 2004 Study Overview: All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell... All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding. |
NCT00580021 :
Clinical Outcomes in Hereditary Cancer
(Withdrawn) Locations: New York, United States New York, United States Study Dates: Start: January 1, 2006 Study Overview: Compare the clinical characteristics and post-surgical outcomes (overall survival)of pancreatic cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 . Compare the clinical characteristics and post-surgical outcomes (overall survival)of pancreatic cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 . Compare the clinical characteristics and outcomes (time to progression) of breast cancer patients of Ashkenazi descent with or without germline founder mutations in BRCA1 or BRCA2 receiving paclitaxel chemotherapy for metastatic disease. More |
NCT03733249 :
Long Term Follow-up Study for Patients Enrolled on the BP-004 Clinical Study
(Terminated) Locations: Rome, Italy Rome, Italy Study Dates: Start: January 1, 2017 Study Overview: Subjects enrolled on the BP-004 study who have completed or discontinued from the study, and are beyond Day 180 will be requested to enroll on this long-term follow up protocol. Long term follow up... Subjects enrolled on the BP-004 study who have completed or discontinued from the study, and are beyond Day 180 will be requested to enroll on this long-term follow up protocol. Long term follow up for gene therapy clinical and safety endpoints will continue up to 15 years. |
NCT00005896 :
Phase I Pilot Study of CD34 Enriched, Fanconi's Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi's Anemia
(UNKNOWN) Locations: Not specified Not specified Study Dates: Start: March 1, 2000 Study Overview: PROTOCOL OUTLINE: Patients receive filgrastim (G-CSF) subcutaneously daily on days 0-6 followed by apheresis to collect peripheral blood stem cells (PBSC) on days 5-7. PBSCs are processed in vitro... PROTOCOL OUTLINE: Patients receive filgrastim (G-CSF) subcutaneously daily on days 0-6 followed by apheresis to collect peripheral blood stem cells (PBSC) on days 5-7. PBSCs are processed in vitro for enrichment of CD34 cells and transduced with a Fanconi's anemia complementation C (FACC) retroviral vector on days 5-10. Patients receive transduced PBSCs IV over no more than 2 hours on days 8-10. PBSC infusions may be repeated no more than every 2 months for up to 4 courses total. Patients are followed monthly for 3 months, every 3 months for 9 months, every 6 months for the next year, and then yearly thereafter. More |
NCT06065852 :
National Registry of Rare Kidney Diseases
(Recruiting) Locations: Bristol, United Kingdom Bristol, United Kingdom Study Dates: Start: November 6, 2009 | Estimated Completion Date: December 31, 2039 Study Overview: Background Background Rare diseases are arbitrarily defined as having an incidence such that they cannot be studied effectively on patient groups drawn from one or a few medical centres. A high proportion of such disorders have a genetic background and often these diseases are first expressed in childhood. The success of chronic and end-stage renal failure programmes in childhood permit increased numbers of these patients to survive into adulthood. There are 13 centres for paediatric nephrology in the UK. For a rare disorder that a paediatric nephrologist might diagnosis only once a year, and assuming 100% survival to adulthood, a renal physician might be asked to take over such a case only once in seven or eight years of practice. Research is hampered by this dilution of clinical experience. Similarly in adult practice there are rare complications of diseases or their treatment so that a nephrologist might encounter such an event less often than once in every 5 years. National aggregation of clinical experience is essential to further study. Research groups investigating a rare disease (Rare Disease Groups, RDGs) have difficulty accessing patients who are widely distributed. While rare disease groups are often successful in identifying novel genotypes in a few individuals, it is more difficult to define phenotype and undertake phenotype-genotype correlations. Moreover, the scarcity of patients makes it difficult to develop biomarkers or identify well-defined cohorts in which to test novel treatments. As a result, the progression and outcome for many rare diseases are unknown and treatment remains underdeveloped. Purpose The purpose of the National Registry of Rare Kidney Diseases (RaDaR; rare disease registry) is to facilitate translational and epidemiological research into rare kidney diseases by setting up and maintaining a comprehensive clinical database in partnership with Rare Disease Groups. RaDaR facilitates the identification of well-characterized cohorts of patients who may be invited to participate in clinical trials, the development of biomarkers, phenotype-genotype correlations or outcome studies. This will inform the development of clinical guidelines for specific rare diseases, audit treatment and outcome and further the development of future therapies. RaDaR provides an infrastructure to capture both generic and disease-specific clinical information and to collate longitudinal information. Patients and clinicians can view information about the conditions covered by RaDaR on RareRenal.org, which links closely with RaDaR. RaDaR is predominately aimed at UK patients; however international recruits who are consented in the UK by an NHS hospital are also eligible, subject to local approval. More |
NCT06045052 :
Eltrombopag for Treatment of Fanconi Anemia
(Completed) Locations: Madrid, Spain Madrid, Spain Study Dates: Start: December 2, 2020 | Actual Completion Date: August 29, 2023 Study Overview: Open-label, phase II study to assess the efficacy and safety of eltrombopag in the treatment of patients diagnosed with Fanconi anemia who have no immediate curative treatment for their bone marrow... Open-label, phase II study to assess the efficacy and safety of eltrombopag in the treatment of patients diagnosed with Fanconi anemia who have no immediate curative treatment for their bone marrow failure (n=10). The primary objective of this open-label, phase II proof of concept study is to assess the efficacy and safety of using eltrombopag for the treatment of patients with FA before conducting a larger phase II/III study. Specific objectives: * Primary: To assess the efficacy of eltrombopag on hematopoiesis by measuring changes in peripheral platelet, hemoglobin and neutrophil counts.
* Secondary: To assess the safety of eltrombopag in patients with Fanconi anemia. If the preliminary efficacy and safety results from the study are positive, we will propose its expansion to a multi-institutional Phase II/III study within the framework of the Spanish Fanconi Anemia Research Network. More |
NCT01319851 :
Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
(Terminated) Locations: Atlanta, United States Atlanta, United States Study Dates: Start: September 1, 2010 Study Overview: There are a large number of serious non-malignant diseases of childhood, most of them congenital and rare, which can be corrected by HSCT. These diseases are all characterized by deficiencies, either... There are a large number of serious non-malignant diseases of childhood, most of them congenital and rare, which can be corrected by HSCT. These diseases are all characterized by deficiencies, either in number or in function, of marrow derived cells. These diseases usually affect immune or blood cells and frequently involve transfusion therapy with erythrocytes, platelets or granulocytes. Examples of such diseases include sickle cell disease, thalassemia major, Glanzmann thrombasthenia, Wiskott-Aldrich syndrome, chronic-granulomatous disease, severe congenital neutropenia, leukocyte adhesion deficiency, Shwachman-Diamond syndrome, Diamond-Blackfan anemia, Fanconi anemia, dyskeratosis-congenita, Chediak-Higashi syndrome, and severe aplastic anemia. Allogeneic blood HSCT, whether performed for a malignant or a non-malignant condition, relies on the use of a pre-transplant conditioning regimen. Traditionally, very high doses of chemotherapy or total body irradiation have been utilized as conditioning. The use of intensive conditioning, which, practically speaking eliminates the host marrow and immune system, however, can produce serious and sometimes fatal infections and injuries to vital organs, such as the liver and lung. In children, the use of intensive conditioning can also produce serious late effects, including hypogonadism, stunted growth, impaired cognitive development and secondary malignancies. Over the past decade, there has been a move to minimize the risk for such complications by reducing the intensity of conditioning regimens. Added impetus for reducing conditioning intensity arose from the observation in transplantation for thalassemia and sickle cell disease that sustained mixed chimerism, that is partial donor engraftment, is usually sufficient to cure non-malignant diseases. This observation suggested that sustained engraftment could be achieved without "ablation" or elimination of the host marrow. Pre-clinical studies demonstrated in small and large animals that sustained mixed chimerism can be achieved with preparative regimens consisting of TBI doses as low as 100-300 cGy (by comparison, standard intensity regimens typically employ 1000 cGy or more in combination with chemotherapy). This approach was first translated in a clinical trial involving 45 adults with hematological malignancies who were not candidates for standard conditioning because of older age or serious co-morbidities. Using a single 200 cGy dose of TBI, sustained engraftment was achieved in 80% of cases and, remarkably, transplant related mortality was only 6.7% in this frail group of patients at 14 months. It is also notable that these transplants were performed primarily in the outpatient setting-the median length of hospitalization was 1 day. Low-dose TBI based conditioning has also been safely and effectively utilized for infants and children with severe combine immune deficiency and other severe immune deficiencies, undergoing related and unrelated donor transplantation. This clinical experience strongly suggests that if an effective low-dose TBI conditioning regimen can be developed for children with non-malignant diseases it could transform BMT from a costly, highly morbid, and sometimes life-taking procedure to a relatively inexpensive, safe and well-tolerated one. Thousands and thousands of children around the world suffer from sickle cell disease and thalassemia major. There is a myriad of other less common serious non-malignant hematological diseases, which have even more devastating effects, for which HSCT remains the only viable cure. Low-dose TBI based conditioning represents a minimally toxic approach to transplantation for these children-a way to overcome alloimmunization, however, is needed to make this approach more effective. Alefacept, the only currently FDA approved agent that specifically targets memory T cells, the investigators believe, holds the key to making low-dose TBI based conditioning more effective and could, thereby, dramatically alter the field of transplantation for non-malignant diseases. sustained donor engraftment needs to be developed. More |
NCT03600909 :
A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
(Terminated) Locations: New York, United States, Cincinnati, United States, Seattle, United States New York, United States, Cincinnati, United States, Seattle, United States Study Dates: Start: May 15, 2018 Study Overview: No description available. No description available. |
NCT07036731 :
A Study Comparing the Necessity of a Second Transurethral Resection in High-Risk Non-Muscle-Invasive Bladder Cancer Patients With Negative Results From Post-Initial Resection Urine Genome-Wide Low-Depth Sequencing
(Recruiting) Locations: Nanjing, China Nanjing, China Study Dates: Start: February 1, 2025 | Estimated Completion Date: August 31, 2029 Study Overview: No description available. No description available. |
NCT05910853 :
Whole Blood Biospecimen Collection for Subjects With Fanconi Anemia
(Terminated) Locations: Woburn, United States Woburn, United States Study Dates: Start: May 24, 2023 Study Overview: No description available. No description available. |
NCT00494234 :
Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer
(Completed) Locations: West Hollywood, United States, Boston, United States, Melbourne, Australia, Randwick, Australia, Duarte, Canada, Cologne, Germany, Kiel, Germany... West Hollywood, United States, Boston, United States, Melbourne, Australia, Randwick, Australia, Duarte, Canada, Cologne, Germany, Kiel, Germany, München, Germany, Tel Aviv, Israel, Hospitalet deLlobregat, Spain, Madrid, Spain, Lund, Sweden, Cambridge, United Kingdom, Edinburgh, United Kingdom, Fulham, United Kingdom, London, United Kingdom, Manchester, United Kingdom More Study Dates: Start: June 15, 2007 | Actual Completion Date: December 21, 2022 Study Overview: This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1-... This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd. |
NCT00258427 :
Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
(Completed) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: March 26, 2002 | Actual Completion Date: October 10, 2020 Study Overview: OBJECTIVES: OBJECTIVES: Primary * Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation. Secondary * Determine the tolerability of mycophenolate mofetil in these patients.
* Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
* Determine the incidence of major infections in patients with a history of major infections treated with this regimen.
* Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen
* Determine the probability of 1-year survival of patients treated with this regimen. OUTLINE: Patients are stratified according to donor/recipient HLA type (identical vs other). * Cytoreductive combination chemotherapy: Patients receive busulfan intravenously (IV) over 2 hours twice daily on days -7 and -6 and cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes once daily on days -5 to -2.
* Graft failure prophylaxis: Patients receive methylprednisolone IV twice daily on days -5 to 30 and anti-thymocyte globulin IV over 4-6 hours twice daily on days -5 to -1.
* Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours twice daily on days -3 to 100 (if patient has a matched sibling donor) or days -3 to 180 (if patient has another donor type). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 45.
* Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT (using bone marrow or umbilical cord blood) on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. After completion of study treatment, patients are followed periodically for 3 years. More |
NCT03476330 :
Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
(Active, Not Recruiting) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: May 8, 2018 | Estimated Completion Date: March 1, 2026 Study Overview: Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute... Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute myeloid leukemia (AML) and squamous cell carcinoma (SCC). Currently, the only curative treatment option for the hematological complications of FA include hematopoietic cell transplantation (HCT). The investigators hypothesize that quercetin will prevent or delay the development of SCC and associated complications, there by ameliorating or delaying the need for potentially lethal treatment with chemotherapy and/or radiation therapy for the same. This study is an open-label, single arm study. This study will enroll approximately 45 post-HCT patients with FA, and approximately 10 patients with FA without history of HCT. In both groups, patients with or without existing pre-malignant lesions or history of SCC will be allowed to participate, if they wish so and at the discretion of the PI. All patients will be treated with oral quercetin. The investigators will determine the efficacy of Quercetin in reducing buccal micronuclei (a surrogate marker of DNA damage and susceptibility to squamous cell carcinoma due to genomic instability) in post-HCT patients with fanconi anemia (FA). More |
NCT02797964 :
A Phase 1/2 Trial of SRA737 in Subjects With Advanced Cancer
(Completed) Locations: Sutton, United Kingdom, Belfast, United Kingdom, Headington, United Kingdom, Cardiff, United Kingdom, Bebington, United Kingdom, Edinburgh... Sutton, United Kingdom, Belfast, United Kingdom, Headington, United Kingdom, Cardiff, United Kingdom, Bebington, United Kingdom, Edinburgh, United Kingdom, Glasgow, United Kingdom, Leeds, United Kingdom, Leicester, United Kingdom, London, United Kingdom, London, United Kingdom, London, United Kingdom, Manchester, United Kingdom, Newcastle upon Tyne, United Kingdom, Sheffield, United Kingdom More Study Dates: Start: July 1, 2016 | Actual Completion Date: October 28, 2019 Study Overview: SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In... SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In cancer cells, intrinsic replication stress (RS) is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g. BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability, leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic RS. This study has been designed to: establish the safety profile; determine the pharmacokinetic profile; identify the optimal dose, schedule, and MTD; obtain preliminary evidence of activity; and evaluate SRA737's efficacy in prospectively-selected subjects with tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition via synthetic lethality. This clinical study consists of two phases, a Dose Escalation Phase 1 portion and a Cohort Expansion Phase 2 portion. In the Dose Escalation Phase 1 portion, cohorts consisting initially of a single subject will receive escalating doses of SRA737, administered orally on a continuous daily dosing schedule in 28-day cycles. Once an SRA737-related Grade 2 toxicity is observed in a dose escalation cohort during Cycle 1, that cohort will be expanded to 3 to 6 subjects, and subsequent dose level cohorts will follow a rolling 6 design until the MTD has been identified. In the Cohort Expansion Phase 2 portion, subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition will be prospectively enrolled into six indication-specific cohorts to explore the preliminary efficacy of SRA737. Subjects must have advanced or metastatic disease of one of the following types: * castration-resistant prostate cancer (mCRPC);
* high grade serous ovarian cancer (HGSOC) without CCNE1 gene amplification;
* HGSOC with CCNE1 gene amplification (or alternative genetic alteration with similar functional effect);
* non-small cell lung cancer (NSCLC);
* head and neck squamous cell carcinoma (HNSCC) or squamous cell carcinoma of the anus (SCCA); and
* colorectal cancer (mCRC). To qualify for enrolment in the Cohort Expansion Phase 2 portion, the subject's tumor must have a confirmed combination of mutations which are expected to confer sensitivity to Chk1 inhibition, determined by the Sponsor's review of genetic abnormalities detected in the following categories: * Oncogenic drivers such as CCNE1 or MYC, etc.
* Genes involved in the DNA repair process including BRCA1, BRCA2, FANC genes, mismatch repair (MMR) genetic alterations and/or high microsatellite instability.
* Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as TP53, RAD50, etc. For patients with HNSCC or SCCA, positive human papilloma virus (HPV) status is also considered for eligibility.
* Genetic indicators of replicative stress such as gain of function/amplification of CHEK1, ATR or other related genes. Tumor genetics will be prospectively determined using Next-Generation Sequencing. More |
NCT00753545 :
Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer
(Completed) Locations: Berkeley, United States, San Francisco, United States, West Hollywood, United States, Sunrise, United States, West Palm Beach, United States... Berkeley, United States, San Francisco, United States, West Hollywood, United States, Sunrise, United States, West Palm Beach, United States, Indianapolis, United States, Boston, United States, Boston, United States, Boston, United States, New York, United States, Providence, United States, Adelaide, Australia, East Bentleigh, Australia, Heidelberg, Australia, Melbourne, Australia, Nambour, Australia, Randwick, Australia, South Brisbane, Australia, Toorak Gardens, Australia, Innsbruck, Austria, Vienna, Austria, Wein, Austria, Brussels, Belgium, Leuven, Belgium, Vancouver, Canada, Toronto, Canada, Québec, Canada, Sherbrooke, Canada, Brno, Czechia, Brno, Czechia, Olomouc, Czechia, Prague, Czechia, Tallinn, Estonia, Tartu, Estonia, Bordeaux, France, Caen, France, Lyon, France, Nantes, France, Paris, France, Paris, France, Reims, France, Bonn, Germany, Düsseldorf, Germany, Essen, Germany, Freiburg im Breisgau, Germany, Göttingen, Germany, Hanover, Germany, Kiel, Germany, Marburg, Germany, München, Germany, Rostock, Germany, Ulm, Germany, Wiesbaden, Germany, Haifa, Israel, Holon, Israel, Jerusalem, Israel, Jerusalem, Israel, Nahariya, Israel, Ramat Gan, Israel, Tel Aviv, Israel, Ẕerifin, Israel, Amsterdam, Netherlands, Amsterdam, Netherlands, Bialystok, Poland, Grzepnica, Poland, Lublin, Poland, Poznan, Poland, Poznan, Poland, Poznan, Poland, Szczecin, Poland, Warsaw, Poland, Baia Mare, Romania, Cluj-Napoca, Romania, Iași, Romania, Suceava, Romania, Barnaul, Russia, Obninsk, Russia, Orenburg, Russia, Perm, Russia, Pyatigorsk, Russia, Saint Petersburg, Russia, Saint Petersburg, Russia, Voronezh, Russia, Yekaterinburg, Russia, Córdoba, Spain, Madrid, Spain, Madrid, Spain, Madrid, Spain, Valencia, Spain, Donetsk, Ukraine, Kharkiv Region, Ukraine, Kyiv, Ukraine, Kyiv, Ukraine, Lutsk, Ukraine, Odesa, Ukraine, Odesa, Ukraine, Ternopil, Ukraine, Uzhhorod, Ukraine, Dundee, United Kingdom, Edinburgh, United Kingdom, London, United Kingdom, London, United Kingdom, London, United Kingdom, Manchester, United Kingdom, Metropolitan Borough of Wirral, United Kingdom, Northwood, United Kingdom, Sutton, United Kingdom More Study Dates: Start: August 28, 2008 | Actual Completion Date: October 12, 2023 Study Overview: No description available. No description available. |
NCT00005898 :
Phase I/II Study of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Cell Transplantation in Patients With Fanconi's Anemia
(Completed) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: February 1, 2000 Study Overview: PROTOCOL OUTLINE: Donor bone marrow, peripheral blood, or umbilical cord blood is processed to harvest CD34+ cells. PROTOCOL OUTLINE: Donor bone marrow, peripheral blood, or umbilical cord blood is processed to harvest CD34+ cells. Patients receive preparative cytoreductive therapy comprising total body irradiation on day -6; cyclophosphamide IV over 2 hours on days -5 to -2; fludarabine IV over 30 minutes on days -5 to -2; methylprednisone IV on days -5 to 24; anti-thymocyte globulin IV over 4-6 hours on days -5 to -1; cyclosporine IV over 2 hours every 12 hours (every 8 hours for patients less than 40 kg in weight) on days -3 to 180, and then tapering in the absence of graft-versus-host disease; hematopoietic cell transplantation on day 0; and filgrastim (G-CSF) IV starting on day 1 and continuing until blood counts recover. Patients are followed at days 60, 90, and 180, and then annually for 3 years. More |
NCT01146210 :
Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia
(Completed) Locations: Monrovia, United States Monrovia, United States Study Dates: Start: May 1, 2009 | Actual Completion Date: May 1, 2016 Study Overview: PRIMARY OBJECTIVES: PRIMARY OBJECTIVES: I. Identify children with newly diagnosed acute myeloid leukemia (AML) treated on COG-2961 and COG-AAML03P1 who are at high risk of having de novo Fanconi anemia. II. Procure diagnostic samples from the COG AML Biology Repository and identify Fanconi anemia patients using western blot techniques. OUTLINE: Previously collected cryopreserved cells are analyzed via western blot to identify patients with Fanconi anemia. More |
NCT01772979 :
Study With Trabectedin in BRCA1 and BRCA2 Mutation Carrier and BRCAness Phenotype Ovarian Cancer
(UNKNOWN) Locations: Rome, Italy Rome, Italy Study Dates: Start: June 1, 2011 Study Overview: The main contribution to hereditary ovarian cancer comes from breast cancer (BRCA) genes mutations, which are responsible of 90% of hereditary ovarian cancer. The two susceptibility genes associated... The main contribution to hereditary ovarian cancer comes from breast cancer (BRCA) genes mutations, which are responsible of 90% of hereditary ovarian cancer. The two susceptibility genes associated with epithelial-type OC are BRCA1 and BRCA2. The BRCA proteins play an important role in the DNA repair mechanisms and are also involved in the control of the cell cycle checkpoints, in protein ubiquitinization and chromatin remodelling. Mutations in the BRCA genes have been extensively described in families affected by breast and/or OC; mutated BRCA1 has been found in up to 75% of families with hereditary OC - Recent data suggest that dysfunction of BRCA1andBRCA2, so-called BRCAness, maybe more prevalent than originally assumed. Both genetic and epigenetic mechanisms can create the BRCAness phenotype in at least a third of all epithelial ovarian cancers. The definition of BRCAness ovarian cancer is: high-grade serous cancers, high initial sensitivity to platinum drugs and retention of platinum-sensitivity through multiple relapses, longer history of disease, longer survival, longer TFIs between relapses. Yondelis® (trabectedin) is proposed to block the transcriptional activation of a subset of inducible genes without affecting their constitutive expression. Trabectedin binds to the minor groove of DNA, bending the helix to the major groove. This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins, and DNA repair pathways, resulting in perturbation of the cell cycle. Cell cycle studies of the action of trabectedin on tumor cells in vitro reveal that it decreases the rate of progression of the cells through S phase towards G2 and causes a prolonged blockade in G2/M at biologically relevant concentrations (20-80 nM). These cell cycle blocks are p53-independent and lead to a strong apoptopic response. Cells in G1 are more sensitive to the cytotoxic effects of trabectedin. These effects appear to be related to the unique 3-subunit structure, where two of the subunits or rings are involved in binding to the minor groove of DNA in guanine-cytosine rich sequences and alkylation N2 of guanine forming adducts that distorted the DNA helix structure and they are recognized by the TC-NER mechanism. DNA repair proficiency is a major determinant for the cytotoxicity of trabectedin: human cell lines deficient for genes essential for TC-NER activity as XPA, XPB, XPD, XPF, XPG, ERCC1, CSA and CSB are resistant to trabectedin, and this resistance is reverted by complementation of the cells with the corresponding gene. Trabectedin induces double strand breaks and that the BRCA1-/- human cell line HCC1937 and BRCA2Δ22/Δ22 mice cells are more sensitive to trabectedin and this hypersensitivity is reverted by complementation by the BRCA1 or BRCA2 gene. Based in these observations it was hypothesized that the NER machinery trapped in the DNA lesion induced by trabectedin was resolved by the cells producing double strand breaks that were repaired by the HRR machinery, and synergistic action of TC-NER and HRR machinery would be necessary for maximal trabectedin cytotoxicity. More |
NCT05485766 :
Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer
(Recruiting) Locations: Gifu, Japan, Okayama, Japan, Tokyo, Japan Gifu, Japan, Okayama, Japan, Tokyo, Japan Study Dates: Start: July 16, 2024 | Estimated Completion Date: September 30, 2028 Study Overview: No description available. No description available. |
NCT00344227 :
Prospective OCT Study With Lucentis for Neovascular AMD (PrONTO Study)
(Completed) Locations: Miami, United States Miami, United States Study Dates: Start: August 1, 2004 Study Overview: This is a Phase II, open-label study of intravitreally administered ranibizumab (LucentisTM). Ranibizumab is an anti Vascular Endothelial Growth Factor (VEGF) antibody fragment. Approximately 40... This is a Phase II, open-label study of intravitreally administered ranibizumab (LucentisTM). Ranibizumab is an anti Vascular Endothelial Growth Factor (VEGF) antibody fragment. Approximately 40 subjects with primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) will be enrolled. Lesion types included will be minimally classic or occult (predominatly occult) lesions or predominantly classic CNV, if the patient had received prior PDT (no more than 3 treatments). The study will be conducted at one study site. After reading the informed consent and having all their questions answered by the investigator and the coordinator, the subjects will sign the informed consent prior to participation in a screening period that could last up to 28 days to determine eligibility. Fluorescein angiograms (FA) will be used to determine CNV classification for study eligibility. In addition, optical coherence tomography (OCT) will provide information on retinal thickness, subretinal fluid and sub retinal pigment epithelium fluid for study eligibility. Fluorescein angiograms and OCT will be evaluated by the Bascom Palmer Reading Center. OCT images will be evaluated primarily using the standard Zeiss Stratus OCT software (Vers. 3) to determine study eligibility and retinal thickness. Proprietary software algorithms in development and not yet validated by the FDA may be used for future data analysis but will not be included in the intial data analysis. The angiographic features that will permit participation will include evidence of CNV with subfoveal involvement of the lesion. The OCT features that will permit participation will include retinal thickness (macular edema) ≥300 microns, subretinal fluid ≥100 microns in thickness, or a detachment of the retinal pigment epithelium ≥100 microns in thickness. ETDRS visual acuity measurements must be between 20/40 and 20/400. All eligible subjects will receive a ranibizumab dose of 500 micrograms at baseline and every 30 days thereafter for the first two months. ETDRS visual acuity testing and OCT measurements will be performed prior to injection. After each of the first 3 injections (baseline, Month-1, and Month-2), patients will return on post-injection days 1, 2, 4, 7, and 14. OCT measurements will be performed at those visits. ETDRS visual acuity measurements will be performed on each injection day and on post-injection day #14. At the Month-3 follow-up exam and thereafter, if the vision is stable or improved (stable visual acuity score= ±4 letters; improved visual acuity score ≥ 5 letters) from the previous visit, and there is no evidence of leakage from CNV as determined by fluorescein angiography and OCT, then no injection will performed. If the previous criteria are not met, then injections are continued monthly until these criteria are fulfilled. At that point, no further injections will be given until there is evidence of recurrent CNV. Enrolled subjects, who did not have predominantly classic CNV at baseline but converted to predominantly classic CNV within the study, will be offered veteporfin photodynamic therapy (PDT). If a patient receives PDT, there will be no injection of ranibizumab at that visit, and the next injection of ranibizumab will not be performed for at least 1 month. Patients will continue in the study and receive additional PDT at 3 months intervals if needed. There will alaways be at least a 1 month separation between PDT and the subsequent ranibizumab injection. The following criteria will need to be fulfilled to resume injections. There will need to be evidence of vision loss ≥ 5 letters associated with evidence of leakage from CNV as determined by OCT or fluorescein angiography, or a new-onset macular hemorrhage, or new onset classic CNV, or an increase in central macular thickness ≥ 100 microns. Only one eye will be chosen as the "study eye". Only the study eye will receive intravitreal injections of ranibizumab. Subjects will have scheduled monthly visits throughout the study for the evaluation of safety and efficacy. Subjects will have the first treatment of a ranibizumab injection by the injecting physician on Day 0 and will undergo retinal analysis by OCT on Days 1, 2, 4, 7 and 14 after the first 3 study treatments. At subsequent visits (every month \[30±7 days\]), the subject will have a safety evaluation by the evaluating physician prior to possible retreatment. After months 3 subjects will be contacted by the site personnel 2 days (±1 day) after each study treatment to elicit reports of any decrease in vision, eye pain, unusual redness, or any other new ocular symptoms; subjects will also be asked whether they have taken the prescribed self-administered post-injection antimicrobials. During the first 3 months, these questions will be asked when they return to clinic. Every 3 months, subjects will undergo fluorescein angiography and color fundus photography. Subjects will have a final safety visit at Month 24. Fundus photography and fluorescein angiography will be performed at baseline and at months 3, 6, 12, 18, and 24. Additional fluorescein angiography will be performed at visits when it is decided that injections should be stopped (if continued past Month-3) or be resumed due to decreased vision and possible evidence of leakage from CNV. Optical coherence tomography will be performed at baseline and on days 1, 2, 4, 7, 14 after each of the first 3 injections. Since preliminary data suggest that OCT imaging can detect the earliest manifestations of recurrent CNV, all patients will be monitored once injections have been stopped using monthly ophthalmologic exams, ETDRS visual acuity measurements, and OCT imaging at each monthly follow-up visit up to month 24. More |
NCT06287541 :
The Necessity of a Second Transurethral Resection in High-risk Non-muscle-invasive Bladder Cancer Patients With Negative Urine Biomarker After Initial Transurethral Resection
(Recruiting) Locations: Nanjing, China Nanjing, China Study Dates: Start: July 1, 2023 | Estimated Completion Date: July 1, 2027 Study Overview: This clinical trial aims to address the clinical question of whether a urine biomarker test can effectively guide the decision-making process regarding the necessity of reTURBT (repeat transurethral... This clinical trial aims to address the clinical question of whether a urine biomarker test can effectively guide the decision-making process regarding the necessity of reTURBT (repeat transurethral resection of bladder tumor) in patients with non-muscle-invasive bladder cancer (NMIBC). The primary objective is to assess whether patients with negative urine biomarker tests can safely avoid reTURBT. Participants eligible for enrollment in this study will be randomized in a 1:2 ratio into two groups:Group A: Participants assigned to this group will not undergo reTURBT. They will receive standard follow-up care as per institutional guidelines. Group B: Participants assigned to this group will undergo reTURBT. Following reTURBT, they will also receive standard follow-up care. The main task for participants will involve providing urine samples for the biomarker test before reTURBT. Those in Group B will additionally undergo reTURBT, a standard surgical procedure involving the removal of residual tumor tissue from the bladder.Throughout the study period, researchers will assess their recurrence-free survival rates and RFS. The goal is to determine whether the urine biomarker test can safely spare patients from unnecessary reTURBT while maintaining comparable RFS rates. This study adheres to ethical guidelines and has obtained approval from the appropriate institutional review boards. Participant confidentiality and data integrity will be strictly maintained throughout the study duration. The results of this trial have the potential to inform clinical practice guidelines and improve the management of NMIBC patients by offering a personalized approach to treatment decision-making. |
NCT02837523 :
Biomarker for Cystinosis Disease: BioCystinosis (BioCystinosis)
(Withdrawn) Locations: Rostock, Germany, Kochi, India, Mumbai, India, Colombo, Sri Lanka Rostock, Germany, Kochi, India, Mumbai, India, Colombo, Sri Lanka Study Dates: Start: August 20, 2018 Study Overview: Cystinosis is a rare, multisystem genetic disorder characterized by the accumulation of an amino acid called cystine in different tissues and organs of the body including the kidneys, eyes, muscles,... Cystinosis is a rare, multisystem genetic disorder characterized by the accumulation of an amino acid called cystine in different tissues and organs of the body including the kidneys, eyes, muscles, liver, pancreas and brain. Generally, Cystinosis is broken down into three different forms known as nephropathic Cystinosis, intermediate Cystinosis and non-nephropathic (or ocular) Cystinosis. Early detection and prompt treatment are critical in slowing the development and progression of symptoms associated with Cystinosis. The kidneys and eyes are the two organs most often affected. Individuals with nephropathic or intermediate Cystinosis ultimately require a kidney transplant. Non-nephropathic Cystinosis only affects the corneas of the eyes. Cystinosis is caused by mutations of the CTNS gene and is inherited as an autosomal recessive disease. The specific symptoms and severity of Cystinosis vary greatly from one person to another based upon several factors including age of onset and whether the disorder is promptly diagnosed and treated. The progression of the disorder can be slowed by early diagnosis and treatment. Eventually, Cystinosis can affect all tissues of the body. The age of onset for different symptoms varies greatly. • NEPHROPATHIC CYSTINOSIS (renal Fanconi disease) Nephropathic Cystinosis is the most frequent and most severe form of Cystinosis. The symptoms of nephropathic Cystinosis usually become apparent within the second half of the first year of life. Growth failure and renal Fanconi disease are usually the first noticeable complications of the disorder. Although infants appear normal at birth, by the age of one they often fall into the third percentile for height and weight. In addition, affected infants may have episodes of vomiting, poor appetite, and feeding difficulties that contribute (along with kidney dysfunction) to nutritional deficiency and the failure to gain weight and grow at the expected rate (failure to thrive). Ultimately, growth in untreated children with Cystinosis occurs at 60 percent the expected rate. Infants with nephropathic Cystinosis develop renal Fanconi disease, a rare disorder characterized by kidney dysfunction. The kidney tubules fail to reabsorb a variety of needed substances, including the compounds mentioned above as well as amino acids, phosphate, calcium, glucose, carnitine, certain proteins and electrolytes. Symptoms of renal Fanconi disease usually become apparent between 6 and 12 months of age and may include excessive thirst (polydipsia), excessive production and passage of urine (polyuria), electrolyte imbalances, vomiting, and dehydration. Children with nephropathic Cystinosis may also develop symptoms unrelated to the kidneys (extrarenal symptoms). Again, these findings are highly variable and affected children will not develop all of the symptoms discussed below. Specific extrarenal symptoms will vary greatly depending upon the age that treatment is begun and the specific organs that become involved; those organs can include the eyes, bone marrow, liver, pancreas, spleen, intestine, brain, thyroid, muscles and testes. Affected children may also develop deficiency of thyroid hormone production (hypothyroidism) due to cystine crystals accumulating in the thyroid. Symptoms of hypothyroidism are highly variable, but may include fatigue, feeling cold, dry skin, constipation and depression. Children with nephropathic Cystinosis do not produce tears, sweat or salivate normally. Tear production may be diminished causing the eyes to dry out. The increased longevity of individuals with nephropathic Cystinosis has revealed that additional complications affecting organs other than the kidneys can occur later during life. These complications develop due to the chronic accumulation of cystine crystals in individuals who have not been adequately treated by cysteamine, although they have undergone a kidney transplant. These additional complications generally develop between 20 and 40 years of age. Accumulation of cystine in muscle tissue can cause muscle dis- ease (myopathy) leading to progressive weakness and wasting of affected muscles. Impairment of muscles in the throat can lead to swallowing and feeding difficulties. Involvement of chest muscles can result in pulmonary insufficiency. A wide variety of gastrointestinal symptoms can develop including enlargement of the liver (hepatomegaly) causing high blood pressure of the main vein of the liver (portal hypertension), enlargement of the spleen (splenomegaly), gastroesophageal reflux, ulcers, inflammation of the esophagus (esophagitis), and dysfunction of the muscles of the gastrointestinal tract (dysmotility). Additional symptoms include inflammatory bowel disease, tearing of the bowel causing the contents of the intestines to flow into the abdominal cavity (bowel perforation), and inflammation of the peritoneum (peritonitis), which is the membrane that lines the abdominal wall and organs. Additional findings include metabolic bone disease and an inability to properly digest food due to a lack of digestive enzymes normally produced by the pancreas (pancreatic exocrine insufficiency). At any age, children may develop an abnormal sensitivity to light (photophobia) and irritation due to the formation of cystine crystals in the cornea. Adults with Cystinosis may also develop abnormalities affecting the eyes including spasms of the eyelids (blepharospasm), band keratopathy and pigmentary retinopathy. Band keratopathy refers to the accumulation of calcium deposits in a band across the central surface of the cornea, which can cause pain and decreased clarity of vision (visual acuity). Pigmentary retinopathy is characterized by progressive degeneration of the retina, the thin layer of nerve cells that line the inner surface of the back of the eyes. Pigmentary retinopathy can impair night and color vision and, eventually, can contribute to overall reduced clarity of vision. Individuals with nephropathic Cystinosis appear to have a higher rate of diabetes than the general population because of destruction of the pancreas by cystine accumulation. • INTERMEDIATE CYSTINOSIS Also known as nephropathic juvenile Cystinosis or adolescent Cystinosis, this form of Cystinosis is characterized by all of the signs and symptoms of nephropathic Cystinosis described above. However, onset of these symptoms does not occur until later perhaps around 8 years of age. Generally, the symptoms are less severe than in the classical infantile nephropathic form and have a slower progression. If untreated, end-stage renal failure in intermediate Cystinosis usually develops at some point between 15 and 25 years of age. There is a spectrum of disease severity in Cystinosis, with overlap of the in-fantile and intermediate forms. • NON-NEPHROPATHIC CYSTINOSIS Also known as ocular or "benign" Cystinosis, this form usually affects adult's during middle age; it was once called adult Cystinosis. Kidney disease does not occur in these individuals. The disorder appears to only affect the eyes. Untreated individuals with non- nephropathic Cystinosis eventually develop photophobia due to cystine crystal accumulation in the eyes. New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment. More |
NCT01019876 :
Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
(Completed) Locations: New York, United States New York, United States Study Dates: Start: September 1, 2002 | Actual Completion Date: September 7, 2021 Study Overview: This treatment program proposes the use of a reduced intensity chemotherapy regimen, which has been shown to be effective for inducing remission and cure in these diseases. Studies have shown that... This treatment program proposes the use of a reduced intensity chemotherapy regimen, which has been shown to be effective for inducing remission and cure in these diseases. Studies have shown that the use of non-myeloablative chemotherapy regimens have resulted in 75-100% engraftment (replacement of the recipient bone marrow with the donor bone marrow), and significantly reduced transplant related complications as compared to the standard myeloablative chemotherapy regimens. |
NCT00290628 :
Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
(Terminated) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: October 1, 1999 Study Overview: OBJECTIVES: OBJECTIVES: Primary * Determine the engraftment potential of umbilical cord blood (UCB) in patients with hematological cancers.
* Determine the safety of UCB transplantation in these patients. Secondary * Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment.
* Determine the incidence and severity of acute and chronic graft-versus-host disease.
* Determine the incidence of relapse in patients with malignant disease.
* Determine the probabilities of survival and event-free survival (EFS) at 1 and 2 years after UCB transplantation. OUTLINE: Patients are stratified according to degree of HLA disparity (0-1 vs 2-3 disparities between donor and recipient), donor type (related vs unrelated), and the basis of cell dose (\< 2 vs ≥ 2 x 10\^7 nucleated cells/kg recipient body weight). Patients are assigned to 1 of 4 treatment groups according to disease\*. NOTE: \*Patients with acute lymphocytic leukemia (ALL), secondary acute myeloid leukemia (AML), severe combined immunodeficiency, familial erythrophagocytic lymphohistiocytosis (FEL)/viral-associated hemophagocytic syndrome (VAHS), inborn errors of metabolism, aplastic anemia, Fanconi's anemia, or Diamond-Blackfan anemia who have an unrelated umbilical cord blood donor may proceed directly to transplantation. * Preparative regimen: * Group 1 (patients with chronic myelogenous leukemia, AML, myelodysplastic syndromes, or ALL): Patients receive cyclophosphamide IV once daily on days -7 and -6. Patients then undergo total-body irradiation (TBI) twice daily on days -4 to -1. Patients undergoing unrelated allogeneic umbilical cord blood transplantation (UCBT) also receive methylprednisone IV and anti-thymocyte globulin (ATG) IV twice daily on days -2 and -1.
* Group 2 (patients with infant leukemia): Patients receive busulfan orally or IV four times daily on days -9 to -6 and melphalan IV once daily on days -4 to -2. Patients undergoing unrelated allogeneic UCBT also receive methylprednisolone IV and ATG IV twice daily on days -2 and -1.
* Group 3 (patients with inborn errors of metabolism): Patients receive busulfan orally or IV four times daily on days -9 to -6 and cyclophosphamide IV once daily on days -5 to -2. Patients undergoing unrelated allogeneic UCBT also receive methylprednisolone IV and ATG IV twice daily on days -2 and -1.
* Group 4 (patients with aplastic anemia): Patients receive cyclophosphamide IV once daily on days -6 to -3 and ATG IV twice daily on days -5 and -3. Patients then undergo TBI once on day -2.
* Allogeneic UCBT: Patients undergo UCBT on day 0. Patients with inborn errors of metabolism receive methylprednisolone IV before and after UCBT on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of the following regimens: * Related donor UCBT: Patients receive cyclosporine IV over 2 hours or orally beginning on day -3 and continuing until day 60.
* Unrelated donor UCBT and myeloablative preparative regimen: Patients receive cyclosporine orally or IV over 2 hours twice daily beginning on day -3 and continuing until day 180. Patients also receive methylprednisolone IV twice daily on days 5-19.
* Unrelated donor UCBT and nonmyeloablative preparative regimen: Patients receive cyclosporine IV over 2 hours or orally twice daily beginning on day -3 and continuing until day 180. Patients also receive mycophenolate mofetil IV or orally beginning on day 5 and continuing until day 30 or 7 days after active GVHD is controlled. All patients receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover. Patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study. More |
NCT00453388 :
Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
(Completed) Locations: Oakland, United States, Nashville, United States, Seattle, United States, Milwaukee, United States, Curitiba, Brazil Oakland, United States, Nashville, United States, Seattle, United States, Milwaukee, United States, Curitiba, Brazil Study Dates: Start: February 1, 2007 | Actual Completion Date: June 1, 2013 Study Overview: PRIMARY OBJECTIVES: PRIMARY OBJECTIVES: I. Identify doses of total-body irradiation (TBI) that lead to sufficient probability of donor engraftment (\> 5% donor cluster of differentiation \[CD\]3 chimerism) by day +200. II. Evaluate the probability of severe acute graft-versus-host disease. SECONDARY OBJECTIVES: I. Evaluate the probabilities of overall survival, regimen-related toxicity (RRT), and recurrent hematopoietic malignancy in those patients with a prior underlying history of such. II. Examine the degree to which mixed chimerism provides for amelioration of symptoms (i.e., infections due to neutropenia, hemorrhage due to thrombocytopenia) associated with bone marrow failure. III. Determine if the FA complementation group and % initial mosaicism predict engraftment and RRT outcomes. OUTLINE: Patients are assigned to 1 of 4 treatment arms. NOTE: Patients no longer receive pre-transplant cyclophosphamide as of February 2009. After completion of study treatment, patients are followed up at 6 months and then annually thereafter. More |
NCT00899795 :
Evaluating Cell Damage in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, or Fanconi Anemia; in Patients Who Were Exposed to Alkylating Agents; and in Healthy Volunteers
(Completed) Locations: Portland, United States Portland, United States Study Dates: Start: June 1, 2002 | Actual Completion Date: October 1, 2010 Study Overview: OBJECTIVES: OBJECTIVES: Primary * Determine abnormal stromal function in patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or Fanconi anemia; in patients who were exposed to alkylating agents; and in healthy volunteers. Secondary * Determine whether clonal progenitors from patients with secondary AML or MDS are resistant to selected extracellular apoptotic cues.
* Determine whether stromal function in patients with secondary AML or MDS is more aberrant than stromal function in patients with primary AML or MDS.
* Determine whether cytotoxic agents known to induce secondary MDS or AML influence the supportive function of the bone marrow stroma.
* Determine whether cytoprotective agents reduce both cytotoxicity and genotoxicity in hematopoietic progenitor cells and stromal cells. OUTLINE: Patients and healthy volunteers undergo bone marrow sample collection. Progenitor cells are grown in culture. Cell survival is quantified by flow cytometric and cytogenetic analysis, sister chromatid exchange, and FISH for chromosome 11 changes (for etoposide-exposed samples only). PROJECTED ACCRUAL: A total of 24 patients and healthy volunteers will be accrued for this study. More |
NCT04522375 :
A Dose Escalation Study of FP-045 in Patients With Fanconi Anemia
(Withdrawn) Locations: Not specified Not specified Study Dates: Start: June 30, 2023 Study Overview: Dose escalation will begin with young adult/adolescent patients. The initial two patients enrolled in the study will be \> 15 years of age. These patients must complete the entire 28-day period of... Dose escalation will begin with young adult/adolescent patients. The initial two patients enrolled in the study will be \> 15 years of age. These patients must complete the entire 28-day period of treatment at Dose Level 1 prior to additional young adult/adolescent patients being enrolled. All 4 young adult/adolescent patients must complete 28 days of treatment at Dose Level 1, and cumulative safety must be reviewed by the Safety Review Committee (SRC), prior to the enrollment of pediatric patients. The initial two pediatric patients enrolled will be \> 6 years of age. These patients must complete the entire 28-day period of treatment at Dose Level 1 prior to additional pediatric patients being enrolled. A minimum of 8 and maximum of 12 pediatric patients will be enrolled to allow for at least 4 patients between the ages of 3-6. Study assessments will be conducted at each visit. Patients will be observed closely for Dose Limiting Toxicity (DLT) during each dosing period. Any patient experiencing a DLT will have study drug interrupted and will not be allowed to escalate to the next higher dose level. The patient may resume treatment at one dose level lower once the DLT has resolved to baseline or to ≤ Grade 1 in severity. The MTD will be defined as the dose level immediately below the dose level at which DLT occurred. Patients requiring an interruption in treatment of \> 3 weeks following a DLT will be withdrawn from the study. The MTD will be assessed separately for each individual patient. Following the completion of dose escalation, each patient will continue treatment at either the highest dose or their individual MTD, and then transition to the OBD for their age group (once defined), for a total of 3 months. Patients failing to receive 75% of planned doses for reasons other than adverse effects may be replaced. More |
NCT00084695 :
Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
(UNKNOWN) Locations: Hershey, United States Hershey, United States Study Dates: Start: September 1, 2003 Study Overview: OBJECTIVES: OBJECTIVES: Primary * Determine the impact of the use of umbilical cord blood as a source of hematopoietic stem cells for children with life-threatening oncologic, hematologic, or genetic/metabolic disorders in need of a stem cell transplant.
* Compare the incidence of graft-versus-host disease in patients receiving cord blood transplants in this study with historical data for unrelated donor stem cell transplants.
* Compare the incidence of engraftment in patients receiving cord blood transplants in this study with historical data for unrelated donor stem cell transplants. OUTLINE: * Preparative therapy: Patients are treated on 1 of 4 preparative therapy regimens. * Regimen A: Patients undergo total body irradiation (TBI) two times daily on days -7 to -4. Patients receive cyclophosphamide IV over 30-60 minutes on days -3 and -2 and anti-thymocyte globulin (ATG) IV over at least 6 hours on days -3 to -1.
* Regimen B (patients who do not receive TBI): Patients receive oral busulfan 4 times daily on days -8 to -5, and ATG IV over at least 6 hours and melphalan IV over 15-20 minutes on days -4 to -2.
* Regimen C (patients with Fanconi's anemia and related disorders): Patients undergo TBI on day -6. Patients receive ATG IV over at least 6 hours and methylprednisolone IV on days -5 to -1 and fludarabine IV over 30 minutes and cyclophosphamide IV over 30-60 minutes on days -5 to -2.
* Regimen D: Patients receive oral or IV busulfan 4 times daily on days -9 to -5, ATG IV over at least 6 hours on days -5 to -3, and cyclophosphamide IV over 30-60 minutes on days -5 to -2.
* Cord blood transplant: All patients undergo umbilical cord blood transplantation on day 0.
* Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine twice daily beginning on day -1. Patients also receive methylprednisolone IV twice daily beginning on day 5 and continuing until at least day 28. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study. More |
NCT00061763 :
Study of Deferasirox in Iron Overload From Beta-thalassemia Unable to be Treated With Deferoxamine or Chronic Anemias
(Completed) Locations: Oakland, United States, Stanford, United States, Arlington Heights, United States, Boston, United States, New York, United States, Philadelphia, United States Oakland, United States, Stanford, United States, Arlington Heights, United States, Boston, United States, New York, United States, Philadelphia, United States Study Dates: Start: May 1, 2003 Study Overview: No description available. No description available. |
NCT03924401 :
Acute GVHD Suppression Using Costimulation Blockade to Expand Non-malignant Transplant
(Active, Not Recruiting) Locations: Birmingham, United States, Wilmington, United States, Atlanta, United States, Chicago, United States, Boston, United States, Jackson, United States, Hackensack, United States, Buffalo, United States, New York, United States Birmingham, United States, Wilmington, United States, Atlanta, United States, Chicago, United States, Boston, United States, Jackson, United States, Hackensack, United States, Buffalo, United States, New York, United States Study Dates: Start: August 22, 2019 | Estimated Completion Date: January 1, 2026 Study Overview: Many serious non-malignant hematologic diseases (NMHD) affecting children, including severe aplastic anemia (SAA), Fanconi anemia (FA), sickle cell disease (SCD), and thalassemia can be cured by... Many serious non-malignant hematologic diseases (NMHD) affecting children, including severe aplastic anemia (SAA), Fanconi anemia (FA), sickle cell disease (SCD), and thalassemia can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). While the best results are achieved with HSCT from human leukocyte antigen (HLA)-matched siblings, most children lack such donors, and many children with NMHD are therefore transplanted with grafts from an adult unrelated donor (URD). Because URD grafts are less histocompatible, they are more likely to cause GVHD, a process driven by the reaction of donor T cells against incompatible host tissues. Despite the routine administration of immune suppression for GVHD prophylaxis, GVHD claims the lives of many and plagues others with incapacitating chronic illness. For NMHD, the threat of GVHD limits the use of URD HSCT to only the most severely affected children. In African-Americans and other ethnic minorities, the situation is compounded by the fact that most of these children lack fully matched URD and typically receive mismatched and matched grafts, which carry an increased risk for graft rejection. A more effective form of GVHD prophylaxis that does not compromise engraftment is urgently needed, both to improve outcomes for those children undergoing HSCT as well as to allow expansion of this curative therapy to the many children with NMHD who forego transplantation because of the risk for GVHD. The researchers have investigated the use of the co-stimulation blocking agent CTLA4-Ig (abatacept) to prevent GVHD. Study results to date indicate that abatacept strongly inhibits allo-reactive donor T cells and is clinically safe and effective. The clinical experience has included a variety of recipients: children and adults, peripheral blood stem cells (PBSC) and bone marrow (BM) grafts, as well as mismatched and matched unrelated and matched related donors; all have involved the administration of four IV doses of abatacept, on days -1, +5, +14, and +28, in combination with standard calcineurin inhibitor-based GVHD prophylaxis. Collectively, the results to date suggest that this combination, including abatacept, very effectively prevents acute GVHD. However, these results also suggest that protection against chronic GVHD is more limited. In this current trial, the researchers will attempt to more effectively prevent chronic GVHD by extending the administration of abatacept, giving eight doses (additional doses days +56, +84, +112, and +150). This trial will test the hypothesis that extended abatacept administration (combined with a standard regimen of tacrolimus and mycophenolate mofetil) will effectively prevent acute and chronic GVHD in children and adolescents receiving URD HSCT, without compromising their engraftment or reconstitution of protective immunity to infection. The ASCENT Trial is a single arm, multi-center, phase II study testing the hypothesis that extended abatacept administration (combined with a standard regimen of tacrolimus and mycophenolate mofetil) will effectively prevent acute and chronic GVHD in children and adolescents receiving URD HSCT, without compromising their engraftment or reconstitution of protective immunity to infection. The study will enroll 30 pediatric patients with serious NMHD undergoing URD HSCT. The trial will include two strata, based on donor matching. Stratum 1 will be for patients with 7/8 donors and stratum 2 will be for those with 8/8 (matched) donors. Study participants will be admitted to the hospital ten or eleven days prior to the day of transplant (day -10 or day -11) to complete a conditioning regimen to prevent the donor cells from being rejected. Patients will receive one of three reduced toxicity or intensity conditioning regimens based upon underlying disease and/or physician preference: (1) anti-thymocyte globulin, fludarabine, and a low dose of cyclophosphamide (FA patients only); (2) anti-thymocyte globulin, fludarabine, cyclophosphamide, and a low dose of total body radiation (SAA and other bone marrow failure disorders); or (3) alemtuzumab, fludarabine, melphalan, and thiotepa (hemoglobinopathy and non-SAA bone marrow failure disorders). All participants will receive 8 doses of abatacept (10 mg/kg intravenously on days -1, +5, +14, +28, +56, +84, +112, and +150). Recruitment is expected to last for about 2 years and participants will be followed for up to 3 years. Weight-based peripheral blood samples will be drawn longitudinally through two years to evaluate immune reconstitution. The primary objective is to determine the rejection-free, severe graft-versus-host disease (GVHD)-free survival in pediatric patients with serious non-malignant hematologic diseases (NMHD) undergoing unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) with abatacept added to conventional GVHD prophylaxis. The secondary objective is to characterize the impact of abatacept on infection and the reconstitution of protective immunity to infection. More |
NCT01113645 :
Impact of Cranioplasty On Cerebral Perfusion
(Completed) Locations: Paris, France Paris, France Study Dates: Start: July 1, 2010 | Actual Completion Date: April 1, 2012 Study Overview: Background: The decompressive craniectomy has recently experienced a renewed interest in the international neurosurgical community: the number of patients receiving decompressive craniectomy has... Background: The decompressive craniectomy has recently experienced a renewed interest in the international neurosurgical community: the number of patients receiving decompressive craniectomy has remarkably increased over last decades. Nowadays the most widely recognized indications for cranioplasty is aesthetic reconstruction and protection of brain against external injuries; it is usually performed several months after the craniectomy. Unexpected improvements of patients neurological status were noted but this phenomenon remains unexplained. This could be due to the reduction of local cerebral compression caused by atmospheric pressure, to improved cerebrospinal fluid hydrodynamics and possibly to the improvement of local and global cerebral hemodynamics, blood flow and metabolism. Main objective: To evaluate changes in local and global cerebral hemodynamics and blood flow before and after skull bone reconstruction. Patients and Methods: Pilot observational study on 20 patients. Inclusion criteria: Patient over 18 and up to 65 years who underwent decompressive craniectomy after severe head injury, subarachnoid hemorrhage, intracerebral hemorrhage, venous sinus thrombosis with hemorrhage / malignant edema and malignant middle cerebral artery stroke requiring of course reconstructive cranioplasty. Exclusion criteria: Patient not affiliated to the French NHS, pregnant and/or nursing women, patients being allergic to CT scan contrast products. Study Protocol: The patient who received a craniectomy is included in the study and an information notice given to him. All patients are evaluated by GOS (Glasgow Outcome Score) and neurocognitive tests by FAB (frontal assessment battery) and MMSE (mini mental state examination) scores 1 week prior and 6 and 24 weeks post cranioplasty. Furthermore, hemodynamic monitoring is performed by CT perfusion scan (with quantitative assessment of global and local cerebral flow) 1 week prior and 6 weeks post cranioplasty, as well as by trans-cranial Doppler 1 week prior and 6 and 24 weeks post cranioplasty. Expected Benefits: Better knowledge of local and global hemodynamic changes in patients after cranioplasty, its possible impact on neurological outcome and as a prognostic factor. Duration of the inclusion period: 1 year Duration of patient participation: 25 weeks (approximately 6 months) Total duration of the study: 1 year and 25 weeks (about 1 and ½ year) Number of patients: 20 Main endpoints: Evaluation of local and global cerebral hemodynamics and blood flow 6 weeks post cranioplasty by CT perfusion scan and trans-cranial Doppler. Secondary endpoints: - Evaluation of neurological and cognitive performances by GOS, FAB and MMSE scores 1 week prior and 6 and 24 weeks post cranioplasty. - Evaluation of local and global cerebral hemodynamics and blood flow by transcranial Doppler 24 weeks post cranioplasty. Statistical analysis: This is a pilot study whose size was determined on the basis of its feasibility (one year). Besides its own interest, this study will clarify the conditions for a future comparative study comparing different strategies of cranioplasty. |
NCT04784052 :
Depleted Donor Stem Cell Transplant in Children and Adults With Fanconi Anemia After Being Conditioned With a Regimen Containing Briquilimab
(Recruiting) Locations: Stanford, United States Stanford, United States Study Dates: Start: December 7, 2021 | Estimated Completion Date: December 1, 2027 Study Overview: No description available. No description available. |
NCT00171821 :
A Study Assessing the Efficacy and Safety of Deferasirox in Patients With Transfusion-dependent Iron Overload
(Completed) Locations: Adelaide, Australia, Camperdown, Australia, Clayton, Australia, Melbourne, Australia, Perth, Australia, South Brisbane, Australia, Westmead... Adelaide, Australia, Camperdown, Australia, Clayton, Australia, Melbourne, Australia, Perth, Australia, South Brisbane, Australia, Westmead, Australia, Graz, Austria, Linz, Austria, Vienna, Austria, Brussels, Belgium, Ghent, Belgium, Godinne, Belgium, La Louvière, Belgium, Leuven, Belgium, Guangzhou, China, Nanjing, China, Shanghai, China, Aarhus, Denmark, Copenhagen, Denmark, Herlev, Denmark, Hillerød, Denmark, Cairo, Egypt, Angers, France, Avignon, France, Bobigny, France, Créteil, France, Lille, France, Lyon, France, Nice, France, Paris, France, Pessac, France, Rennes, France, Toulouse, France, Vandœuvre-lès-Nancy, France, Augsburg, Germany, Braunschweig, Germany, Dresden, Germany, Düsseldorf, Germany, Frankfurt, Germany, Frankfurt am Main, Germany, Frieburg, Germany, Göttingen, Germany, Greifswald, Germany, Hanover, Germany, Mainz, Germany, München, Germany, Ulm, Germany, Athens, Greece, Larissa, Greece, Pátrai, Greece, Thessaloniki, Greece, Hong Kong, Hong Kong, Afula, Israel, Jerusalem, Israel, Petah Tikva, Israel, Bologna, Italy, Brindisi, Italy, Cagliari, Italy, Cona, Italy, Genova, Italy, Milan, Italy, Napoli, Italy, Orbassano, Italy, Palermo, Italy, Pavia, Italy, Pisa, Italy, Reggio Calabria, Italy, Roma, Italy, Sassari, Italy, Hazmiyeh, Lebanon, Kota Bharu, Malaysia, Kuala Lumpur, Malaysia, Nijmegen, Netherlands, Johannesburg, South Africa, Parktown, South Africa, Seoul, South Korea, Barakaldo, Spain, Barcelona, Spain, Madrid, Spain, Seville, Spain, Valencia, Spain, Geneva, Switzerland, Zurich, Switzerland, Taichung, Taiwan, Taipei, Taiwan, Bangkok, Thailand, Chaingmai, Thailand, Adana, Turkey (Türkiye), Ankara, Turkey (Türkiye), Istanbul, Turkey (Türkiye), Izmir, Turkey (Türkiye), Leeds, United Kingdom, Leicester, United Kingdom, London, United Kingdom, Manchester, United Kingdom, Sheffield, United Kingdom More Study Dates: Start: April 1, 2005 | Actual Completion Date: July 1, 2010 Study Overview: No description available. No description available. |
NCT00630253 :
Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
(Completed) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: February 17, 2000 | Actual Completion Date: October 10, 2020 Study Overview: OBJECTIVES: OBJECTIVES: Primary * To determine the probability of engraftment in patients with Fanconi anemia treated with cyclophosphamide, fludarabine phosphate, and antithymocyte globulin followed by HLA-genotypically identical sibling donor hematopoietic stem cell transplantation that is T-cell depleted. Secondary * To evaluate the incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
* To evaluate the incidence of regimen-related toxicity in these patients.
* To evaluate the 1-year survival of patients treated with this regimen.
* To evaluate the incidence of late secondary malignancies (e.g., squamous cell carcinoma of the head and neck or cervix) in patients treated with this regimen. OUTLINE: * Preparative cytoreductive therapy: Patients receive cyclophosphamide IV over 2 hours on days -6 to -3 and fludarabine phosphate IV over 30 minutes and anti-thymocyte globulin IV over 4-6 hours on days -6 to -2.
* T-cell depleted donor hematopoietic stem cell transplantation: Patients undergo T-cell depleted donor bone marrow or umbilical cord blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 1 and continuing until blood counts recover.
* Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper. Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count \[ANC\] \> 0.5 x 10\^9/L. After completion of study therapy, patients are followed periodically. More |
NCT00271089 :
Blood Cell Collection for Future Use in Individuals With Fanconi Anemia
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: August 1, 2004 | Actual Completion Date: October 1, 2007 Study Overview: FA is a rare, inherited disease that is caused by a gene defect to the CD34+ cells. It primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The lack of... FA is a rare, inherited disease that is caused by a gene defect to the CD34+ cells. It primarily affects an individual's bone marrow, resulting in decreased production of blood cells. The lack of white blood cells affects an individual's ability to fight infections, the lack of platelets may result in bleeding, and the lack of red blood cells usually leads to anemia. FA is typically diagnosed in childhood, and there is a high fatality rate. This study will use two methods to collect, purify, and store participant's CD34+ cells for future use in case of severe bone marrow failure. The collected cells will also be used by researchers to better understand the causes of FA and to possibly develop new treatments. This study will enroll individuals with FA. All participants will undergo a bone marrow biopsy within 3 months of study entry. Based on the results of this biopsy, participants will undergo either a bone marrow harvest procedure or a cytokine mobilized peripheral blood stem cell (PBSC) collection procedure. Prior to both procedures, medical history will be reviewed, blood will be drawn, liver and kidney function will be evaluated, and a physical examination will be performed. Participants who undergo the bone marrow harvest procedure will be admitted to the hospital, with a possible overnight stay for observation. The following day, participants will have a physical examination and blood draw for laboratory testing. A blood and/or platelet transfusion may be required following the procedure. Participants who undergo the PBSC procedure will be required to receive injections of G-CSF, a protein found normally in the body, twice a day for 4 to 8 days prior to the procedure; G-CSF has been found to help increase the amount of CD34+ cells in the blood. Once the CD34+ level is within a certain range, the PBSC procedure will begin through an IV placed in the arm or a temporary collection catheter placed under the participants' collarbone. Blood cells will be collected, with some cells separated out and the remainder of the cells infused back into the participant. The length of this procedure will vary for each participant; it will take 3 to 6 hours a day, for 1 to 4 days. Participants may require blood and/or platelet transfusions prior to and during the procedure. Following the bone marrow harvest and PBSC procedures, CD34+ cells will be isolated in a laboratory. The majority of the cells will be frozen and stored for future use by the participants. A small portion of the cells will be available for researchers to perform experimental research to better understand FA. The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record. More |
NCT06731036 :
Expanded Access to CD34+ Selection Utilizing Miltenyi CliniMACS Prodigy® for Patients Receiving Peripheral Blood Stem Cell Transplantations and Stem Cell Boosts
(AVAILABLE) Locations: Not specified Not specified Study Dates: Start: Not available Study Overview: No description available. No description available. |
NCT00004350 :
Evaluation of Fanconi Syndrome and Cystinosis
(Completed) Locations: Not specified Not specified Study Dates: Start: October 1, 1999 Study Overview: PROTOCOL OUTLINE: PROTOCOL OUTLINE: Patients receive a clinical and biochemical evaluation, including a psychometric assessment and molecular, renal, and thyroid studies. More |
NCT06227429 :
A Non-interventional, Post-Marketing Study to Describe Outcome of Nitisinone Treatment in HT-1 Patients
(Recruiting) Locations: Beijing, China, Chongqing, China, Hefei, China, Wuhan, China Beijing, China, Chongqing, China, Hefei, China, Wuhan, China Study Dates: Start: September 1, 2025 | Estimated Completion Date: June 30, 2027 Study Overview: This is a prospective, non-interventional, non-comparative, multicenter study to collect data on HT-1 patients in China treated with Nitisinone in a routine clinical setting. No tests or examinations... This is a prospective, non-interventional, non-comparative, multicenter study to collect data on HT-1 patients in China treated with Nitisinone in a routine clinical setting. No tests or examinations are mandated in the study, though the expectation is that most of the tests and examinations listed in the protocol will be performed in the context of routine clinical care and relevant data will be captured. At enrollment, data on patient treatment, medical and surgical history together with other patient characteristics will be captured.Patients enrolled in the study will be followed for at least 1 year and for a maximum of 3.5 years. The study aims to enroll at least 15 HT-1 patients aged 0-18 years. If adult patients are enrolled the study population will be larger as all eligible patients will be invited to participate. However, the enrollment will close when the target of 15 patients aged 0-18 years has been reached. More |
NCT00006127 :
Phase I Study of Amifostine in Patients With Bone Marrow Failure Related to Fanconi's Anemia
(UNKNOWN) Locations: Boston, United States Boston, United States Study Dates: Start: April 1, 2000 Study Overview: PROTOCOL OUTLINE: PROTOCOL OUTLINE: This is a dose escalation study. Patients receive amifostine IV over 3-5 minutes three times a week for three weeks. Cohorts of 3 patients receive one of three dose levels of amifostine. The maximum tolerated dose is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed weekly for 3 weeks. More |
NCT06213402 :
RADeep Multicenter European Epidemiological Platform for Patients Diagnosed With Rare Anemia Disorders (RADs)
(Recruiting) Locations: Barcelona, Spain Barcelona, Spain Study Dates: Start: November 30, 2021 | Estimated Completion Date: November 1, 2036 Study Overview: The Rare Anaemia Disorders European Epidemiological Platform (RADeep) is an initiative endorsed by the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet) under the frame of... The Rare Anaemia Disorders European Epidemiological Platform (RADeep) is an initiative endorsed by the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet) under the frame of the European Blood Disorders Platform (ENROL), the ERN-EuroBloodNet umbrella platform officially endorsed by the European Hematology Association (EHA) for European patients' registries on rare haematological diseases. RADeep will share pseudonymised level data with ENROL. RADeep supports the standardized collection of data of patients affected by any RADs at the European level, maximizing public benefit from data on RADs opened-up with the only restriction needed to guarantee patient rights and confidentiality, in agreement with the General Data Protection Regulation and applicable laws for cross-border sharing of personal data. RADeep has the following major objectives: 1. To collect and describe the demographics, disease-management, and treatment outcomes of patients diagnosed with RADs
2. To perform observational studies concerning research questions and to present outcomes in the fields of health related to organ damage and risk stratification for identification of trial cohorts for new drugs and/or development of research projects
3. To promote harmonization and best practices in the prevention, diagnosis, treatment and follow-up of RADs patients by the dissemination of reliable Guidelines and the translation of research results into clinical practice. More |
NCT03609814 :
Study of Clofarabine and Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation (HCT)
(Completed) Locations: San Francisco, United States San Francisco, United States Study Dates: Start: January 26, 2016 | Actual Completion Date: June 30, 2020 Study Overview: Fludarabine and clofarabine are nucleoside analogs with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation... Fludarabine and clofarabine are nucleoside analogs with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote stem cell engraftment. This is a single-center, prospective, non-interventional pharmacokinetic (PK) study investigating the clinical pharmacology of combination nucleoside analogue therapy in 24 children undergoing alloHCT at University of California, San Francisco Benioff Children's Hospital. Patients would receive clofarabine and fludarabine regardless of whether or not they decide to consent to PK sampling. Clofarabine and fludarabine doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing clofarabine and fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships. Subjects will undergo PK sampling of clofarabine and fludarabine drug concentrations over the duration of combination therapy (3 to 5 days). To evaluate sources of variability impacting clofarabine and fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling. To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant. More |
NCT02127905 :
Unrelated HSCT in Patients With Fanconi Anemia
(Withdrawn) Locations: Los Angeles, United States Los Angeles, United States Study Dates: Start: March 1, 2011 Study Overview: The major obstacle to successful alternate donor HCT for patients with Fanconi Anemia is graft failure. While T-cell depletion decreases the incidence of aGVHD, its effect on improving long term... The major obstacle to successful alternate donor HCT for patients with Fanconi Anemia is graft failure. While T-cell depletion decreases the incidence of aGVHD, its effect on improving long term survival is unproven. To potentially improve engraftment rate, we have chosen a relatively new immunosuppressive agent, fludarabine (FLU), FLU is an antineoplastic agent that has been shown to be an effective immunosuppressive agen in BMT conditioning therapy. The addition of FLU to the commonly used preparative regimen of CY and TBU in Fanconi Anemia patients may improve engraftment rates. Based on all presented data and its outcome, hematopoietic stem cell transplantation with the use of total body irradiation (450 cGy), cyclophosphamide (10 mg/kg IV) and fludarabine (35 mg/m2 IV) as preparative cytoreductive therapy has become the standard treatment for the hematologic manifestations of Fanconi Anemia at CHLA. However, the use of Isolex 300i will be replaced by CliniMACS in processing T-cell depletion. The CliniMACS CD34 Reagent System is an investigational medical device that has not yet been approved by the FDA. This device is used in vitro to select and enrich specific cell populations. When using the CliniMACS CD34 Reagent, the system selects CD34+ cells from heterogenous hematological cell populations for transplantation in cases where this is clinically indicated. Based on the gathered data, CliniMACS has not been a contributing factor in the toxicity of patients, although may have a potential of eliciting "antibody" reactions in some patients, the process has been of significant life-saving benefit as compared to the potential risks. More |
NCT02678533 :
Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and Plerixafor
(Completed) Locations: Paris, France Paris, France Study Dates: Start: February 10, 2017 | Actual Completion Date: May 3, 2019 Study Overview: Fanconi anemia is an autosomal recessive disease with an average survival of around 24 years old. The number of cells producted by bone marrow decreases around 5-10 years old. Hematological symptoms... Fanconi anemia is an autosomal recessive disease with an average survival of around 24 years old. The number of cells producted by bone marrow decreases around 5-10 years old. Hematological symptoms occur around 7 years old. 80% of patients with Fanconi anemia have clinical signs of bone marrow failure in the first decade of life. Generally macrocytosis is the first noticeable sign. Then it leads to thrombocytopenia, anemia and pancytopenia. Epidemiologic studies show that nearly all of the patients will have medullar aplasia before 40 years old, which is then the first cause of mortality. It must be emphasized that these complications may occur simultaneously for the same patient, so joint therapeutic intervention is needed. There is no basic treatment. Some currently used treatments cure cytopenias. These treatments involve blood transfusion, oral androgen, hematopoietic growth factor administration, such as Epo and G-CSF to treat anemia and neutropenia. These treatments are not curative. Hematopoietic stem cell transplantation is the only treatment able to restore permanently hematopoiesis. However, this treatment leads to a high level risk of developing solid tumors and other complications. All these data justify of developing a stem cells gene therapy treatment using a lentiviral vector expressing wild-type FANCA gene under CIBER promoter. Three studies have shown the potential number of cells to be mobilized in patients with Fanconi anemia. The aim is first, to show if administering G-CSF with plerixafor may lead to collect enough cells to potentially perform a gene therapy graft. Secondly the study will assess the tolerance, the stem cells' mobilization kinetic and collected cells' biological features. This study will be performed in Necker Children Hospital. 8 patients will be enrolled in order to reach 5 treated patients and to analyse how many injections and days are required to reach the cells' number goal. Sequential blood samples of patients will be drawn to monitor complete blood count (CBC), platelet, CD34+ cells rate and stem cells phenotype. The clinical and biological data will be anonymously entered in a electronic case report by the investigators up to the end of the study. More |
NCT00499070 :
Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
(Completed) Locations: Vienna, Austria, Ghent, Belgium, Prague, Czechia, Aarhus, Denmark, Freiburg im Breisgau, Germany, Dublin, Ireland, Pavia, Italy, Rotterdam, Netherlands, Barcelona, Spain, Zurich, Switzerland Vienna, Austria, Ghent, Belgium, Prague, Czechia, Aarhus, Denmark, Freiburg im Breisgau, Germany, Dublin, Ireland, Pavia, Italy, Rotterdam, Netherlands, Barcelona, Spain, Zurich, Switzerland Study Dates: Start: January 1, 2007 | Actual Completion Date: August 1, 2012 Study Overview: OBJECTIVES: OBJECTIVES: Primary * To evaluate the value of TCR V beta repertoire analysis for the determination of autoimmunity in refractory cytopenia (RC).
* To evaluate which immunophenotypic hematopoietic subclones are associated with oligoclonal T-cell expansion in RC.
* To evaluate the presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in RC. Secondary * To compare the molecular response with the hematologic response in patients with RC after treatment with immunosuppressive therapy (IST).
* To compare the molecular response with human leukocyte histocompatability antigen (HLA) expression in patients with RC after treatment with IST. OUTLINE: This is an open-label, multicenter, nonrandomized, prospective study. Patients undergo biopsy, bone marrow, and blood sample collection periodically for immunological studies. Samples are analyzed for TCR V beta repertoire and paroxysmal nocturnal hemoglobinuria (PNH) clone analysis via PCR heteroduplex analysis and immunophenotyping of CD14, CD16 , CD55, CD59, and CD24 expression via flow cytometry. More |
NCT00628251 :
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer
(Completed) Locations: Los Angeles, United States, San Francisco, United States, Boca Raton, United States, Boston, United States, New York, United States, Houston... Los Angeles, United States, San Francisco, United States, Boca Raton, United States, Boston, United States, New York, United States, Houston, United States, East Melbourne, Australia, Melbourne, Parkville, Australia, Randwick, Australia, Leuven, Belgium, Cologne, Germany, München, Germany, Haifa, Israel, Ramat Gan, Israel, Tel Aviv, Israel, Szczecin, Poland, Barcelona, Spain, Hospitalet deLlobregat, Spain, Lund, Sweden, Cambridge, United Kingdom, Edinburgh, United Kingdom, London, United Kingdom, Manchester, United Kingdom, Sutton, United Kingdom More Study Dates: Start: July 30, 2008 | Actual Completion Date: September 19, 2018 Study Overview: No description available. No description available. |
NCT00499187 :
Fanconi Syndrome Due to ARVs in HIV-Infected Persons
(Completed) Locations: Los Angeles, United States, Denver, United States, Miami, United States, Atlanta, United States, Indianapolis, United States, Baltimore... Los Angeles, United States, Denver, United States, Miami, United States, Atlanta, United States, Indianapolis, United States, Baltimore, United States, Detroit, United States, New York, United States, Cleveland, United States, Houston, United States, Vancouver, Canada, Toronto, Canada, Montreal, Canada More Study Dates: Start: September 1, 2007 | Actual Completion Date: March 1, 2011 Study Overview: No description available. No description available. |
NCT03609827 :
Study of Melphalan Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients
(Completed) Locations: San Francisco, United States San Francisco, United States Study Dates: Start: September 1, 2015 | Actual Completion Date: May 31, 2021 Study Overview: Melphalan is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote... Melphalan is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote stem cell engraftment. This is a single-center, prospective, non-interventional pharmacokinetics (PK) study investigating the clinical pharmacology of melphalan in 24 children undergoing allogeneic hematopoietic stem cell transplant (alloHCT) at University of California, San Francisco Benioff Children's Hospital. Patients would receive melphalan regardless of whether or not they decide to consent to PK sampling. Melphalan doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing melphalan exposure in pediatric alloHCT recipients. Population PK methodologies support the use of sparse sampling and therefore allow us to investigate drug levels in a pediatric population that would otherwise not be feasible using traditional intensive PK sampling. Subjects will undergo PK sampling of plasma melphalan drug concentrations over the duration of melphalan therapy (3 to 5 days). To evaluate sources of variability impacting melphalan exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling. To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant. More |
NCT00776958 :
Lynne Cohen Consortium Project: Multi-Center Database/Registry
(Completed) Locations: Birmingham, United States, Los Angeles, United States, New York, United States, Houston, United States Birmingham, United States, Los Angeles, United States, New York, United States, Houston, United States Study Dates: Start: July 1, 2008 Study Overview: Information Collection for Entry into Multicenter Registry: Information Collection for Entry into Multicenter Registry: If you agree to take part in this study, a study staff member will collect the following information by asking you at a clinic visit and checking your medical records. The following information will be entered in the registry: your demographic information (your sex, year of birth, and race/ethnicity) whether any member of your family has a history of ovarian and/or breast cancer whether any member of your family has any known genetic markers that may mean a higher risk of developing a cancer a brief summary of your history of breast and/or ovarian disease and whether you have any known genetic markers that may mean a higher risk of developing breast and/or ovarian cancer a brief summary of the results of the clinic visit on the day you agreed to take part in this study (Day 1) Follow-Up Information Collection: Each time you visit the M. D. Anderson high-risk clinic (either the high-risk breast cancer clinic or the high-risk ovarian cancer clinic), the study staff will check your medical records and enter in the registry any updates to your cancer risk information. You will also be asked if any family members have been diagnosed with ovarian and/or breast cancer, and this will be entered in the registry. If you miss any of your planned clinic visits, the study staff may contact you by phone to collect this information, contact you by mail to send you a questionnaire with this information, and/or reschedule your appointment. If you receive a questionnaire by mail, you will fill it out and mail it back to the research staff in the stamped, self-addressed envelope that will be provided to you. It should take about 5-10 minutes to complete. Study Data: The study staff plans to keep all personal identifying information (such as your name) strictly confidential. Your data will be handwritten on paper forms that will be stored in a locked file cabinet. The study staff will enter your data into the multicenter database (registry) with your participant identification (ID) number but not your name or other identifying information. The registry is password-protected. Only designated members of the study staff will have access to the participant ID numbers and be able to link the data to you. This is to allow medical information related to your data to be updated as needed. The linking information will be saved securely (on a password-protected computer) in the research office. The multicenter registry is called the Lynne Cohen registry. It is maintained at the University of Southern California Norris Comprehensive Cancer Center. Use of Registry for Planning Future Research: Lynne Cohen clinics make up the multicenter group of clinics that are involved in this study. If a researcher at any Lynne Cohen clinic is planning to perform a research study involving ovarian or breast cancer causes or prevention, he or she can contact the Lynne Cohen Foundation. A staff member at the Lynne Cohen Foundation will check to see how many patients are included in the registry. This will help the researcher find out how many people the researcher may be able to ask to join his or her study. That number of people will also help the researcher decide if the planned study is feasible. The number of patients in the registry is the only information that will be shared with these researchers. Length of Study Participation: Your participation in this study will last for as long as you agree to keep having this study information collected. When your participation in this study ends, the M. D. Anderson study staff will delete or destroy any personal identifying information and contact information collected. The rest of the study data will continue being stored in the registry. This is an investigational study. Up to 1000 patients will be enrolled in this multicenter study. Up to 200 will be enrolled at M. D. Anderson. More |
NCT02231710 :
Safety Study of Gene Modified Donor T Cell Infusion After Stem Cell Transplant for Non-Malignant Diseases
(Terminated) Locations: Seattle, United States Seattle, United States Study Dates: Start: February 1, 2015 Study Overview: This is a single arm dose finding study evaluating the safety and efficacy of a BPX 501 infusion (T cells genetically modified with the inducible Caspase 9 suicide gene) of 3x10E6 to 1X10E7 cells/kg... This is a single arm dose finding study evaluating the safety and efficacy of a BPX 501 infusion (T cells genetically modified with the inducible Caspase 9 suicide gene) of 3x10E6 to 1X10E7 cells/kg followed by a Rimiducid infusion on day 7 after a partially mismatched, related, T cell-depleted hematopoietic cell transplantation (HCT) in patients with non-malignant diseases. The purpose of this clinical trial is to determine the dose of BPX 501 T cell infusion with subsequent planned infusion of Rimiducid which can facilitate engraftment and prevent the occurrence of GVHD. |
NCT02931071 :
Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
(Completed) Locations: Barcelona, Spain, Madrid, Spain Barcelona, Spain, Madrid, Spain Study Dates: Start: September 1, 2013 | Actual Completion Date: October 1, 2018 Study Overview: No description available. No description available. |
NCT00001749 :
Medical Treatment for Diamond Blackfan Anemia
(Completed) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: July 1, 1998 Study Overview: Diamond Blackfan anemia (DBA) is a constitutional pure red cell aplasia of unknown etiology. There is laboratory evidence for an immune mechanism and most patients respond to corticosteroids. However... Diamond Blackfan anemia (DBA) is a constitutional pure red cell aplasia of unknown etiology. There is laboratory evidence for an immune mechanism and most patients respond to corticosteroids. However the relapse and failure rate are high, and corticosteroids are associated with many short and long term side effects. Patients who do not respond or who do not tolerate corticosteriods require lifelong red blood cell transfusion and iron chelation therapy. Allogeneic bone marrow transplantation is an option for those with a related histocompatible donor, but this procedure is associated with high mortality and morbidity. Other therapies have been tried without general success. Occasional responses to either ATG or cyclosporine have been reported, but no study has used both ATG and cyclosporine. In other blood/bone marrow disorders of immune etiology these drugs have synergistic effects. We propose a Phase II study to explore the combined use of ATG and cyclosporine as a rational approach to the treatment of Diamond Blackfan anemia. |
NCT00509509 :
High Risk Breast Cancer Screening Program
(UNKNOWN) Locations: Wan Chai, Hong Kong Wan Chai, Hong Kong Study Dates: Start: Not available Study Overview: No description available. No description available. |
NCT05598515 :
Time-restricted Feeding to Reduce Inflammation in Fanconi Anemia
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: November 11, 2022 | Actual Completion Date: December 7, 2023 Study Overview: No description available. No description available. |
NCT05236764 :
Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion
(Terminated) Locations: Houston, United States, Houston, United States Houston, United States, Houston, United States Study Dates: Start: December 6, 2023 Study Overview: This is a phase I/II study of haploidentical HCT (HHCT) with ex vivo TCRαβ+ and CD19+ depletion using the CliniMACS device in patients with hematological malignancies and non-malignant disorders.... This is a phase I/II study of haploidentical HCT (HHCT) with ex vivo TCRαβ+ and CD19+ depletion using the CliniMACS device in patients with hematological malignancies and non-malignant disorders. HHCT will be performed according to current standards of care at the Center for Cell and Gene Therapy (CAGT) within Texas Children's Hospital (TCH) and Houston Methodist Hospital (HMH), including the use of a standard chemotherapy conditioning regimens, supportive care and standard follow-up laboratory assessments. The study will determine efficacy of this strategy in terms of engraftment, and safety in terms of rates of acute and chronic graft versus Host Disease (GvHD), one-year overall survival (OS) and transplant-related mortality (TRM). The peripheral blood hematopoietic cell product will undergo negative selection of TCR αβ following the standardized protocol in the user's manual for the CliniMACS (Miltenyi Biotech, Germany). TCR αβ+ T-cells are labeled by CliniMACS TCR αβ-Biotin (murine anti-TCR αβ monoclonal antibodies conjugated to biotin) which allows the TCR αβ+ T-cells to be magnetically labeled with CliniMACS Anti-Biotin Microbeads (murine anti-biotin monoclonal antibodies conjugated to superparamagnetic iron dextran particles) for depletion. The CD19+ B cells are labeled by CliniMACS CD19 microbeads which allows the CD19+ B cells to be magnetically labeled for depletion. All unlabeled cells are selected as target cells which should contain a minimum amount of TCR αβ+ and CD19+ cells. The microbeads used for labeling are approximately 50 nanometers in diameter and do not require removal prior to patient infusion. In January 2014, the U.S. Food and Drug Administration (FDA) has approved the Miltenyi Biotec's CliniMACS CD34 Reagent System as a Humanitarian Use Device for the prevention of GvHD in patients with acute myeloid leukemia (AML) in first complete remission undergoing allo-HCT from HLA-matched related donor. More |
NCT00858078 :
A Qualitative Exploration of the Impact of Positive BRCA1/2 Mutation Status on the Lives of Young Women
(Completed) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: June 21, 2011 | Actual Completion Date: April 3, 2015 Study Overview: Background: Background: * BRCA1/2 mutations are present in approximately 1 in 800 individuals in the US, with higher frequency among some populations (e.g., Ashkenazi Jews)
* Mutations confer a lifetime breast cancer risk approaching 90%, ovarian cancer risk as high as 60%, and lesser increases in absolute risks of selected other cancers (e.g., male breast, prostate, pancreas).
* We have successfully conducted follow-up interviews with women in our original studies who had known about their mutations for less than six months, and have gleaned useful longitudinal data. We now propose to conduct additional follow-up interviews with participants who were in the process of making significant decisions about risk-management, relationships, family formation, and other pertinent issues at the time of their initial interviews.
* Additionally, previous research indicates that women who undergo genetic testing very early in young adulthood (i.e., prior to their 25th birthdays) have genetic counseling and support needs that are different from the broader BRCA-positive population.
* Research regarding how these very young mutation carriers manage and accommodate their risk is scarce. We propose to conduct two focus groups with women who considered and/or underwent genetic testing for BRCA prior to their 25th birthdays, who are attending the Joining FORCES annual conference in Orlando, FL June 23-25, 2011.
* The Study Application has been updated with this amendment to reflect the following changes: 1) the inclusion of males who may be enrolled only in the Family Group Interview component of the study \& 2) the inclusion older individuals as some women may wish to include male or older members of their family in Family Group Interview portion of the study. To reflect this change the maximum age for study participants has been increased to 100 years of age and males are no longer listed as excluded from the study. Objectives: * For follow-up to previous study: \-- Conduct follow-up telephone interviews with participants who were newly-tested at the time of original data collection to increase understanding of their mutation-positive experience longitudinally.
* For 25 \& Under study: * Conduct two (2) focus group sessions at the Joining FORCES Annual Conference, focusing on the unique genetic counseling and support needs of women who consider or undergo genetic testing for BRCA1/2 prior to age 25. Eligibility: * For follow-up to previous study: \-- Individuals who were in the process of making decisions relative to their status as mutation positive at the time of their previous interviews will be re-interviewed, in order to learn about their longitudinal experiences and expand the data set.
* For 25 \& Under study: * Women aged 18-24 who have received a positive BRCA1/2 mutation test result.
* Women aged 25-30 who considered or completed genetic testing for BRCA1/2 prior to their 25th birthdays
* English-speaking
* Attending the 2011 Joining FORCES Annual Conference. Design: * For follow-up to previous study: * Individuals will be invited to participate in a second telephone interview, during which they will be asked to describe their mutation-related experience since their previous interviews (approximately two years ago).
* Questions for each participant will be specifically tailored based on their previous interview data. Telephone interviews are anticipated to be approximately 60 minutes in length.
* \*\*Note: In cases where an individual eligible for follow-up is also participating in the multi-generational family interview (see Amendment A), the individual interview conducted as part of that study will take the place of a follow-up telephone interview.
* For 25 \& Under Study * Individuals who meet eligibility criteria will be invited to participate in either of two focus group sessions being held during the FORCE conference.
* Following the conference, each participant will be contacted via telephone to complete a brief family history interview, in order to provide context for the data collected during the focus group.
* Focus groups will be conducted using a prepared guide (see attachment).
* Participants will be entered into a raffle at each session, and one participant in each session will win a $50 gift card.
* Focus group sessions and telephone family history interviews will be audio recorded; then, they will be transcribed and analyzed using modified grounded theoretical design and QSR NVivo v8 software. More |
NCT02720679 :
Investigation of the Genetics of Hematologic Diseases
(Recruiting) Locations: Memphis, United States Memphis, United States Study Dates: Start: June 17, 2016 | Estimated Completion Date: July 1, 2050 Study Overview: Participants will be individuals (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder. We propose to use genomics, transcriptomics, proteomics and... Participants will be individuals (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder. We propose to use genomics, transcriptomics, proteomics and metabolomic analysis coupled with family linkage studies to identify causal mutations in individuals with undefined hematologic disorders and to characterize genetic modifiers of defined monogenic blood diseases. A detailed medical history will be obtained, including demographic information for each proband. For each identified biologically related family member, a medical history questionnaire will be obtained. The family history and pedigree will be reviewed in conjunction with a geneticist/genetic counselor. The implications of genetic testing will be explained. If participants consent for future contact, this will take place annually for updates on medical and family history. All probands will provide peripheral blood samples, and probands who are undergoing a bone marrow aspirate/biopsy for clinical purposes will provide additional aspirates. Biological family members will provide peripheral blood samples as a source for DNA. More |
NCT02039388 :
Lavage of the Uterine Cavity for the Diagnosis of Serous Tubal Intraepithelial Carcinoma
(Completed) Locations: Graz, Austria, Linz, Austria, Vienna, Austria, Leuven, Belgium, Prague, Czechia, Brno, Czechia, Pilsen, Czechia, Copenhagen, Denmark, Berlin, Germany, Essen, Germany, München, Germany, Dublin, Ireland, Nijmegen, Netherlands, London, United Kingdom Graz, Austria, Linz, Austria, Vienna, Austria, Leuven, Belgium, Prague, Czechia, Brno, Czechia, Pilsen, Czechia, Copenhagen, Denmark, Berlin, Germany, Essen, Germany, München, Germany, Dublin, Ireland, Nijmegen, Netherlands, London, United Kingdom Study Dates: Start: November 1, 2013 | Actual Completion Date: December 31, 2021 Study Overview: The term "high grade serous carcinoma" (HGSC) describes a group of ovarian, tubal and peritoneal cancers with an aggressive biological behavior. HGSC is the leading cause of death from gynecologic... The term "high grade serous carcinoma" (HGSC) describes a group of ovarian, tubal and peritoneal cancers with an aggressive biological behavior. HGSC is the leading cause of death from gynecologic malignancy in western civilized countries. Women affected, usually have advanced stage disease with metastatic spread throughout the abdominal cavity at time of diagnosis. Five-year survival rates are in the range of 10 to 30 percent. The specificity of current diagnostic tools (CA-125 and transvaginal ultrasonography) is low and ineffective at detecting HGSC early enough to improve clinical outcomes. Definitive diagnosis of HGSC mostly relies on surgical confirmation. These findings underline the need for an effective test for early detection of HGSC. In the general population, the lifetime risk is 1.5 percent. Women with germ line mutations in the BRCA1 and BRCA2 gene or a strong family history of epithelial ovarian cancer carry a high risk for breast cancer and/or HGSC development. Familial or inherited syndromes account for approximately 13 percent of cases of invasive epithelial ovarian and fallopian tube cancer. The lifetime risk of ovarian cancer is 35 to 46 percent in women with BRCA1 gene mutations and 13 to 23 percent in those with BRCA2 mutations. Again, even in this population with high-risk for HGSC, the specificity of CA-125 and transvaginal ultrasonography is still too low and ineffective to improve clinical outcomes. Over the last years, increasing scientific evidence conglomerated that a large proportion of not only familial HGSC develop primarily in the lining of the fallopian tube, that resembles Müllerian epithelium. These precursor lesions are called "serous tubal intraepithelial carcinomas" (STICs) and are characterized by p53 overexpression on immunohistochemistry and high Ki-67 labelling index indicating a high proliferation index. In over 90 percent, STICs carry mutations in the TP53 tumor suppressor gene. As for today, risk reducing bilateral salpingo-oophorectomy (rrBSO) is the most effective approach to reducing the risk of HGSC in high risk women. Among women with an increased risk of HGSC (most with BRCA mutations) who underwent rrBSO, 4 to 17 percent are found to have a STIC or even invasive neoplasm, and approximately 80 percent of these neoplasms are in the ampullar part of the fallopian tube. Recent findings highlighted the malignant potential of STICs. On histopathological specimen, intraluminal shedding of tumor cells from STICs can be frequently demonstrated in the fallopian tube. This shedding of tumor cells from STICs appears to be a risk factor for early transperitoneal metastasis frequently found in HGSC. There is a strong clinical need for screening for STICs, since they are the precursor lesion of HGSC. These facts underline the importance of an effective - non-invasive - test for early detection of STICs. The ovarian surface, the fallopian tubes, the uterine cavity and the peritoneal cavity all together form a communicating compartment. The physiological function of the ciliated lining of the tubes is to transport the egg into the uterine cavity after ovulation thus making it likely that exfoliated cells from STICs can be found in the uterine cavity. A promising approach for the detection of STICs has been established by Paul Speiser and Robert Zeillinger (Molecular Oncology Group, Department of General Gynaecology and Gynaecologic Oncology, Medical University of Vienna, Austria). This approach is called the ALPINE technique (Austrian Lavage Procedure for the Detection of tubal Intraepithelial Neoplasms) (manuscript under preparation). To facilitate an quick and easy lavage of the uterine cavity and proximal tubes, a special catheter was developed (MEDICOPLAST, MF 13005, catheter for uterine and tubal lavage). The ALPINE technique includes a lavage of the uterine cavity and proximal fallopian tubes and subsequent analysis of this lavage fluid for the presence of pre-malignant and malignant cells. For the proof of principle that tumor cells from ovarian cancer are shed and can be found in the lavages of the uterine cavity, uterine lavages were collected before a surgical intervention for suspected ovarian malignancy at our institution and at the Catholic University Leuven, Division Gynaecological Oncology, Belgium. After malignancy was confirmed, genetic changes in the TP53 and KRAS genes were determined in tumor tissue. In a set of 9 epithelial ovarian cancer patients (EOC) and 1 ovarian metastases of a signet ring carcinoma, the presence of these genetic changes was examined in lavage samples, using digital droplet PCR (ddPCR). 10 genetic changes were identified in tumor tissue of these patients and 9/10 (90%) of these changes were detected in the corresponding lavage specimen too. Furthermore, a filter approach, followed by p53 immunofluorescence staining was established, confirming the presence of tumor cells in the lavage sample of one additional patient. In a next step, lavage samples of 23 ovarian carcinoma patients, and if applicable corresponding tumor tissue, were analysed through deep sequencing by the group of Bert Vogelstein (Johns Hopkins University, Baltimore, USA). The presence of genetic changes, indicative for ovarian cancer, could be confirmed in 18/23 (78.3%) lavage specimen including both, early and advanced stages. These results are proof that ovarian cancer cells are shed into the fallopian tubes and uterine cavity, and can be collected through our ALPINE technique. The fact that ovarian cancer cells were detected with high sensitivity in the lavage of the uterine cavity and proximal tubes shows that this approach has potential in early diagnosis. Therefore, the investigators are confident that this method could be applied in detection of premalignant changes in high risk patients, as well. Aim of the study: The current study aims at answering the scientific question, whether exfoliated cells from STICs get transported into the uterine cavity via the fallopian tube, and whether it is possible to detect those cells in the lavage fluid from the uterine cavity and proximal fallopian tubes. Methods: To address this question, the investigators will study 20 lavage samples and their 20 corresponding STIC-positive tissue samples in women who opt for rrBSO because of increased risk of HGSC (mostly carrying a BRCA mutation), without a history of tubal occlusion for sterilization. Women who opt to have the fallopian tubes removed but the ovaries preserved are eligible for the study too, as are women who opt for rrBSO plus hysterectomy. More |
NCT01044186 :
A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity
(Completed) Locations: Oakland, United States, Orange, United States, Boston, United States, Jamaica, United States, New York, United States, New York, United States... Oakland, United States, Orange, United States, Boston, United States, Jamaica, United States, New York, United States, New York, United States, Cincinnatti, United States, Houston, United States, Athens, Greece, Ancona, Italy, Brindisi, Italy, Cagliari, Italy, Cosenza, Italy, Florence, Italy, Milan, Italy, Modena, Italy, Napoli, Italy, Torino, Italy More Study Dates: Start: June 1, 2003 Study Overview: No description available. No description available. |
NCT00155896 :
Establishing the Incidences of BRCA1 and BRCA2 Mutation by Combining DHPLC and Direct Sequencing in Ovarian Cancer
(UNKNOWN) Locations: Taipei, Taiwan Taipei, Taiwan Study Dates: Start: January 1, 2003 Study Overview: Malignancy is the first cause of death in Taiwan. There are around 30,000 people died due to malignancy every year. Ovarian cancer is the first mortality rate of gynecologic malignancies. The... Malignancy is the first cause of death in Taiwan. There are around 30,000 people died due to malignancy every year. Ovarian cancer is the first mortality rate of gynecologic malignancies. The incidence of ovarian cancer increased in recent 10 years. Ovarian cancer indeed is a disease that should be respected, however, there were only few of research work focusing on it in Taiwan. To study the mechanisms of carcinogenesis of ovarian cancer will help us understand this disease and develop new strategies of diagnosis and prevention for ovarian cancer in the future. The present diagnostic methods of malignancy are clinical symptoms, physical examination, evaluation of tumor markers and instruments. It is a important issue to diagnose cancer earlier to improve the survival of cancer patients. By the development of biomedical science, many genes have been identified to be related with the carcinogenesis. If we can detect the possibility of genetic mutation earlier, we may deal with the suspected areas of malignancy as soon as possible. To our present knowledge, carcinogenesis of ovarian cancer has strong correlation with some special genes such as BRCA1 and BRCA2 genes. There is 1 out of 200 normal population with BRCA1 or BRCA2 gene mutation in the western countries. The incidences of BRCA1 or BRCA2 gene mutation even increase to 30-50% in the population of familial ovarian cancer. Women with BRCA1 gene mutation have 80% to get breast cancer before the age of 70 and 63% of them would get ovarian cancer before the age of 70. Women with BRCA2 gene mutation have 80% to get breast or ovarian cancer before the age of 70. It seems that the genetic diagnosis of BRCA1/BRCA2 has its clinical practice. The development of new instrument- denaturing high-performance liquid chromatography (DHPLC) is to use automated detection to find out the minute or single mutation of nucleotide. It has been applied to the clinical service by utilizing DHPLC for the genetic diagnosis of BRCA1 and BRCA2 of breast cancer patients in the department of Genetic Medicine of our hospital. It will become a most powerful tool to establish the database of BRCA1 or BRCA2 gene mutation of the ovarian cancer patients in Taiwan, when we can use the technique of DHPLC combining with the direct DNA sequencing. So we propose this research project. There are two main purposes in this project. First, we will utilize the new technique of DHPCL with direct DNA sequence to set up the database of BRCA1 and BRCA2 gene mutation of ovarian cancer patients in Taiwan. We can screen out BRCA1 and BRCA2 gene mutation from high-risk group by this new technique. And then we can provide these patients suitable genetic consulting and related treatment planning. Second, we would lie to set up the new technique of DHPLC combining with direct DNA sequencing in the genetic diagnosis of ovarian cancer patients for the future clinical service in our hospital. More |
NCT01339650 :
Study of ABT-767 in Subjects With Breast Cancer 1 and Breast Cancer 2 (BRCA 1 and BRCA 2) Mutations and Solid Tumors or High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
(Completed) Locations: Groningen, Netherlands, Nijmegen, Netherlands, Rotterdam, Netherlands Groningen, Netherlands, Nijmegen, Netherlands, Rotterdam, Netherlands Study Dates: Start: May 6, 2011 | Actual Completion Date: November 30, 2017 Study Overview: This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced BRCA1 or BRCA2-mutated solid tumors and high grade... This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced BRCA1 or BRCA2-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer. ABT-767 is a potent oral inhibitor of the enzymes poly (ADP-ribose) polymerase 1 and 2 (PARP-1 and PARP-2). Malignancies with deficiencies in homologous repair, such as BRCA-1 and BRCA-2 deficient tumors, are more dependent on PARP for deoxyribonucleic acid (DNA) repair than normal cells and, thus, are thought to be more sensitive to PARP inhibition. The study design is a single-arm dose escalation study to determine dose-limiting toxicities, maximum tolerated dose and the recommended Phase 2 dose (RPTD) of orally administered ABT-767 in subjects with BRCA mutations and malignancies. In order to further evaluate the safety and tolerability of ABT-767 at the RPTD, 20 additional subjects will be enrolled in an expanded safety cohort consisting of BRCA1- or BRCA2-mutated Breast cancer and Ovarian cancer. |
NCT00419510 :
Genetic Counseling in African American Women
(Completed) Locations: Philadelphia, United States Philadelphia, United States Study Dates: Start: February 1, 2003 | Actual Completion Date: September 1, 2012 Study Overview: Five to 10% of all breast cancer cases have been attributed to two breast ovarian cancer susceptibility genes called BRCA1 and BRCA2 (BRCA1/2). Genetic counseling and testing for BRCA1/2 mutations is... Five to 10% of all breast cancer cases have been attributed to two breast ovarian cancer susceptibility genes called BRCA1 and BRCA2 (BRCA1/2). Genetic counseling and testing for BRCA1/2 mutations is now available through clinical research programs using standard counseling protocols. The goal of pre test counseling is to facilitate informed decision making about whether to be tested and to prepare participants for possible outcomes. The goal of post test counseling is to provide information about risk status, recommendations for surveillance, and options for prevention. However, previous research suggests that African American and Caucasian women differ in their attitudes about and responses to pre test education and counseling. Increasingly, cultural beliefs and values are being recognized as important factors in genetic counseling. Despite recommendations to increase the cultural sensitivity of breast cancer risk counseling, such programs have not been developed or evaluated. Therefore, the purpose of this study is to develop a Culturally Tailored Genetic Counseling (CTGC) protocol for African American women and evaluate its impact on psychological functioning and health behaviors compared with Standard Genetic Counseling (SGC) in a randomized clinical trial. 1. To evaluate the relative impact of CTGC vs. SGC on decision making and satisfaction about BRCA1/2 testing. Compared to SGC, CTGC will lead to higher rates of test acceptance and satisfaction with testing decisions. These effects will be mediated by increases in perceived benefits and decreases in perceived limitations and risks of genetic testing.
2. To evaluate the impact of CTGC vs. SGC on quality of life and health behaviors following BRCA1/2 testing. Compared to SGC, CTGC will lead to larger decreases in general and cancer specific distress, greater increases in adherence to cancer screening guidelines, and lower rates of prophylactic surgery. Reductions in psychological distress will be mediated by increased use of spiritual coping strategies. Secondary Aim To identify African American women who are most and least likely to benefit from CTGC vs. SGC. We predict that the relative benefits of CTGC will be greatest for women with greater endorsement of African American cultural values and those identified as BRCA1/2 carriers. More |
NCT04437771 :
Long-Term Follow-up of Subjects With Fanconi Anaemia Subtype A Treated With ex Vivo Gene Therapy
(Enrolling by Invitation) Locations: Madrid, Spain Madrid, Spain Study Dates: Start: June 1, 2020 | Estimated Completion Date: January 30, 2035 Study Overview: This long-term follow-up protocol will evaluate the long term safety and efficacy of the infusion of autologous CD34+ cells transduced with lentiviral vector (LV) carrying the FANCA gene. This long-term follow-up protocol will evaluate the long term safety and efficacy of the infusion of autologous CD34+ cells transduced with lentiviral vector (LV) carrying the FANCA gene. |
NCT00352976 :
TBI Dose De-escalation for Fanconi Anemia
(Completed) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: May 18, 2006 | Actual Completion Date: October 9, 2020 Study Overview: Study Treatment: Patients will receive voriconazole (antifungal therapy) by mouth beginning 1 month prior to conditioning therapy, if possible. 1) The subject is to receive total body irradiation... Study Treatment: Patients will receive voriconazole (antifungal therapy) by mouth beginning 1 month prior to conditioning therapy, if possible. 1) The subject is to receive total body irradiation (300 cGy) with thymic shielding; it will be given six days before the stem cells are given (day -6). 2) Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine and Cyclophosphamide via central line (i.e. Hickman or Broviac). Starting Day -3, patients will receive sirolimus therapy with a taper commencing on day +180 and also mycophenolate mofetil (MMF) through day +30 or for 7 days after engraftment, whichever day is later, if no acute graft-versus-host disease (GVHD). 4) If the subject is receiving bone marrow or "peripheral" stem cells (cells collected from the donor's arm via a cell separator), on the day of transplantation, the stem cells taken from the donor will be put into a machine which will separate the lymphocytes (the cells that cause graft-versus-host disease \[GVHD\]) from the stem cells. If the subject is receiving an umbilical cord blood, the lymphocytes will not be removed because the risk of GVHD is not as high. Otherwise all patients will receive the same treatment. The stem cells are given as an infusion into the subject's existing catheter over 1-2 hours on day 0.5. On the day after transplant (day +1) subjects will be given G-CSF to stimulate the growth of the transplanted cells. 6. While receiving treatment and until the subject's blood counts recover he/she will have daily blood tests, and several bone marrow biopsies and aspirates. After recovery, subjects will be seen once a month for a health assessment and blood tests until at least 3 months after the cells have been infused. Additional blood tests or assessments may be done as medically indicated. |
NCT00479115 :
Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and AMD3100
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: May 1, 2007 | Actual Completion Date: December 1, 2010 Study Overview: Fanconi anemia is a rare autosomal recessive syndrome comprised of progressive bone marrow failure, congenital anomalies and a predisposition to malignancy. The heterozygote rate in the United States... Fanconi anemia is a rare autosomal recessive syndrome comprised of progressive bone marrow failure, congenital anomalies and a predisposition to malignancy. The heterozygote rate in the United States may be as high as 1 in 300. The mean age for the onset of aplastic anemia is approximately eight years. Although improved supportive care has prolonged the survival of these patients from only a few years from the diagnosis of bone marrow failure, the mean age of death is still approximately 24 years of age. Most patients die from complications of bone marrow failure including bleeding, or infection, or from malignancy or complications of stem cell transplantation. In a recent 20 year review of patients in the Fanconi anemia registry, the actual risk of developing leukemia or other cancers was approximately 30%. The diagnosis of Fanconi anemia initially rested upon finding the combination of bone marrow failure with congenital anomalies. These anomalies include cafe au lait spots and/or hypo pigmentation of the skin, short stature, upper limb malformations (often involving the thumb or radius), renal and gastrointestinal abnormalities, microcephaly, and characteristic facies with a broad nasal base, epicanthal folds, narrow set and small eyes and micrognathia. The bone marrow failure is characterized by slow progression to severe bone marrow aplasia and pancytopenia, stress erythropoiesis with fetal features including macrocytosis, elevated hemoglobin F, and i antigen expression. Attempts to culture bone marrow progenitors in vitro from patients with Fanconi anemia demonstrates decreased numbers of myeloid and erythroid colonies (CFU) consistent with clinical bone marrow failure. Fanconi anemia cells appear to have a defect in DNA repair that leads to increased spontaneous chromosomal breakage. This feature increases the susceptibility of Fanconi anemia cells to DNA bifunctional cross-linking agents such as mitomycin C and diepoxybutane (DEB). The diagnosis of Fanconi anemia now relies upon detecting increased chromosomal breakage after in vitro treatment with DEB. 11 Similarly, cells cultured from patients with Fanconi anemia display increased susceptibility to the cytotoxicity of mitomycin C. More recently, cells from patients with Fanconi anemia have been demonstrated to display G2 phase prolongation/arrest, increased sensitivity to toxicity by oxygen, defective p53 induction and increased apoptosis. Fanconi anemia can be classified into at least thirteen complementation groups by somatic cell hybrids. The complementation is based upon correction of the chromosomal sensitivity to cross-linking agents in hybrid cells. Twelve independent genes have been cloned and characterized within these 13 complementation groups. A loss of function in any of these genes including FANC A, B, C, D2, E, F, G, J, L, M, N, and FANC D1 (which is BRCA2) can cause Fanconi anemia. However, complementation groups A, C, and G account for approximately 80-85% of patients with Fanconi anemia in the United States. Discrete mutations in these genes have been identified in families with the disorder. Expression of the complementary cDNA gene in the respective Fanconi anemia cells in vitro corrects the increased chromosomal breakage from DEB and the increased sensitivity to mitomycin C. Expression of gene products in bone marrow progenitors from patients with Fanconi anemia increases survival in in vitro assays. The current treatment for Fanconi anemia relies upon hematological support in the form of red blood cell and platelet transfusions. Aplastic anemia will transiently respond to androgen therapy in 50% of children. G-CSF has also been utilized in published studies from our own group to improve the number of myeloid cells in the peripheral circulation. Bone marrow transplantation has cured some patients of their bone marrow failure; however, there appears to be more toxicity to the conditioning regimens and there may be increased numbers of solid tumors post transplant compared to patients without the disorder. Survival five years after a matched sibling transplant now exceeds 65% and after an unrelated donor transplant 30%. More recent studies in unrelated donor transplant for Fanconi anemia at Cincinnati Children's Hospital and the University of Minnesota have reported survival rates approaching those observed in matched sibling donor transplants. However, graft failure resulting in death remains a major obstacle. The availability of sufficient numbers of (previously purified and cryopreserved) autologous HSC for re-infusion after graft failure may prevent this complication. Finally, gene therapy approaches are being pursued, but to date, there is no evidence for cure with this approach in humans, although correction has been reported in murine models. These studies are hampered by the fact that mouse knockouts of FA genes do not develop spontaneous aplastic anemia and thus are not phenocopies of the human disease. Thus in previously reported mouse-studies, gene therapy approaches required ablative total body irradiation of the recipient mice to ensure engraftment of the gene corrected stem cells. An obvious limitation of Fanconi anemia hematopoietic stem cell gene transfer is that the necessary target for genetic manipulation, the hematopoietic stem cell (or its surrogate, CD34+ cell) is progressively lost during the development of aplastic anemia. Thus at the time of severe aplasia and the greatest need for treatment, target stem cells for genetic modification are deficient. Collection of a meaningful number of HSC prior to the onset of aplastic anemia for eventual use in a therapeutic gene therapy trial will be explored in the study outlined here. Key questions remaining are whether corrected HSC from Fanconi anemia patients will engraft after autologous re-infusion without any cyto-reductive treatment of the recipient and, if engrafted, whether the corrected cells will demonstrate a proliferative advantage over uncorrected stem cells. More |
NCT04069533 :
Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
(Active, Not Recruiting) Locations: Madrid, Spain, London, United Kingdom Madrid, Spain, London, United Kingdom Study Dates: Start: November 28, 2019 | Estimated Completion Date: February 1, 2025 Study Overview: This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector... This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in pediatric subjects with FA-A. Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning. More |
NCT00165152 :
Counseling Interventions for BRCA 1/2 Cancer Susceptibility Testing
(Completed) Locations: Boston, United States, Boston, United States Boston, United States, Boston, United States Study Dates: Start: July 1, 1998 | Actual Completion Date: June 1, 2005 Study Overview: * Patients will have a blood sample drawn that will be analyzed for altered BRCA1 or BRCA2 genes. An alteration of BRCA1 or BRCA2 gene means there is an increased risk of developing breast and... * Patients will have a blood sample drawn that will be analyzed for altered BRCA1 or BRCA2 genes. An alteration of BRCA1 or BRCA2 gene means there is an increased risk of developing breast and ovarian cancer.
* Patients participating in this study have either: 1) expressed an interest in testing for an underlying genetic factor that may account for the breast or ovarian cancer in their family; 2) have at least one relative that has been found to have a BRCA1 or BRCA2 alteration; 3) have a personal or family history of breast or ovarian cancer that is suggestive of a BRCA1 and BRCA2 alteration; or 4) has breast or ovarian cancer, or has at least one close relative with a history of breast or ovarian cancer and are a member of an ethnic group with increased frequency of BRCA1 and BRCA2 alterations.
* Patients will be randomized into one of two counseling groups. Two visits with a specially trained genetic counselor or nurse in conjunction with a medical oncologist and/or a medical specialist will be done in which information will be given either about genetic counseling or enhanced informed consent. These visits will be audio-taped to monitor how the project staff is covering the important information about testing.
* Throughout this study patients will be asked to complete questionnaires and psychological measures. These forms will be completed before and after the first visit, and a subset of them again at 2-4 weeks after the second visit, and at 4, 6, and 12 months.
* In addition 30 women will be asked to complete a 20-30 minute telephone interview with the program psychologist. |
NCT06490510 :
Prognostic Significance of Mutation Type and Chromosome Fragility in Fanconi Anemia
(Completed) Locations: Barcelona, Spain Barcelona, Spain Study Dates: Start: May 16, 2024 | Actual Completion Date: June 18, 2024 Study Overview: No description available. No description available. |
NCT03050268 :
Familial Investigations of Childhood Cancer Predisposition
(Recruiting) Locations: Memphis, United States Memphis, United States Study Dates: Start: April 6, 2017 | Estimated Completion Date: March 31, 2037 Study Overview: During the study, blood samples or other healthy tissue will be obtained from participants, as well as medical and family histories. When possible, leftover tumor samples will also be collected. If... During the study, blood samples or other healthy tissue will be obtained from participants, as well as medical and family histories. When possible, leftover tumor samples will also be collected. If participants agree to be re-contacted in the future, they will be asked about once each year to update their health information and family history. A blood sample will be drawn at St. Jude or at a convenient place of the participant's choice. Saliva collection will be obtained if a blood draw is not possible. For participants who are present at St. Jude, saliva collection will generally be performed only once using a saliva collection kit. However, if the first collection is not sufficient for protocol required studies, then additional saliva samples may need to be collected, for up to a total of 5 occurrences. For non St. Jude participants, or participants who do not wish or cannot come to St. Jude, saliva will be collected locally and shipped back to the St. Jude. A skin sample will be performed as a source of germline DNA from participants who have undergone an allogeneic bone marrow transplant and do not have a source of pre-transplant DNA available. A skin sample will only be obtained one time. The biological samples will be stored in the St. Jude Biorepository. The DNA of the samples will be studied to determine if there are changes in specific genes that might explain the cancers in the participant or their family members. When available, and if consent is given by the participant, previously collected and stored leftover tumor samples, bone marrow samples or stored DNA may be analyzed. Genetic variants of interest include: 1) mutations in known genes that may have escaped detection through prior clinical genetic testing; 2) coding mutations predicted to disrupt protein function, particularly in genes and pathways known to be associated with cancer; 3) potential mutations in regulatory regions of the genome, as predicted by epigenetic studies. In some cases, individuals with known predisposing mutations exhibit milder, more severe or atypical phenotypes. Family members who harbor a predisposing mutation but are discordant for a cancer phenotype will be selected for cellular and genetic studies. These will include DNA sequencing and possibly also creation and analysis of induce pluripotent stem cells (iPSC), transcriptome or epigenetic analysis. All samples will be identified by a code after removal of all personal identifiable information. Samples will remain in the repository for current and future study. More |
NCT01995305 :
Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents
(AVAILABLE) Locations: Tianjin, China Tianjin, China Study Dates: Start: Not available Study Overview: Heterogeneity of FA. In the research of animal model, the phenotypes of FANCA, FANCC and FANCG knockout mice are similar. They grow up and develop normally, without any severe blood disease or tumor.... Heterogeneity of FA. In the research of animal model, the phenotypes of FANCA, FANCC and FANCG knockout mice are similar. They grow up and develop normally, without any severe blood disease or tumor. However, they show chromosome instablity and highly sensitivity to MMC. And they have gonadal dysfunction and fertility defects. From this we conclude that the severe physical deformity of FA patients might be induced by other mutations. By comparing among the FA patients and between FA patiens and normal people, we look forward to find the mutated genes and verify their relationship with the physical deformity. Even in 90% of FA patients the bone marrow failure will eventually occur, but the starting age ranges from 8-84. And Immuno-inhibition therapy has no effects on FA. Other DNA repair dysfunction diseases have higher rate of tumor, but not so high rate of bone marrow failure as FA does, which implies that the FA protein has the key role in hematopoietic stem cell maintainance. In FancC-/- mice, young mice is insensitive to DNA crosslinks with comet assay, but not adult mice, indicating that the accumulation of DNA damage during time leads to DNA repairment defects. by comparing the exome of FA patients and their parents, the mutations that were accumulated in FA patients could be found, and these genes might be sensitive to repairment and be important for hematopoiesis maintainance. More |
NCT04038502 :
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer
(Recruiting) Locations: West Los Angeles, United States, Aurora, United States, Washington D.C., United States, Bay Pines, United States, Orlando, United States, Decatur... West Los Angeles, United States, Aurora, United States, Washington D.C., United States, Bay Pines, United States, Orlando, United States, Decatur, United States, Boise, United States, Chicago, United States, Ann Arbor, United States, Minneapolis, United States, Kansas City, United States, New York, United States, The Bronx, United States, Durham, United States, Portland, United States, Philadelphia, United States, Seattle, United States, Madison, United States More Study Dates: Start: October 1, 2019 | Estimated Completion Date: August 31, 2027 Study Overview: Study General Trial Over-view Study General Trial Over-view This study is designed to help better understand treatment options compared to standard therapies for patients who have targeted DNA repair mutations and metastatic castrate resistant prostate cancer (mCRPC). Cancer therapies are aimed at finding a way to kill the cancer cells while causing minimal damage to normal (non-cancer) cells. This often works because cancers cells grow faster than many normal cells, many treatments are aimed at to take advantage of that difference. One of the ways to do this is to damage the DNA of these more rapidly growing cells. However, if the cells have a way of repairing that damage then therapies may not work as well. Some research shows that when specific changes or mutations occur in the genes involved with repairing DNA damage, resulting cancers have responded well to drugs which damage DNA. Olaparib is known as a PARP inhibitor and is standard of care therapy for men with BRCA altered mCRPC. Carboplatin is a synthetic antineoplastic agent which has been used in the treatment of solid tumors and BRCA related cancers. When mutations occur in critical DNA-repair genes, research has found that treatment with carboplatin is also effective. This research is being done to determine the response of mCRPC in patients with DNA repair mutations to treatment with olaparib compared to carboplatin. This study will test whether giving one drug or the other a has a better response. Patients wishing to participate in this study are screened for safety and health eligibility before enrolling. This study is enrolling 100 male participants total, from across the VAMC nationally who have the following: * Metastatic castration-resistant prostate cancer (mCRPC)
* Cancer that has gotten worse, after any number of first-line treatments
* Mutations in DNA-repair genes discovered as part of a patient's routine care. Once eligibility is determined, enrolled participants are randomized into one of two groups: * Group A will start with carboplatin (IV) first, given every 21 days, then have the option to switch to the second treatment with olaparib taken daily, (orally) with cycles of every 28 days.
* Group B will start with olaparib first, taken (orally), with 28 day cycles, then have the option to switch to the second treatment with carboplatin (IV) every 21 days. Both study drugs in this trial are currently FDA approved, and are prescribed at the participating VAMC clinical sites per institutional guidelines. Carboplatin given in IV is also given as prescribed at the participating VAMC, and administered per institutional guidelines. Participants are monitored for health and body function, cancer progression, toxicity and life quality at every visit during the trial and at an end of treatment visit (28 days after completion of the trial or after withdrawal). For participants who respond well to treatment during the trial, additional treatment cycles may be added and the study can be extended. Participants who experience intolerable toxicity, cancer progression, or whose doctors decide to change treatment, will either be switched to the opposite study drug or withdrawn from the study. This important trial is designed to compare response rate and duration of response using carboplatin compared to olaparib in patients who have mCRPC which contains DNA repair gene mutations. More |
NCT04042831 :
Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations
(UNKNOWN) Locations: Scottsdale, United States, Jacksonville, United States, Boston, United States, Rochester, United States, New York, United States, Houston, United States Scottsdale, United States, Jacksonville, United States, Boston, United States, Rochester, United States, New York, United States, Houston, United States Study Dates: Start: June 24, 2020 Study Overview: PRIMARY OBJECTIVES: PRIMARY OBJECTIVES: I. To determine the efficacy (progression free survival \[PFS\] rate at first scan) of olaparib monotherapy in advanced biliary tract cancer (BTC) with mutations in deoxyribonucleic acid (DNA) repair genes. SECONDARY OBJECTIVES: I. To determine the overall survival of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib. II. To determine the progression free survival of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib. III. To determine the objective response of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib. IV. To assess the duration of response for patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib who experience an objective response. V. To assess the frequency and severity of adverse events in advanced biliary tract cancer patients treated with olaparib. CORRELATIVE RESEARCH OBJECTIVES: I. Determine the prevalence of mutations including those targeting DNA repair pathways. II. Identify mutational signatures associated with pathogenic process in advanced biliary tract cancer samples. III. Correlate the presence of mutations and mutational signatures linked to mutations in DNA repair genes and homologous recombinant repair with clinical responses to olaparib. IV. To evaluate putative biomarkers related to: Iva. De novo sensitivity. IVb. Tumor evolution and resistance, to PARP inhibition from olaparib in BTC. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) throughout the trial, and collection of blood and tissue samples on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 3 years. More |
NCT01565005 :
Microcephaly Genetic Deficiency in Neural Progenitors
(Completed) Locations: Paris, France Paris, France Study Dates: Start: October 1, 2013 | Actual Completion Date: December 1, 2017 Study Overview: Phenotyping study on 2 different cohorts of rare disease affected patients: Phenotyping study on 2 different cohorts of rare disease affected patients: * Group1: MCPH (including different MCPH subtypes)
* Group2: Fanconi Anemia (with or without microcephaly) Inclusion criteria: Common to each group: * Age \> 3 years
* Access to french "Social Security"
* No contraindication for MRI Group1: * Primary microcephaly without gross malformation within or extra nervous central system
* OFC \< -2SD at birth and \< -3 SD after age 6months
* Mutation in one MCPH gene Group2: Proven Fanconi Anemia with: * Positive chromosome breakage blood test
* One of the 3 following elements: FANCD2 positive test Fibroblast sensitivity to mitomycin Mutation in one FANC gene Control subjects: * No antecedent
* Normal education Aims: 1. Description of neurological, neuropsychological and radiological phenotype for each group
2. Phenotype comparison: * groups 1\&2
* group1 or 2 with control subjects
* different MCPH subtypes within group1
* with or without microcephaly within group2
3. Epidemiological data on these rare diseases in our population Protocol: Patients from both groups and control subjects will be evaluated in CIC for 1 day ½. They will be examined by a child neurologist and a geneticist. All of them will have cranial MRI (1.5Tesla). Neuropsychological assessment will be performed (Wechsler scales) for patients and control subjects. More |
NCT03344965 :
Olaparib In Metastatic Breast Cancer
(Active, Not Recruiting) Locations: Birmingham, United States, San Francisco, United States, Chicago, United States, Indianapolis, United States, Baltimore, United States, Boston... Birmingham, United States, San Francisco, United States, Chicago, United States, Indianapolis, United States, Baltimore, United States, Boston, United States, Boston, United States, Boston, United States, Basking Ridge, United States, Middletown, United States, Montvale, United States, Commack, United States, East White Plains, United States, New York, United States, Uniondale, United States, Durham, United States, Erie, United States, Philadelphia, United States, Pittsburgh, United States, Seattle, United States More Study Dates: Start: April 1, 2018 | Estimated Completion Date: December 30, 2025 Study Overview: * This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific... * This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the study drug, Olaparib, is being studied for use in this setting and the research doctors are trying to learn more about it-the side effects it may cause and if the drug is effective in treating this type of cancer.
* What is a DNA repair gene mutation? \-- In order to survive, all cells, even cancer cells, must be able to repair their genetic material (DNA) when it gets damaged. A mutation is an alteration or change in a gene- either inherited from a parent or acquired over time- that prevents the gene from working properly. Faulty genes (or genes that carry a mutation) have been linked to increased risk of hereditary breast and ovarian cancer.
* What is Olaparib? * Olaparib is a drug that may stop cancer cells from growing. Olaparib is a PARP inhibitor which means that it blocks an enzyme (proteins that help chemical reactions in the body occur) in cells called PARP. PARP helps repair DNA when it becomes damaged. It has been shown that the tumors in individuals who have inherited or acquired a mutation in the BRCA1 or BRCA2 genes are often sensitive to killing by PARP inhibitors.
* In normal cells and many other tumors, repair of damage to the DNA requires pathways of genes that work with BRCA1 and BRCA2. Therefore, when a drug that inhibits PARP from working is given to people with a BRCA mutation, or a defect in another gene that works with BRCA1 and BRCA2, both ways of repairing damaged DNA no longer work. The combined effect of knocking out both DNA repair mechanisms is so severe that the cancer cells could die. This might stop the growth of type of breast cancer, but this is not known.
* The FDA (U.S. Food and Drug Administration) has approved Olaparib for use in advanced ovarian cancer with a BRCA1 or BRCA2 mutation. Olaparib is not approved for breast cancer. More |
NCT01720147 :
Quercetin in Children With Fanconi Anemia; a Pilot Study
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: July 1, 2012 | Actual Completion Date: October 26, 2021 Study Overview: Current therapies for children with Fanconi anemia (FA) and bone marrow failure, i.e. androgens or bone marrow transplantation, are associated with significant morbidity and mortality. Current therapies for children with Fanconi anemia (FA) and bone marrow failure, i.e. androgens or bone marrow transplantation, are associated with significant morbidity and mortality. This is a pilot study aiming to assess feasibility, toxicity and pharmacokinetics of oral Quercetin therapy in patients with FA. This is a first step towards a clinical study of the efficacy of Quercetin therapy in delaying progression of BMF in FA. Additional correlative studies will include assessment of impact of Quercetin on reduction of Reactive Oxygen Species (ROS), maintenance or improvement of hematopoietic stem cell (HSC) reserve, improvement of hematopoiesis (i.e. peripheral counts) and insulin sensitivity/glucose tolerance. This study is an open-label single arm study. Funding Source - FDA OOPD Accrual closed for the main study. Expansion cohort added to observe additional patients at the desired dose. Expansion Cohort: The second and third cohort of participants completed the study treatment as expected, tolerating Quercetin well without any DLT. Based on the PK and ROS analyses, the dose was increased for the fourth cohort (subjects #10-12). To observe additional patients at the desired dose, an expansion cohort is being added. Up to 20 patients will be enrolled in the expansion cohort. The purpose of the expansion cohort is to assess the effects of quercetin supplement at the desired dose on clinical and biological endpoints. Patients in the expansion cohort will receive quercetin treatment for the first 26 weeks. Patients will be able to continue quercetin supplement after the completion of the study period of 26 weeks if they wish. If patients decide to continue quercetin after the first 26 weeks, quercetin will be provided by the investigational pharmacy for up to 1 year. Patients who continue quercetin supplement after 26 weeks, but discontinue quercetin before 1 year will be followed through the 1 year visit. Patients who discontinue quercetin supplement any time after the 1 year visit will be followed through the 2 year visit. Patients previously enrolled in the initial phase of the study (cohorts 1-4) may be considered for enrollment on the expansion cohort of the study provided they meet all inclusion and exclusion criteria. More |
NCT05687149 :
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
(Recruiting) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: March 23, 2023 | Estimated Completion Date: December 31, 2035 Study Overview: Study Description: Study Description: This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of medical records, and cancer surveillance. A prospective cohort of individuals with Fanconi anemia (FA) at very high risk of squamous cell carcinoma (SCC) will be screened and provide new information on oral potentially malignant lesion (OPML) development and robustly quantify the risk of progression of OPML to cancer in FA. Objectives: Primary Objectives: 1. To establish a central program and a team of expert clinicians and scientists at the NIH Clinical Center to conduct a comprehensive longitudinal study of cancer screening in adolescent and young adults (AYA) with FA at high risk of SCC through detailed clinical evaluation and biospecimen collection.
2. To characterize the clinical and pathological natural history of OPMLs in AYAs with FA using brush biopsies for cytopathologic diagnosis and DNA aneuploidy and correlate those findings with tissue biopsies and genomic analyses of oral epithelial dysplasia (OED) and SCC.
3. To prospectively screen individuals with FA for early indicators for the development of esophageal and anogenital SCC and hematological malignancy. Secondary Objectives: 1. To identify genetic, epigenetic, and immunologic mechanisms underlying tumorigenesis and immune escape in individuals with FA.
2. To facilitate the enrollment of individuals with FA with high-grade dysplasia or SCC in intra- and extra-mural precision intervention trials. Endpoints: Primary Endpoints: 1. Characterize the natural history of OPMLs in FA, rates of progression, regression, and development of new lesions
2. Determine the utility of brush biopsy to identify oral dysplasia and SCC in FA
3. Identify potential precursor states for esophageal and anogenital cancers in FA
4. Develop screening guidelines for esophageal and anogenital cancer in FA Secondary Endpoints: 1. Identify predictive biomarkers of oral SCC development
2. Characterize genetic and epigenetic changes that lead to SCC development
3. Facilitate patient enrollment in intervention trials More |
NCT01001598 :
Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
(Terminated) Locations: Boston, United States Boston, United States Study Dates: Start: November 1, 2009 Study Overview: Eligible patients with either Fanconi anemia (FA) or Dyskeratosis congenita (DC) will initially receive danazol at a dose of 5 mg/kg/d orally, rounded to the nearest 100 mg. For the first 8 weeks,... Eligible patients with either Fanconi anemia (FA) or Dyskeratosis congenita (DC) will initially receive danazol at a dose of 5 mg/kg/d orally, rounded to the nearest 100 mg. For the first 8 weeks, the patient will be evaluated at weeks 2, 5, and 8 for hematologic response (HR). If the patient shows a hematological response (either a hemoglobin or platelet value no longer meeting blood cell count criteria for protocol inclusion in the absence of recent transfusions)within the first 12 weeks on the initial dose, the study drug will be continued at this dose for the next 6 weeks. If the patient fails to show any hematologic response within the first 12 weeks, the dose will be escalated to 10 mg/kg/day for the next 6 weeks, and an additional monitoring visit will be required at week 14. If at week 18, the patient fails to show any hematological response on the increased dose, the dose will be increased to 15 mg/kg/day for another 6 weeks (not to exceed 800 mg/day), and an additional monitoring visit will be required at week 20. At 24 weeks, if there is no response to this dose the patient will be taken off study drug and classified as a treatment failure, and will be monitored at weeks 38 and week 52). After week 24, if the patient continues to show a response, however, the study drug may be continued at the discretion of their primary care physician, with monitoring at weeks 38 and 52. Should the patient lose the hematologic response on 5 or 10 mg/kg/day dosing at any point within the first 18 weeks of treatment, the dose will be escalated to 10 or 15 mg/kg/day (not to exceed 800 mg/day), respectively. The patient will continue to be evaluated at the next visit. If after week 24 no hematologic improvement is seen, the patient is then taken off study drug and monitored at weeks 38 and 52. More |
NCT00899522 :
Tissue Sample Collection From Patients With Fanconi Anemia
(Completed) Locations: Portland, United States Portland, United States Study Dates: Start: August 1, 2005 | Actual Completion Date: May 1, 2013 Study Overview: OBJECTIVES: OBJECTIVES: * Acquire rare solid tumor samples from patients with Fanconi anemia in order to create a Fanconi Anemia Cell Repository at the Oregon Health and Science University Cancer Institute.
* Study repository tissue using a variety of molecular methods, including gene microarrays.
* Develop cancer cell lines that are publicly available from tissue archived from patients with Fanconi anemia. OUTLINE: Tumor biopsies are collected from patients with Fanconi anemia and archived for future molecular studies, cell line generation, and general usage by the research community at large. Medical information about the patient's cancer is also archived. PROJECTED ACCRUAL: Not specified. More |
NCT00004787 :
Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
(Completed) Locations: Not specified Not specified Study Dates: Start: December 1, 1994 Study Overview: PROTOCOL OUTLINE: Patients receive granulocyte colony-stimulating factor (G-CSF) subcutaneously every day for 8 weeks; nonresponders receive an increased dose for an additional 8 weeks. Patients who... PROTOCOL OUTLINE: Patients receive granulocyte colony-stimulating factor (G-CSF) subcutaneously every day for 8 weeks; nonresponders receive an increased dose for an additional 8 weeks. Patients who respond at week 8 or 16 are then tapered to a lower maintenance dose of G-CSF administered every other day through week 40. The dose is adjusted to maintain an absolute neutrophil count above 1500. Patients are removed from study for failure to achieve a complete response by week 16, unacceptable nonhematologic toxicity, the identification of a clonal karyotype in marrow, or the onset of leukemia. More |
NCT00243399 :
Oxandrolone for the Treatment of Bone Marrow Aplasia in Fanconi Anemia
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: July 1, 2004 | Actual Completion Date: January 1, 2010 Study Overview: The primary purpose of this study is to evaluate the safety of the drug oxandrolone in patients with Fanconi anemia (FA), and secondarily to determine if this drug can help in the treatment of bone... The primary purpose of this study is to evaluate the safety of the drug oxandrolone in patients with Fanconi anemia (FA), and secondarily to determine if this drug can help in the treatment of bone marrow failure in these patients. It is hoped that oxandrolone will have less side effects than oxymetholone, the androgen used most frequently in the short-term treatment of bone marrow failure in FA patients. Subjects will be enrolled for approximately 18 to 30 months (12 - 24 months of treatment and 6 months additional monitoring). The oxandrolone starting dose is 0.04mg/kg/day. Study monitoring includes weekly complete blood counts, monthly serum chemistry labs, quarterly physical examinations including virilization exams and liver ultrasounds. Semi-annually, hand radiographs are obtained for bone maturation and behavioral assessments are conducted to detect any aggressive behavior or mood changes. If no improvement n the subject's blood counts are noted after 4 months of therapy, the dose will be increased to 0.08mg/kg/day for a period of 4 more months. If no improvement is noted after a total of eight months, oxandrolone will be discontinued. If the blood counts show improvement, then the drug will continue for a minimum of twelve months. Subjects may remain on study and receive a total of 24 months of therapy if they have a response in their blood counts without unacceptable side effects. Post-treatment monitoring includes blood work and ultrasound every three months, and hand radiograph at six months. |
NCT06958380 :
Corrective Exercise and Rehabilitation in Fanconi Anemia: A Case Study
(Completed) Locations: Isfahan, Iran Isfahan, Iran Study Dates: Start: May 3, 2025 | Actual Completion Date: July 20, 2025 Study Overview: Fanconi anemia (FA), first described in 1927 by Dr. Guido Fanconi, is a rare, inherited, autosomal recessive disorder affecting proteins involved in DNA repair and cell cycle regulation. This... Fanconi anemia (FA), first described in 1927 by Dr. Guido Fanconi, is a rare, inherited, autosomal recessive disorder affecting proteins involved in DNA repair and cell cycle regulation. This syndrome is characterized by congenital malformations (involving the limbs, skeletal system, kidneys and urinary structures, sensory organs (eyes and ears) and central nervous system), progressive bone marrow failure (aplastic anemia), increased cancer incidence (particularly head/neck epithelial cancers and acute myeloid leukemia (AML)) and a range of physical anomalies (including microcephaly and short stature). Higher prevalence rates of FA have been observed in populations with a high incidence of consanguineous marriages, including South African Blacks, Turks, Saudi Arabians, Ashkenazi Jews and Iranians. Globally, the disorder affects approximately 1 in every 160,000 to 360,000 individuals, while the estimated carrier frequency is around 0.3%. FA results from mutations in at least 22 genes involved in genomic stability and DNA repair. The majority of FA-related changes-accounting for more than 80%-are found in the FANCA, FANCG, and FANCC genes, whereas alterations in the remaining genes are comparatively rare. The diagnosis of FA, though challenging due to variable expressiveness, relies on clinical suspicion confirmed through genetic analysis. FA should be suspected in cases of de novo bone marrow failure, especially in younger patients, or in the presence of spontaneous chromosomal breaks and certain cytogenetic abnormalities. Early diagnosis, while not currently improving cure rates, enables healthcare professionals to implement systematic follow-up protocols and timely interventions. Therapeutic management of FA relies on vigilant, risk adapted monitoring of hematologic status-complete blood counts and bone marrow assessments are scheduled from every six months to six weeks based on cytopenia severity-to detect dysplasia or clonal abnormalities. Supportive care with red cell and platelet transfusions, infection prophylaxis, and occasional androgen therapy helps maintain blood counts while preparing for hematopoietic stem cell transplantation (HSCT). Transplantation, preferably before transfusion dependence or emergence of poor risk cytogenetic changes, offers the only curative approach to marrow failure. Simultaneously, long term surveillance addresses FA's systemic complications through regular cancer screenings and organ specific evaluations. Despite the established role of physical and occupational therapy in managing skeletal abnormalities in FA, there is a notable scarcity of research specifically examining the effectiveness of structured exercise rehabilitation programs for this population. In a similar study, Ye et al. (2024) found that a structured exercise rehabilitation program improved quality of life, reduced fatigue, and enhanced physical performance in aplastic anemia patients undergoing HSCT. These promising outcomes support the potential benefit of a similar approach in Fanconi anemia patients. Based on the identified research gaps, the investigators hypothesize that a structured program of corrective exercise, physical therapy interventions, and rehabilitation will improve quality of life, physical function, and potentially influence hematological parameters in patients with Fanconi anemia. The primary objective of this case study is to evaluate the effectiveness of these interventions on patient-reported quality of life. Secondary objectives include assessing improvements in muscle strength, fatigue levels, functional independence in activities of daily living, and monitoring potential changes in hematological indicators. Our intervention will encompass a structured exercise rehabilitation program beginning at an appropriate phase of treatment and continuing through a defined follow-up period. This case study aims to provide preliminary evidence to guide the development of comprehensive rehabilitation protocols specifically designed for the FA population, addressing both the skeletal abnormalities and the systemic manifestations of the condition. More |
NCT00494442 :
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer
(Completed) Locations: Los Angeles, United States, San Francisco, United States, Boston, United States, New York, United States, Houston, United States, Melbourne, Australia, Melbourne, Parkville, Australia, Randwick, Australia, Cologne, Germany, Hospitalet deLlobregat, Spain, Lund, Sweden Los Angeles, United States, San Francisco, United States, Boston, United States, New York, United States, Houston, United States, Melbourne, Australia, Melbourne, Parkville, Australia, Randwick, Australia, Cologne, Germany, Hospitalet deLlobregat, Spain, Lund, Sweden Study Dates: Start: June 11, 2007 | Actual Completion Date: July 20, 2017 Study Overview: No description available. No description available. |
NCT00305708 :
Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
(Completed) Locations: San Francisco, United States San Francisco, United States Study Dates: Start: August 1, 2000 | Actual Completion Date: July 1, 2004 Study Overview: OBJECTIVES: OBJECTIVES: Primary * Determine the efficacy, in terms of graft rejection at 4 weeks, of a conditioning regimen comprising busulfan, anti-thymocyte globulin, and fludarabine followed by donor stem cell transplantation (SCT) in children with stem cell defects, marrow failure syndromes, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
* Determine the pharmacokinetics of busulfan in children undergoing donor SCT. Secondary * Determine the toxicity of this regimen in these patients.
* Determine engraftment at 3, 6, 9, and 12 months and mixed chimerism in patients treated with this regimen.
* Determine overall and disease-free survival of patients treated with this regimen. OUTLINE: Patients receive one of the following cytoreductive regimens: * Regimen 1 (patients with an HLA genotypic matched sibling donor): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, fludarabine IV on days -5 to -2, and anti-thymocyte globulin (ATG) IV over 10 hours on days -3 to -1.
* Regimen 2 (patients with an HLA closely matched related \[not genotypic\] or unrelated donor): Patients receive busulfan and fludarabine as in regimen 1, and ATG IV over 10 hours on days -4 to -1.
* Regimen 3 (patients with Fanconi's anemia or severe aplastic anemia with genotypic matched sibling donor): Patients receive fludarabine as in regimen 1 and ATG as in regimen 2.
* Regimen 4 (patients with Fanconi's anemia who have a closely matched related \[not genotypic\] or unrelated donor): Patients undergo thoracoabdominal irradiation on day -6 and receive fludarabine as in regimen 1 and ATG as in regimen 2. All patients undergo allogeneic bone marrow, umbilical cord blood, or peripheral blood stem cell transplantation on day 0. After the completion of study treatment, patients are followed periodically for 20 years. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study. More |
NCT00317876 :
Cyclophosphamide in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Fanconi's Anemia
(Completed) Locations: Seattle, United States, Seattle, United States, Curitiba, Brazil Seattle, United States, Seattle, United States, Curitiba, Brazil Study Dates: Start: June 1, 1998 Study Overview: OBJECTIVES: OBJECTIVES: * Decrease the conditioning-related toxicity of cyclophosphamide without decreasing the engraftment rate to \< 90% in patients undergoing allogeneic bone marrow transplantation for Fanconi's anemia. OUTLINE: This is a multicenter, dose-finding study of cyclophosphamide. * Nonmyeloablative conditioning regimen: Patients receive cyclophosphamide IV on days -5 to -2. Cohorts of 5-10 patients receive decreasing doses of cyclophosphamide until the optimal dose (OD) is determined. The OD is defined as the dose at which ≥ 4 of 5 patients achieve engraftment and \< 1 of 10 patients experiences dose-limiting toxicity. * Allogeneic bone marrow transplantation (BMT): Patients undergo allogeneic BMT on day 0.
* Graft-vs-host-disease (GVHD) prophylaxis: Patients receive cyclosporine orally or IV twice daily beginning on day -1 and continuing until day 49, followed by a taper on days 50-180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study. More |
NCT00413491 :
National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
(UNKNOWN) Locations: Copenhagen, Denmark, Esbjerg, Denmark, Hjørring, Denmark, Svendborg, Denmark Copenhagen, Denmark, Esbjerg, Denmark, Hjørring, Denmark, Svendborg, Denmark Study Dates: Start: January 1, 2007 Study Overview: Study type : Interventional Study design: Diagnostic,Prospective,Non Randomised,Blinded,Efficacy study Study type : Interventional Study design: Diagnostic,Prospective,Non Randomised,Blinded,Efficacy study Further study details as provided by DBCG ( Danish Breast Cancer Cooperative Group): Primary outcome measures: Diagnostic outcome of a yearly screening with MR versus combined mammography and ultrasound of the breast measured by accuracy, sensitivity, specificity, positive and negative predictive values. Secondary outcome measures: Comparison of diagnostic outcome of MR versus combined mammography and ultrasound, in women with dense breast tissue compared with women with fatty breast tissue. Comparison of the cancers found in women with BRCA gene mutations compared with the cancers found in the background population in respect of morphology, size, histological type, axillary lymph node status and grade. Study start : January 2007. Expected completion 2010. Women with BRCA gene mutations are more likely than others to develop the disease at a young age when breast density is higher than at older age.The tumours often are more rapidly developing with a short presymptomatic phase. These factors are known to reduce the effectiveness of screening with mammography and mammography seems to have a low sensitivity in women with BRCA gene mutations. Other studies have shown that more than 50% of the cancers appears as interval cancers between two mammography screening examinations and many have positive axillary nodes at the time of diagnosis. Around 610 women are tested BRCA gene positive in Denmark in year 2006. These women are offered a yearly screening with mammography combined with ultrasound and a clinical examination. The trial will test whether this screening offer should be combined with or replaced by MR mammography. More |
NCT01331018 :
Gene Therapy for Fanconi Anemia
(Terminated) Locations: Seattle, United States Seattle, United States Study Dates: Start: February 22, 2012 Study Overview: OUTLINE: OUTLINE: STEM CELL MOBILIZATION FOR CELL COLLECTION: Patients receive filgrastim subcutaneously (SC) twice daily (BID) for up to 6 days (on days 1-6 of mobilization). Patients receive plerixafor SC once daily (QD) on days 4-6 of mobilization. Peripheral blood stem cell (PBSC) count will be checked daily starting on day 4 of mobilization. Patients who have a PBSC count of \>= 5 CD34+ cells/mcL will undergo up to 2 apheresis collections on consecutive days. BONE MARROW HARVEST FOR CELL COLLECTION: Patients with inadequate PBSC counts undergo bone marrow harvest for collection of stem/progenitor cells. REINFUSION: Patients receive methylprednisolone intravenously (IV) or prednisone orally (PO) on days -1 to 7 followed by a rapid taper over approximately 1 week and undergo reinfusion of genetically modified hematopoietic stem/progenitor cells on day 0. After completion of study treatment, patients are followed up periodically for 15 years. More |
NCT06648096 :
Afatinib in Patients with Fanconi Anemia (FA) and Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
(Recruiting) Locations: Hanover, Germany, Barcelona, Spain Hanover, Germany, Barcelona, Spain Study Dates: Start: November 8, 2024 | Estimated Completion Date: December 1, 2028 Study Overview: No description available. No description available. |
NCT03814408 :
A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype A
(UNKNOWN) Locations: Stanford, United States Stanford, United States Study Dates: Start: January 11, 2019 Study Overview: This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+... This is a pediatric open-label Phase 1 clinical trial and will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. CD34+ cells will be transduced ex vivo with the therapeutic lentiviral vector and infused following transduction, without any prior conditioning. After transduction, product quality control evaluations will be carried out in aliquots of the transduced population. Investigational product will be infused via intravenous infusion with no upper or lower limit; a dose of ≥5 x 105 CD34+ cells/kg body weight will be considered optimal. The active agent is a self-inactivating lentiviral vector carrying the therapeutic FANCA gene and the therapeutic product is subject's autologous HSCs that have been transduced with the lentiviral vector. The vector contains the functional FANCA gene. More |
NCT00965666 :
Pilot Study of Etanercept (Enbrel) in Children With Fanconi Anemia
(Completed) Locations: Cincinnati, United States Cincinnati, United States Study Dates: Start: October 1, 2005 | Actual Completion Date: October 1, 2010 Study Overview: Patients with FA are treated with blood products (transfusions), injections to stimulate white blood cell production, and/or androgen therapy once they reach advanced stages of bone marrow failure.... Patients with FA are treated with blood products (transfusions), injections to stimulate white blood cell production, and/or androgen therapy once they reach advanced stages of bone marrow failure. Although these therapies lead to temporary improvement in the blood counts, they are associated with potential serious side effects. Currently, the only known potential cure for bone marrow failure in Fanconi Anemia is a stem cell transplant, which is usually done at the late stages of bone marrow failure and is again associated with significant toxicity. Studies show that patients with FA are very sensitive to and produce unusually high levels of a protein called tumor necrosis factor alpha (TNF-α) that causes bone marrow cells to die. We will study whether a drug called Etanercept that reduces levels of TNF-α will delay or prevent the progressive bone marrow failure associated with FA. Etanercept has been successfully used in children with arthritis. Primary Objectives: 1. To assess toxicity of Etanercept (Enbrel) in children with Fanconi Anemia (FA) and early marrow failure.
2. To assess efficacy of Etanercept (Enbrel) in improving hematopoiesis (i.e. peripheral counts) in patients with FA. Secondary Objectives: 1\) Correlation of biological studies to measure the impact of Etanercept (Enbrel) on Tumor Necrosis Factor - α (TNF-α) production. Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy, particularly acute myeloid leukemia (AML) 1. Cells from FA patients exhibit hypersensitivity to alkylating agents such as mitomycin C and diepoxybutane (DEB). Currently, FA is diagnosed by testing for chromosome breakage after lymphocyte stimulation and exposure to mitomycin C (MMC) or diepoxybutane (DEB) 2. Chromosome fragility, defined by an increased percentage of chromosome breaks, is diagnostic for FA3. Although it is the most common form of constitutional aplastic anemia it is very uncommon and the true incidence of FA is not known. A total of 754 patients from North America with the DEB confirmed diagnoses of FA were registered into the International Fanconi Anemia registry (IFAR) by 2001. The major cause of morbidity and mortality for children with FA is bone marrow failure that occurs in the majority of children in the first and second decades of life. Attempts to culture bone marrow progenitors in vitro from FA patients demonstrate decreased numbers of myeloid and erythroid colonies, which is consistent with clinical bone marrow failure. Current treatment for FA relies upon hematological support in the form of transfusions once advanced marrow failure occurs. Patients with FA do not respond to anti-thymocyte globulin or cyclosporine (typical treatments for acquired aplastic anemia), but 50% improve with androgen preparations, with a median prolongation of life of 2 years in responders (from 16 years to 18 years of age at death) although relapses are inevitable. Androgen therapy causes significant liver toxicity, virilization and risk of hepatic adenoma or carcinoma. Patients who do not respond to these modalities are treated with stem cell transplantation, with its associated toxicities from the transplant conditioning regimens, graft-versus-host disease and increased risk of post transplant malignancy compared to patients without FA. Five-year survival after a matched sibling transplant is approximately 65%. After an unrelated donor transplant, five-year survival is about 30%. The natural history of this disease is one of eventual death by age 10 to 20 years from progressive marrow failure or from conversion to AML (in approximately 10% of patients). Thus there is clearly a need for an effective and early therapy with better toxicity profile. Studies in both animals and human subjects indicate that high levels of systemic TNF-α and increased sensitivity of hematopoietic progenitors to TNF-α plays a key role in pathogenesis of bone marrow failure in patients with FA. This suggests a possible benefit in supporting hematopoiesis with anti-TNF-α receptor Fc fusion protein (Etanercept; Enbrel) in children with FA. This study proposes to treat patients with FA and early marrow failure with Etanercept (Enbrel), a medication used to treat rheumatoid arthritis. The results of the proposed project will use important preclinical data (see below) to support the development of a novel therapeutic approach for treatment of marrow failure in FA. Etanercept (Enbrel) will prevent the progressive marrow failure and associated complications without the need for transplant and if found to be effective, this treatment can be included in standard clinical care of FA patients, potentially for many years. More |
NCT01327807 :
Cure Cystinosis International Registry
(UNKNOWN) Locations: San Diego, United States San Diego, United States Study Dates: Start: August 1, 2010 Study Overview: Significance and Purpose: Significance and Purpose: Many different resources and tools are necessary to make significant advances in medical research. Progress in rare diseases such as cystinosis can often be impeded by the lack of information available about the disease and limited access to volunteers eligible for clinical trials. Therefore, patients who are willing to provide information about how the disease has affected them and also make themselves available to participate in trials are among the most valuable resources the investigators have to fight a disease. However, the research community desperately needs the right tool that will permit access to these resources. A tool widely used to conveniently collect both data about a disease and information about potential clinical trial participants is a patient registry. A patient registry is any system that allows for the organized collection of data about disease outcomes in affected populations for a scientific, clinical, or policy purpose. The Cystinosis Research Foundation (CRF) has aligned itself with cystinosis medical experts and organizations worldwide to create the first ever international, online patient registry for cystinosis, Cure Cystinosis International Registry (CCIR). The express purpose of CCIR is to make anonymous information available to the research community and thus promote accelerated research in advanced treatments and ultimately a cure for cystinosis. Objectives: The objectives of CCIR are: * Evaluate epidemiology and clinical characteristics of cystinosis around the world.
* Evaluate and compare the diagnosis, treatment, and kidney transplant rates among cystinosis communities from different geographical areas.
* Enhance the understanding of how cystinosis affects quality of life. CCIR Registration: Interested cystinosis patients may register themselves with CCIR online at http://www.cystinosisregistry.org. Registration is easy and secure. Simply go to the website and create a CCIR account and complete a survey. The CCIR website is currently available in English and Spanish, and will soon be available in French, Portuguese, and possibly other languages. Benefits to CCIR participants include instant access to the registry's accumulated survey results (reported as anonymous group data), and opportunities to submit questions to cystinosis experts and to learn of clinical trial opportunities. No personal information is shared outside of CCIR. Individual identities are known only to appropriate CCIR staff. More |
NCT03157804 :
Lentiviral-mediated Gene Therapy of Fanconi Anemia Patients Subtype A
(Completed) Locations: Barcelona, Spain, Madrid, Spain Barcelona, Spain, Madrid, Spain Study Dates: Start: January 7, 2016 | Actual Completion Date: September 8, 2023 Study Overview: The main objective of this open-label Phase I / II clinical trial is to evaluate the safety and therapeutic efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a... The main objective of this open-label Phase I / II clinical trial is to evaluate the safety and therapeutic efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi's Anemia Subtype A. The drug to be administered to the patients consists of the cellular product resulting from the transduction of autologous CD34 + cells with the therapeutic lentiviral vector PGK-FANCA.Wpre \*. The dose of cells to infuse in the patients will be that obtained from the transduction process of between 3x10\^5 and 4x10\^6 CD34 + cells / kg of patient body weight. The cells will be infused intravenously in a single dose, after complete the transduction process. Follow-up period: 3 years after infusion of transduced cells. However, patients will be monitored outside the clinical trial over a 10-year period. Follow-up of the grafted transduced cells will be performed on peripheral blood and bone marrow samples. More |
NCT04232085 :
Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
(Recruiting) Locations: Baltimore, United States Baltimore, United States Study Dates: Start: February 12, 2020 | Estimated Completion Date: December 31, 2028 Study Overview: Allogeneic blood and marrow transplantation (alloBMT) is the only curative therapy for many primary immune deficiencies (PID), immune dysregulatory syndromes (IDS), and inherited bone marrow failure... Allogeneic blood and marrow transplantation (alloBMT) is the only curative therapy for many primary immune deficiencies (PID), immune dysregulatory syndromes (IDS), and inherited bone marrow failure syndromes (IBMFS). The best reported outcomes are with human leukocyte antigen (HLA)- matched sibling donors, however, only 30% of children in need of a BMT have an HLA-matched sibling. Use of alternative donors has been limited by unacceptably high rates of transplant-related mortality (TRM), graft rejection, infection, and graft-versus-host disease (GVHD). Reduced intensity conditioning (RIC) regimens have been used for this patient population with improved survival and decreased TRM, but graft failure and sustained donor chimerism have emerged as significant obstacles. Thus, there is an urgent need to develop a RIC platform that improves survival and decreases TRM while maximizing donor engraftment, which is essential for cure. A large and growing body of literature demonstrates that post-transplant cyclophosphamide (PTCy) allows for the safe and effective use of HLA-matched and mismatched related and unrelated donors and haploidentical related donors after RIC alloBMT. PTCy offers a unique opportunity to 1) broaden donor availability, 2) promote durable engraftment of donor cells, 3) achieve low rates of GVHD and TRM, 4) foster robust immune reconstitution and immunity, and 5) shorten the duration of additional post-transplant immune suppression (IS) required to prevent GVHD. The investigators proposed platform is uniquely suited for success in this context, to broaden the scope of RIC alloBMT with PTCy as a curative therapy for patients with PID/IDS and IBMFS. This is a Phase II single arm trial to prospectively study a RIC BMT with PTCy to enhance durable engraftment of donor cells and improve outcomes for patients with PID/IDS and IBMFS. Treatment Plan: Indwelling central venous catheter Placement of a double lumen central venous catheter will be required for administration of IV medications and transfusion of blood products. Pre-treatment Evaluation All patients will require documentation of a detailed history and physical examination and standard evaluation of cardiac, pulmonary, liver and renal function. All patients will undergo disease evaluation. Pre-BMT blood will be drawn for correlative labs. Preparative regimen Alemtuzumab: administered as an IV infusion on days -14 to -12. For patients \>10 kg, 3 mg IV test dose over 2 hours followed by 10 mg IV over 2 hours on day -14, 15 mg IV over 2 hours on day -13, and 20 mg IV over 2 hours on day -12. For patients \<10 kg, doses are 3 mg, 10 mg, 10 mg, and 10 mg. Fludarabine: administered as an IV infusion over 30 minutes on days -7 to -3. The dose will be 30 mg/m2/dose (adjusted for renal function). Melphalan: Recommended to be administered as an IV infusion over 30-60 minutes, depending on volume, on days -3 and -2. The dose will be 70 mg/m2/dose. Alternatively, may be given as 140 mg/m2/dose as a single dose IV infusion per institutional standards on day -2. Other institutional infusion standards are acceptable and will not be a protocol deviation. Total body irradiation: 200 centigray (cGy) anterior-posterior-posterio-anterior (AP/PA) with 4 megavolt (MV) or 6 MV photons at 8 12 cGy/min at the point of prescription (average separation of measurements at mediastinum, abdomen, and hips) will be administered in a single fraction on day -1. This is only for patients with PID/IDS. Bone marrow transplantation Bone Marrow will be harvested and infused on day 0. Institutional guidelines for the infusion of bone marrow (i.e. major or minor blood type group (ABO) incompatible bone marrow, etc.) will be followed. The marrow infusion will be done by designated members of the BMT team. The bone marrow graft will not be manipulated to deplete T cells. The donor will be harvested with a target yield of 4 x 10\^8 nucleated cells/kg recipient ideal body weight (IBW). The lowest acceptable yield is 2 x 10\^8 nucleated cells/kg. The cluster of differentiation (CD)-34+, CD4+, CD8+, and CD3+ cell count in the marrow will be quantified by flow cytometry. Bone marrow graft should be hung to gravity (not infused with a pump). If possible, the total infusion time should be no more than four hours. GVHD prophylaxis Post-transplantation Cyclophosphamide (PTCy) Cyclophosphamide (Cy) 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Cyclophosphamide will be given as an IV infusion over 1- 2 hours (depending on volume). Dosing of cyclophosphamide is based on ideal body weight for subjects whose ideal body weights less than or equal to subjects' actual body weight. On occasion, a subject's actual body weight may be less than his/her ideal body weight, in which case cyclophosphamide will be dosed using the subject's actual body weight. Patients will be instructed to increase fluids overnight before cyclophosphamide administration. Hydration with normal saline at 3 cc/kg/hr iv will be started 8 hr prior to cyclophosphamide, then the rate will be reduced to 2 cc/kg/hr for 1 hr pre-cyclophosphamide and continued for at least 8 hr post-cyclophosphamide or administered per institutional standards. Mesna will be given IV at 10 mg/kg/dose concurrent with cyclophosphamide infusion, followed by 40 mg/kg/dose IV over 24 hours, or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of mesna is equal to 100% of the total daily dose of cyclophosphamide. It is crucial that no immunosuppressive agents are given until 24 hours after the completion of the post-transplant Cyclophosphamide. This includes steroids as anti-emetics. Steroids for disease treatment will attempt to be weaned but are allowed if wean is not possible. Physiologic and stress dose steroids are allowed if necessary. Steroids are allowed as pre-medications if needed. Tacrolimus On day +5, patients will begin prophylaxis with Tacrolimus (oral (PO) or intravenous (IV) as per institutional standards for starting this prophylaxis).Tacrolimus begins on Day 5, at least 24 hours after completion of post-transplantation Cy. The tacrolimus starting dose will be given per institutional standards for adult or pediatric patients. The recommended, but not required, The starting dose of tacrolimus is 0.015mg/kg IBW/dose IV over 4 hours every 12 hours. , or per institutional standard. Serum trough levels of tacrolimus should be measured around D+7 and the dose should be adjusted based on this level to maintain a level of 5-15 ng/ml. Tacrolimus should be converted to oral dosing when patient has a stable, therapeutic level and is able to tolerate food or other oral medications. For pediatric patients, the oral dosing is approximately two to four times the IV dosing. It is recommended that serum trough levels should be checked at steady state after any dose modification and when switching from IV to oral to ensure therapeutic trough concentrations. Serum trough concentrations should be checked at a minimum weekly thereafter and the dose adjusted accordingly to maintain a level of 5-15 ng/ml. Tacrolimus will be discontinued after the last dose on Day 60 for matched related donors, Day 120 for matched unrelated donors, and day 180 for haploidentical related or mismatched unrelated donors; or may be continued if active GVHD is present. This should be discussed with the PI. Mycophenolic acid mofetil (MMF) MMF will be given at a dose of 15 mg/kg PO three times daily (TID) (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID). MMF prophylaxis will be discontinued after the last dose on day 35. Growth factor support Patients will receive Granulocyte-colony stimulating factor (GCSF) (Filgrastim®) 5µg/kg/d subcutaneous (SC) or IV starting at Day 5 and continuing until the absolute neutrophil count (ANC) \>1000/mm3 x 3 days. For use in the case of fungal infections or subsequent neutropenia (ANC \<500/mm3), GCSF should be continued at the discretion of the treating physician. Transfusion support Platelet and packed red cell transfusions will be given per current institutional recommendations. Infection prophylaxis and therapy All infection prophylaxis and therapy will be administered and discontinued as per institutional requirements. The following are recommendations only. i) During pre-transplant evaluation patients will be screened for respiratory syncytial virus (RSV) and influenza A and B, as well as parainfluenza and other respiratory viruses if symptomatic. Assays of these viruses must be negative for patients to be admitted for transplant. Consideration should be given to institution of antiviral therapy if positive prior to transplant. ii) Oral hygiene will be maintained according to institutional standards. iii) Antifungal prophylaxis will be administered according to institutional practices. It is important to follow levels of tacrolimus for patients receiving one of the azole antifungal medications. The combination of both drugs can raise the levels of the immunosuppressant to toxic levels. If a patient on tacrolimus is started on an azole antifungal medication, a dose reduction of the tacrolimus is required and levels should be obtained to ensure patients are not in the toxic range. iv) Pneumocystis jiroveci pneumonia (PJP) prophylaxis will be administered according to institutional practices. Recommendations include administering during the preparative regimen, and then restarting approximately one month post-BMT (or later if white blood cell count (WBC) not recovering) and continuation until at least one year post-BMT. v) Viral prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) will be administered according to institutional practices. Recommendations include continuation for at least one year post-BMT and/or while on immunosuppressive medications. vi) Prophylactic and empiric antibiotics as well as intravenous immunoglobulin (IVIg) will be administered according to institutional practices. vii) Re-immunization may be performed according to institutional practices. Anti-ovulatory treatment Menstruating females will are recommended to should be be started on an anti-ovulatory agent, such as Lupron prior to the initiation of the preparative regimen. The treatment administered will be at the discretion of the treating physician. Post-BMT evaluation Patients will be followed during (i) the initial post-BMT period (ii) after discharge to the referring physician as per standard practice. More |
NCT00438906 :
Cancer of the Pancreas Screening Study (CAPS 3)
(Completed) Locations: Baltimore, United States Baltimore, United States Study Dates: Start: December 1, 2006 | Actual Completion Date: December 1, 2009 Study Overview: Pancreatic cancer (PC) is the 4th leading cause of cancer death in the U.S. Because it is seldom diagnosed at an early curable stage, nearly all patients die from their disease. Early detection of PC... Pancreatic cancer (PC) is the 4th leading cause of cancer death in the U.S. Because it is seldom diagnosed at an early curable stage, nearly all patients die from their disease. Early detection of PC and its precursors will save lives. In a multi-center, translational prospective controlled cohort study, we propose to screen high-risk individuals (members of familial pancreatic cancer kindreds and/or those with germline mutations of BRCA-2, p16, or STK-11), using EUS, CT, and MRI and test a panel of candidate biomarkers. Patients with suspected neoplasms will be offered surgery and the resected pancreata will be examined by an expert pathologist. Pathological results will be compared with radiologic findings and biomarker results. Our study hypothesis is that screening tests can detect early curable non-invasive pancreatic neoplasia in high risk individuals before it progresses to invasive cancer. The primary specific aim of this study is to determine the frequency of detectable pancreatic neoplasia in individuals with an inherited predisposition for pancreatic cancer. Our additional specific aims are: 1) To test the value of a newly-developed method (PANCPRO) of calculating the risk families have of developing PC so as to best target who might benefit from screening; 2a). To compare performance characteristics and reliability of the pancreatic imaging tests EUS, CT, and MRI/MRCP for the detection of early pancreatic neoplasia; 2b) To determine the prevalence of abdominal and pelvic tumors by CT and MRI in individuals carrying a germ-line BRCA2 gene mutation and patients with Peutz-Jeghers syndrome; 2c) To correlate radiologic abnormalities with histologic findings in resected pancreata; and 3). To validate a panel of candidate DNA and protein markers (CA19-9, macrophage inhibitory cytokine-1 (MIC-1), DNA hypermethylation, and KRAS gene mutations) in pancreatic juice and serum as indicators of prevalent neoplasms in high risk individuals, compared to concurrently enrolled controls. |
NCT02503436 :
C-PATROL - Non-interventional Study (NIS) to Collect Clinical and Patient Reported Outcome Data in an Olaparib Treated BRCAm+ PSR Ovarian Cancer Population
(Completed) Locations: Amberg, Germany, Aschaffenburg, Germany, Augsburg, Germany, Bad Homburg, Germany, Berlin, Germany, Bonn, Germany, Bottrop, Germany, Brandenburg... Amberg, Germany, Aschaffenburg, Germany, Augsburg, Germany, Bad Homburg, Germany, Berlin, Germany, Bonn, Germany, Bottrop, Germany, Brandenburg, Germany, Braunschweig, Germany, Bremen, Germany, Chemnitz, Germany, Coburg, Germany, Cologne, Germany, Donauwörth, Germany, Dortmund, Germany, Dresden, Germany, Duisburg, Germany, Düsseldorf, Germany, Erlangen, Germany, Essen, Germany, Esslingen am Neckar, Germany, Eutin, Germany, Frankfurt, Germany, Freiburg im Breisgau, Germany, Fürstenwalde, Germany, Georgsmarienhütte, Germany, Halle, Germany, Hamburg, Germany, Hanover, Germany, Heidelberg, Germany, Heidenheim, Germany, Hildesheim, Germany, Homburg/Saar, Germany, Jena, Germany, Karlsruhe, Germany, Kassel, Germany, Kempten, Germany, Kiel, Germany, Krefeld, Germany, Kulmbach, Germany, Landshut, Germany, Lübeck, Germany, Mainz, Germany, Mannheim, Germany, Mönchengladbach, Germany, Mutlangen, Germany, München, Germany, Münster, Germany, Nuremberg, Germany, Oberhausen, Germany, Osnabrück, Germany, Paderborn, Germany, Plauen, Germany, Regensburg, Germany, Rosenheim, Germany, Rostock, Germany, Saarbrücken, Germany, Schwerin, Germany, Singen, Germany, Solingen, Germany, Stralsund, Germany, Stuttgart, Germany, Traunstein, Germany, Troisdorf, Germany, Tübingen, Germany, Wiesbaden, Germany, Wolfsburg, Germany, Würzburg, Germany More Study Dates: Start: October 28, 2015 | Actual Completion Date: December 1, 2022 Study Overview: No description available. No description available. |
NCT02873975 :
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency
(Completed) Locations: Boston, United States Boston, United States Study Dates: Start: October 12, 2016 | Actual Completion Date: July 1, 2021 Study Overview: This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following: This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following: 1. Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation
2. An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes
3. A CCNE1 amplification More |
NCT06910813 :
DFT383 in Pediatric Participants With Nephropathic Cystinosis
(Recruiting) Locations: San Diego, United States, Stanford, United States, Atlanta, United States San Diego, United States, Stanford, United States, Atlanta, United States Study Dates: Start: June 2, 2025 | Estimated Completion Date: August 26, 2030 Study Overview: This study is an open-label, multi-center, phase I/II study to assess the safety, tolerability, and efficacy of DFT383 in participants aged 2 to 5 years with nephropathic cystinosis. The study... This study is an open-label, multi-center, phase I/II study to assess the safety, tolerability, and efficacy of DFT383 in participants aged 2 to 5 years with nephropathic cystinosis. The study consists of participants receiving DFT383 in Cohort 1 and Standard of Care (SoC) in Cohort 0. The two cohorts will be run in parallel. Investigational sites may participate in one or both cohorts. Cohort 1 Approximately 15 participants will receive treatment with DFT383 in 3 cohorts (1A, 1B and 1C) dosed in a staggered approach. The total study duration for a participant in Cohort 1 will be up to 32 months. Cohort 0 Approximately 15 participants meeting similar inclusion/exclusion criteria and receiving SoC will be enrolled. The Schedule of Activities will be reduced for this Cohort. This cohort 0 is not a direct control but will provide essential context for interpreting the results observed in the participants receiving DFT383. The total study duration for a participant in Cohort 0 will be up to 24 months. More |
NCT02143830 :
HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
(Recruiting) Locations: New York, United States, Cincinnati, United States, Seattle, United States New York, United States, Cincinnati, United States, Seattle, United States Study Dates: Start: April 1, 2014 | Estimated Completion Date: July 1, 2027 Study Overview: The trial proposed is a three arm phase II treatment protocol designed to investigate the safety and efficacy of risk-adjusted chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell... The trial proposed is a three arm phase II treatment protocol designed to investigate the safety and efficacy of risk-adjusted chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Candidates for this trial will include patients with Fanconi anemia presenting with severe marrow failure (transfusion dependent) or myelodysplastic syndrome, or acute myelogenous leukemia for whom an allogeneic stem cell transplant is indicated. |
NCT00053989 :
NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
(Completed) Locations: Buffalo, United States Buffalo, United States Study Dates: Start: January 29, 2002 | Actual Completion Date: July 19, 2018 Study Overview: OBJECTIVES: OBJECTIVES: * Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
* Determine clinical response and overall outcome of patients treated with this regimen.
* Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen. OUTLINE: * Preparative regimen: * Matched related and unrelated donor transplantation: * Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
* Cord blood transplantation: * Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.
* Graft-vs-host disease (GVHD) prophylaxis: * Matched related and unrelated donor transplantation: * Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering\* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.
* Cord blood transplantation: * Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.
* Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
* Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI. Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years. PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years. More |
NCT00093743 :
Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
(Completed) Locations: Chicago, United States, Indianapolis, United States, Nashville, United States, Salt Lake City, United States, Seattle, United States Chicago, United States, Indianapolis, United States, Nashville, United States, Salt Lake City, United States, Seattle, United States Study Dates: Start: January 1, 2000 Study Overview: PRIMARY OBJECTIVES: PRIMARY OBJECTIVES: I. To determine whether donor chimerism can be achieved in patients with Fanconi anemia receiving marrow or peripheral blood stem cell (PBSC) grafts from unrelated donors following low dose total body irradiation (TBI), fludarabine (fludarabine phosphate), mycophenolate mofetil, and cyclosporine. II. To determine the lowest dose of TBI necessary to achieve donor chimerism in at least 80% of patients. III. To determine the incidence of severe regimen-related toxicity. SECONDARY OBJECTIVES: I. To determine the survival of Fanconi anemia patients transplanted with unrelated donor marrow or PBSC grafts after conditioning with a non-myeloablative regimen. II. To determine the incidence and severity of graft-vs-host disease (GVHD) incurred with unrelated bone marrow or PBSC grafts transplant patients with Fanconi anemia. III. To determine if mixed chimerism results in amelioration of symptoms associated with bone marrow failure in patients with Fanconi anemia. OUTLINE: NON-MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2, cyclosporine IV every 8-12 hours on days -3 to 0, and undergo low-dose TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic bone marrow or PBSC transplantation on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) or IV every 8-12 hours on days 1-100 with taper to day 177, and mycophenolate mofetil PO or IV every 8 hours on days 0-40 with taper to day 96. After completion of study treatment, patients are followed up at 6 months and annually thereafter. More |
NCT00590460 :
Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
(Terminated) Locations: Houston, United States, Houston, United States Houston, United States, Houston, United States Study Dates: Start: July 1, 2001 Study Overview: If clinically feasible (no aplasia, no active malignancy), the recipients marrow will be harvested and cryopreserved as a back up for use if non-engraftment/rejection is followed by failure to... If clinically feasible (no aplasia, no active malignancy), the recipients marrow will be harvested and cryopreserved as a back up for use if non-engraftment/rejection is followed by failure to undergo autologous reconstitution. For HLA Mismatched donors, harvested peripheral blood stem cells will be enriched for CD34 cells using the Clinimacs CD34 Reagent system. Fludarabine will be given as 5 daily intravenous infusions. Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered intravenously every 4 hours during the period of the course of each infusion. Day -8 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -7 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -6 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -5 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2 -4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2 -3 YTH 24/54 400ug/kg over 6 hr -2 YTH 24/54 400ug/kg over 6 hr -1 -0 Stem Cell Infusion GVHD prophylaxis will be achieved through positive selection for CD34 resulting in \> 3 log T cell depletion. Previous reports have indicated that there is a low frequency of severe (Grade II/IV) GvHD after haploidentical transplants if recipients receive stem cell populations containing \<5 x 10e4 CD3 positive T cells. We hope to achieve such levels with our CD34 enrichment protocol. However, pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10e4 CD3+ve T cells/kg recipient weight. In addition, Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity, in vivo. More |
NCT04954599 :
Phase 1/2 Clinical Trial of CP-506 (HAP) in Monotherapy or With Carboplatin or ICI
(Recruiting) Locations: Brussels, Belgium, Ghent, Belgium, Maastricht, Netherlands, Rotterdam, Netherlands, Barcelona, Spain Brussels, Belgium, Ghent, Belgium, Maastricht, Netherlands, Rotterdam, Netherlands, Barcelona, Spain Study Dates: Start: May 30, 2023 | Estimated Completion Date: May 1, 2027 Study Overview: This study is a First in Human, early phase (I/IIa), 3 modules, 2 parts (A- dose escalation and B- cohort expansion), open-label, uncontrolled, multi-center, multiple dose, accelerated 3+3 dose... This study is a First in Human, early phase (I/IIa), 3 modules, 2 parts (A- dose escalation and B- cohort expansion), open-label, uncontrolled, multi-center, multiple dose, accelerated 3+3 dose escalation study. The study consist of 3 study modules. Module 1 is monotherapy with accelerated dose escalation. Modules 2 and 3 are also accelerated dose escalation modules, but with a combination of CP-506 with either Carboplatin or ICI. Initiation of modules 2 and 3 are dependent on the decision by the Independent Data Monitoring Committee (IDMC) based on the safety, tolerability and feasibility information from the study as a whole. Each study modules will consist of a Part A (dose finding) and an optional Part B (cohort expansion). The option to start Part B will be decided by the IDMC based on safety, tolerability and feasibility information from the study as a whole. The expansion cohorts will explore preliminary efficacy. Modules 2 and 3 will start after completion of module 1 and definition of the "minimal biological effective dose" (MBED) as the dose that results in 1) a decrease of 20% of hypoxia radiomics score on sequential CT of at least one lesion OR 2) a decrease of 20% of the initial tumour volume of at least one lesion. MBED is assessed by CT scan at visit 7, 12 and 13. After observation of an MBED in three patients, the data supporting the MBED assessment will be reviewed by the IDMC for confirmation. A maximum of 126 patients with advanced or metastatic cancer will be recruited in this study. * Module 1 - Monotherapy: up to 24 patients for Part A and 10 patients for Part B for whom no standard of care or known effective treatment options are available and with cancers that show a considerable incidence of Homologous Recombination or Fanconi Anaemia DNA repair defects (HRD/FAD)
* Module 2 - Combination with Carboplatin: up to 24 patients for Part A and 22 patients for Part B for patients that receive carboplatin as standard of care: triple negative breast cancer and ovarian cancer.
* Module 3 - Combination with ICI: up to 24 patients for Part A and 22 patients for Part B with advanced or metastatic cancer for whom standard of care immune checkpoint inhibitor (ICI) are currently administered for at least 6 months, would still be administered according to the treating clinician, outside any clinical trial but resulted in oligoprogression. The complete CP-506 therapy consists of three cycles of CP-506 treatment. Each treatment cycle consists of three consecutive days of IV infusion for two hours and one day for observation and blood sampling, and a recovery time of 3 weeks. Patients are expected to come to the hospital for 18 visits. They consist of 1 screening visit, 3 cycles of CP-506 treatment. Each cycle will be followed by a post cycle visit after 14 and 21 days. The follow up visit will take place at day 105. More |
NCT04425200 :
Prevalence of HRR-related Genes Mutations and Prognosis in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients in Real World Setting
(Completed) Locations: Nagoya, Japan, Nagoya, Japan, Hirosaki, Japan, Kashiwa, Japan, Tōon, Japan, Kure, Japan, Hakodate, Japan, Sapporo, Japan, Sapporo, Japan, Kobe... Nagoya, Japan, Nagoya, Japan, Hirosaki, Japan, Kashiwa, Japan, Tōon, Japan, Kure, Japan, Hakodate, Japan, Sapporo, Japan, Sapporo, Japan, Kobe, Japan, Kobe, Japan, Tsukuba, Japan, Kanazawa, Japan, Hiragi, Japan, Yokohama, Japan, Yokohama, Japan, Kashihara, Japan, Sayama, Japan, Kawagoe, Japan, Yonago, Japan, Ube, Japan, Chiba, Japan, Gifu, Japan, Kyoto, Japan, Miyazaki, Japan, Okayama, Japan More Study Dates: Start: July 29, 2020 | Actual Completion Date: December 18, 2020 Study Overview: No description available. No description available. |
NCT04613440 :
FaCT Trial (Facilitated Cascade Testing Trial)
(Recruiting) Locations: New York, United States, Durham, United States, Houston, United States New York, United States, Durham, United States, Houston, United States Study Dates: Start: July 21, 2021 | Estimated Completion Date: December 1, 2026 Study Overview: This prospective randomized controlled trial will compare the efficacy of a multicomponent facilitated cascade testing intervention. One hundred and fifty probands with a diagnoses of a BRCA1/2... This prospective randomized controlled trial will compare the efficacy of a multicomponent facilitated cascade testing intervention. One hundred and fifty probands with a diagnoses of a BRCA1/2 mutation will be enrolled and randomized to the intervention vs. control arms. Probands will be asked to share the names and contact information for all FDR (First Degree Relative) with whom they have shared their genetic testing results. One hundred and fifty probands will be recruited and randomized and, therefore, based on our institutional experience, the investigators anticipate on average 3 FDRs per proband, therefore up to 450 FDRs. Probands randomized to the standard of care group will be instructed to share a family letter (providing information on the familial mutation) with their FDRs and encourage FDRs to complete genetic testing. In the intervention group, a patient navigator will provide facilitated support, including an initial genetic counseling call, an email with a link to an educational video, and, for individuals who are interested in completing testing - a link to create an account for a free genetic testing saliva kit and a follow-up call to discuss the results and ensure participants are connected with their primary care provider or other clinician, as appropriate. Participating FDRs will complete quality of life assessments. FDRs found to have BRCA1/2 mutations will be followed to determine if they completed cancer risk-reducing surveillance or surgery as a result of the genetic testing results. Analyses will assess the proportion of first degree relatives who complete genetic testing by 6 months (primary outcome), as well as the proportion who engage subsequently in recommended risk-reducing behaviors by 18 months and quality of life; distributions of time between proband diagnosis and first degree relative testing; and potential covariate correlations. Probands at WCM only who do not meet eligibility criteria for randomization to the intervention and control arms will be offered enrollment in a third arm, in which they will receive the intervention in addition to the option for referral to patient advocacy/support groups including FORCE: Facing Hereditary Cancer EMPOWERED, Sharsheret, SHARE, LatinaSHARE, Oneinforty, Susan G. Komen, Any Mountain, and Genetic Support Foundation, for additional guidance. Probands enrolled in this third arm only will be asked to share the names and contact information for all first, second, and third-degree relatives with whom they have shared their genetic testing results. We estimate enrolling up to 200 subjects into this exploratory third arm (50 probands and 150 Relatives including first, second, and third-degree relatives).The combined total enrollment for the randomized probands and FDRs, and the probands and relatives (first, second, and third-degree relatives) enrolled in the third arm will total 800. To recruit patients for all arms of this study, we will identify eligible probands from any of the following sources: Genetic Counselors, Institutional Clinicians, BRCA Genetics Conferences, and by reviewing clinic schedules on weekly basis for potentially eligible patients. |
NCT05903365 :
Observational Follow-up Study of Haplo-identical Transplants in Fanconi Disease
(Not Yet Recruiting) Locations: Not specified Not specified Study Dates: Start: June 1, 2023 | Estimated Completion Date: March 1, 2028 Study Overview: Fanconi's disease is characterised by a constitutional defect in DNA repair which results in the occurrence of bone marrow failure and haematological malignancies, mainly myeloid: at the age of 40,... Fanconi's disease is characterised by a constitutional defect in DNA repair which results in the occurrence of bone marrow failure and haematological malignancies, mainly myeloid: at the age of 40, the cumulative incidence of these two types of pathology reaches almost 100%. The only curative treatment for haemtalogocial diseases is allogenic hematopoietic stem cell transplant. Transplantation modalities must be adapted to the particular susceptibility of these patients to DNA bridging agents and radiotherapy. HSC transplantation is indicated with an unaffected matched related or matched unrelated donor when the patient has severe bone marrow failure or a poor prognostic clonal evolution (cytogenetic evolution or proven haemopathy). Alternative transplants (9/10 pheno-identical, haplo-identical and placental blood donors) were no longer proposed in most cases due to the frequency of severe complications (graft-versus-host disease, viral infections) and the catastrophic medium-term survival of around 40% (Dufort, Bone Marrow Transplant 2012, Gluckman Biol Blood Marrow Transplant. 2007). The development over the last decade of new haploidentical or phenoidentical 9/10 transplant protocols with unmodified grafts and GVH prophylaxis with post-transplant cyclosphosphamide or ex vivo T-depletion adapted to the particular susceptibility of patients with Fanconi disease has reduced the incidence of these severe complications. This observational protocol will allow for an independent, prospective evaluation of the improvement in survival of patients with Fanconi disease in hematological deadlock due to the absence of an HLA-identical donor and having received a haploidentical transplant More |
NCT02418624 :
Phase I of Carboplatin-Olaparib Followed by Olaparib Monotherapy in Advanced Cancer
(Completed) Locations: Amsterdam, Netherlands Amsterdam, Netherlands Study Dates: Start: May 1, 2015 | Actual Completion Date: January 1, 2019 Study Overview: A 3+3 dose escalation trial of 2 cycles (21 days) carboplatin and olaparib combination therapy, followed by olaparib monotherapy until progression or unacceptable toxicity in patients with advanced... A 3+3 dose escalation trial of 2 cycles (21 days) carboplatin and olaparib combination therapy, followed by olaparib monotherapy until progression or unacceptable toxicity in patients with advanced cancer. |
NCT00900055 :
Research Study in Healthy Volunteers of Patients With Fanconi Anemia, Myeloproliferative Disorders, or Myeloma
(Completed) Locations: Portland, United States Portland, United States Study Dates: Start: June 1, 1975 | Actual Completion Date: August 23, 2016 Study Overview: OBJECTIVES: OBJECTIVES: * Identify the specific molecular function of the Fanconi anemia (FA) complementing gene products in hematopoietic progenitor cells from patients and normal volunteers.
* Identify functional defects in hematopoietic stromal cells, including macrophages, from patients with FA, and selected blood cancers as well as normal volunteers. OUTLINE: Peripheral blood mononuclear leukocytes, skin fibroblasts, and marrow fibroblasts are collected for loss-of-function and gain-of-function analysis related to the Fanconi anemia complementing gene. More |
NCT00516373 :
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)
(Completed) Locations: Brussels, Belgium, Amsterdam, Netherlands, Szczecin, Poland, Edinburgh, United Kingdom, London, United Kingdom Brussels, Belgium, Amsterdam, Netherlands, Szczecin, Poland, Edinburgh, United Kingdom, London, United Kingdom Study Dates: Start: July 11, 2005 | Actual Completion Date: April 26, 2023 Study Overview: No description available. No description available. |
NCT06744283 :
Experience and Management of Cancer Screening-Related Anxiety in Fanconi Anemia
(Recruiting) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: October 13, 2025 | Estimated Completion Date: January 30, 2026 Study Overview: Study Description: Study Description: This study will explore the experience and management of screening related anxiety in Fanconi Anemia (FA) among participants in the Fanconi Anemia Cancer Screening Study (FACSS) protocol (NIH IRB #:001109). Knowledge generated from this study will improve understanding of the experience and management of cancer screening-related anxiety in the context of complex, rare disease, while providing much-needed information about the health experiences and challenges within the FA community. Objectives: To collect ethnographic observational field notes to explore the nature of cancer screening-related anxiety experienced by participants in the FACSS screening study at the NIH clinical center. More |
NCT00595127 :
Hematopoietic Stem Cell Transplantation for Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
(Completed) Locations: New York, United States New York, United States Study Dates: Start: June 1, 2001 | Actual Completion Date: May 1, 2013 Study Overview: Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for... Patients with this disease are born with it and have a fragility of the genes (chromosomes) in all the cells of the body. The fragility of the chromosomes puts patients with FA at high risk for certain cancers. Patients with FA are especially at risk of having diseases of the blood and marrow systems. These include (1) aplastic anemia, a disease where there is a failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is represented by a clone of cells of the marrow that becomes "malignant" and stops making adequate numbers of blood cells (it is also called preleukemia.) The progression of the myelodysplastic syndrome will lead to (3) acute leukemia. If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or leukemia standard treatment with medications or chemotherapy alone is not likely to cure these problems. An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to provide you with marrow or blood stem cells from a healthy donor that can develop a normal blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic stem cell transplants have been done for the treatment of FA using stem cells from donors other than matched siblings, they have been associated with a high risk of rejection of the transplant and of a complication called graft-versus-host disease. In order for the stem cells to grow and to kill leukemia cells, patients must receive chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients with Fanconi anemia, the standard preparation for stem cell transplantation has been the use of total body irradiation (at a lower dose because of the high risk of side-effects) and a chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has worked well with transplants from matched siblings, it was not enough in transplants from unrelated or cord blood donors and led to a high risk of rejection. In the last few years a medication called fludarabine was used successfully in transplants to give more immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low risks of rejection, and probably as importantly little risks of added side-effects. The addition of antithymocyte globulin to Total Body Irradiation, cyclophosphamide and fludarabine has made the chances of rejection very low. More |
NCT00005892 :
Study of Allogeneic Bone Marrow Transplantation Following Cyclophosphamide and Radiotherapy in Patients With Myelodysplastic Syndrome and Acute Leukemia Related to Fanconi's Anemia
(Completed) Locations: Minneapolis, United States Minneapolis, United States Study Dates: Start: March 1, 2000 Study Overview: PROTOCOL OUTLINE: PROTOCOL OUTLINE: Patients receive cyclophosphamide IV over 1-2 hours on day -6 through -3 and total body radiotherapy on day -1. Patients undergo allogeneic bone marrow transplantation on day 0. More |
NCT05687474 :
Baby Detect : Genomic Newborn Screening
(Completed) Locations: Liège, Belgium Liège, Belgium Study Dates: Start: September 1, 2022 | Actual Completion Date: June 2, 2025 Study Overview: Every year, thousands of children around the world are born with rare genetic diseases leading to death or lifelong disability. With technological advancements in the field of genetics and medicine,... Every year, thousands of children around the world are born with rare genetic diseases leading to death or lifelong disability. With technological advancements in the field of genetics and medicine, the rate of introduction of treatments for these rare conditions has grown remarkably. However, timing is of great importance for medication administration. The benefit that can be measured in a patient who has already suffered from a long irreversible degenerative disorder is small and, sometimes, it hardly justifies the cost and the burden of the treatment. Early diagnosis is, thus, of primary importance both to obtain the best effect of the innovative medications and to accelerate their development. The investigators are pioneered in the field of genetic newborn screening (NBS) in rare diseases by funding, designing, and leading an innovative genetic NBS program initiated in March 2018 in Southern Belgium for Spinal Muscular Atrophy (SMA) that allowed, so far, for 11 children to be detected and treated early and avoid the terrible fate of the disease. The program was disseminated in 17 countries and included public dissemination and health-economic analysis since the very beginning \[1\]. (www.facebook.com/sunmayariseonsma). Drawing upon our experience with SMA screening, the investigators have designed a project to screen up to 40,000 newborns/year progressively in 3 years for virtually all the rare diseases that can benefit from treatment or a pre-symptomatic clinical trial. The methodology of Baby Detect includes sequencing of target genes on dried blood spots collected from the NBS cards in a timely and cost-efficient manner, and its high dynamicity allows for any newly treatable rare disease to be included in its scheme in no longer than 6 months. Baby Detect, as a multidisciplinary newborn screening program, involves expertise in areas from genetics and medicine to laboratory studies, computer science, Data Protection, Ethics, and health economy. It will constitute the proof of concept that is needed before moving to a whole region-scale population. More |
NCT02065869 :
Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
(Terminated) Locations: Roma, Italy, London, United Kingdom, London, United Kingdom, Newcastle upon Tyne, United Kingdom Roma, Italy, London, United Kingdom, London, United Kingdom, Newcastle upon Tyne, United Kingdom Study Dates: Start: April 1, 2014 Study Overview: This is a Phase I/II study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant... This is a Phase I/II study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic disorders, with the potential for reducing the severity and duration severe acute graft versus host disease (GvHD). The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD who progress or do not respond to standard of care treatment. More |
NCT03206086 :
Eltrombopag for People With Fanconi Anemia
(Active, Not Recruiting) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: November 2, 2018 | Estimated Completion Date: August 1, 2028 Study Overview: Fanconi anemia (FA) is a rare genetic disease that often presents as a bone marrow failure (BMF) syndrome but also can affect any other organ. Etiologically, loss of function mutations in more than... Fanconi anemia (FA) is a rare genetic disease that often presents as a bone marrow failure (BMF) syndrome but also can affect any other organ. Etiologically, loss of function mutations in more than 21 different gene members of the FA core complex (i.e. FANCA-FANCV) have been associated with FA. The FA core complex is involved in interstrand cross-link DNA damage repair during cell division. Impaired DNA repair causes genomic instability which consequently can cause apoptosis of the cell or malignant transformation. In addition to impaired DNA repair mechanisms, FA cells exhibit increased sensitivity to pro-inflammatory cytokines (e.g. IFN-gamma, TNF-alpha) and elevated levels of these cytokines have been associated with bone marrow failure in subjects with FA and other inherited bone marrow failure syndromes. Patients with FA may present with congenital anomalies, such as microcephaly or short stature. However, the failure of the hematopoietic stem cell (HSC) compartment to produce sufficient numbers of peripheral blood cells, and progression to myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) are the greatest risk factors for morbidity and mortality, particular in young patients with FA. In a few reported cases, spontaneous somatic reversion of inherited mutations has resulted in a selective growth advantage of corrected HSCs that subsequently restored hematopoiesis. However, therapeutic options are limited in FA. Although HSC transplantation outcomes have significantly improved over the past two decades, donor availability, graft failure, and FA-specific transplant toxicities are still significant hurdles towards a curative treatment of FA-associated BMF. Moreover, attempts at genetic correction of FA are not yet ready for patient care. The thrombopoietin (TPO) mimetic eltrombopag (EPAG) has recently been shown to be effective in restoring tri-lineage hematopoiesis in patients with treatment refractory acquired severe aplastic anemia (SAA). Of particular interest for patients with FA is the observation that EPAG also improves the repair of double strand DNA breaks, a mechanism that is impaired in patients with FA. Additionally, our pre-clinical studies indicate that EPAG evades INF-gamma blockade of signal transduction from the TPO receptor (cMPL) resulting in improved survival and proliferation of HSCs. Based on these clinical and pre-clinical studies, we hypothesize that EPAG will improve peripheral blood cell counts in patients with FA and thus reduce morbidity and mortality. This phase II clinical trial proposes to treat patients with FA for 6 months with EPAG to assess safety and efficacy at improving hematological manifestations of FA. Responders at 6 months will be able to continue EPAG on the extension part of this protocol for an additional 3 years. During this time frame we anticipate further improvement of peripheral blood cells counts that will eventually result in the discontinuation of EPAG after a tapering period. Translational studies will explore EPAG effects on DNA repair activity, apoptosis, global transcriptome and TPO signaling pathways in patient s hematopoietic stem and progenitor cells (HSPCs). More |
NCT00987480 :
Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
(Completed) Locations: Boston, United States, New York, United States, New York, United States, Cincinnati, United States, Seattle, United States, Milwaukee, United States Boston, United States, New York, United States, New York, United States, Cincinnati, United States, Seattle, United States, Milwaukee, United States Study Dates: Start: September 25, 2009 | Actual Completion Date: July 10, 2017 Study Overview: No description available. No description available. |
NCT01346761 :
Risk Education and Assessment for Cancer Heredity
(Completed) Locations: Salt Lake City, United States Salt Lake City, United States Study Dates: Start: August 1, 2009 | Actual Completion Date: December 1, 2012 Study Overview: Following confirmation of eligibility and completion of baseline surveys, participants will be randomly assigned to one of the study arms by the project coordinator, using a computer-generated... Following confirmation of eligibility and completion of baseline surveys, participants will be randomly assigned to one of the study arms by the project coordinator, using a computer-generated allocation algorithm on the basis of a randomization blocks method using four, six or eight participants in each block. In-person and telephone counseling will be delivered by the same board-certified genetic counselors using a guideline-concordant semi-structured protocol that will allow for personalization of counseling. Participants randomly assigned to telephone counseling will be mailed packets that include a sealed envelope containing an educational brochure about hereditary breast and ovarian cancer genetic counseling with visual aids. At the time of their session, participants will review the brochure and genetic counselors will use visual aids to explain breast-ovarian cancer genetics. Women receiving in-person counseling will be given the same materials during their session at the community clinic. For women who elect to have testing, those who have telephone counseling will be sent a genetic test kit; those who have in-person counseling will have the option of giving a sample immediately at the clinic, or will be given a test kit with the same instructions as those in the telephone-counseling group. When BRCA test results become available, participants will be offered individual post-test counseling with the same genetic counselor who conducted the pretest session. More |
NCT03889171 :
Comparison to Psychological, Medical and Emotional Influencing Communication and Achievement Factors to Oncogenetics Tests
(Completed) Locations: Not specified Not specified Study Dates: Start: August 1, 2012 | Actual Completion Date: September 1, 2018 Study Overview: The risk associated with a genetic predisposition is among the various forms of risk, the strongest identifiable risk . It enables to offer people at risk an appropriate medical care (screening,... The risk associated with a genetic predisposition is among the various forms of risk, the strongest identifiable risk . It enables to offer people at risk an appropriate medical care (screening, prevention ) the clinical benefit is validated today. The person with whom a predisposing mutation has been identified must communicated its related information on the risk of cancer and the ability to perform genetic analysis. It appears that this dissemination of information is not always optimal, as shown in figures from the National Cancer Institute joined the project; the purpose of the study was to analyze the psychological and emotional determinants of domestic dissemination of information about genetic risk of cancer and to compare the level of diffusion syndromes in breast/ ovarian cancer ( BRCA1 / BRCA2) and colon/endometrial ( HNPCC ) |
NCT00001806 :
Methods in Education for Breast Cancer Genetics
(Completed) Locations: Bethesda, United States Bethesda, United States Study Dates: Start: April 6, 1999 | Actual Completion Date: December 6, 2017 Study Overview: In October 1995 the National Naval Medical Center opened the only Department of Defense funded Breast Care Center (BCC). Within less than one year the Center was seeing 100 - 200 new patients per... In October 1995 the National Naval Medical Center opened the only Department of Defense funded Breast Care Center (BCC). Within less than one year the Center was seeing 100 - 200 new patients per week and making 10 - 20 new diagnoses of breast cancer per month. In 1997 we began conducting germline testing for BRCA1 and BRCA2 under an approved Navy IRB study. To date, 51 individuals have enrolled into the Education and Counseling component, and 42 individuals have elected to receive germline testing. Early on it became apparent that a more time efficient approach to education and counseling would be required if access to information on breast cancer genetics was to be made available to a larger population. Traditionally, education and counseling has been offered on a one to one basis prior to germline testing. Often, hours are spent with an individual. At some centers, multiple visits are standard. Not only is there a shortage of health care providers trained in cancer genetics, but even if there were an abundance of trained providers, the time and cost, as well as need for efficiency would preclude this type of approach. Thus, this approach is not applicable to most health care delivery systems. We began offering education in small groups approximately 18 months ago, using the same informational content that we use in our one to one sessions. Based on preliminary, nonrandomized results, there appeared to be no difference in learning and general patient satisfaction based on results of pre- and post-test administered before and after the education. It was our contention that group education is equivalent, and in some situations better than individual education. Therefore, we will conduct a randomized trial designed to test equivalence between individual and group education. |
NCT01316549 :
Study of Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation
(Completed) Locations: San Francisco, United States San Francisco, United States Study Dates: Start: January 1, 2011 | Actual Completion Date: April 30, 2016 Study Overview: Fludarabine is a nucleoside analog with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote... Fludarabine is a nucleoside analog with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote stem cell engraftment. This is a single-center, pharmacokinetic-pharmacodynamic (PK-PD) study investigating the clinical pharmacology of fludarabine in 45 children undergoing alloHCT at University of California, San Francisco Benioff Children's Hospital. Patients would receive fludarabine regardless of whether or not they decide to consent to PK sampling. Fludarabine doses will not be adjusted based on PK data. We will apply the combination of a D-optimality-based limited sampling strategy and population PK methodologies to determine specific factors influencing fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships. Subjects will undergo PK sampling of plasma (f-ara-a) and intracellular (f-ara-ATP) drug concentrations over the duration of fludarabine therapy (3 to 5 days). To evaluate sources of variability impacting fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling. A single blood draw for the collection of DNA and genotyping of single nucleotide polymorphisms of genes involved in fludarabine activation, transport or elimination will occur in all patients. To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant. More |
NCT00586274 :
Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT
(Terminated) Locations: Houston, United States, Houston, United States Houston, United States, Houston, United States Study Dates: Start: March 1, 2002 Study Overview: Patients will have received a haplo-identical stem cell transplant on our on-going study "CD45 (YTH-24 and YTH-54) and CD52 (Campath 1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor... Patients will have received a haplo-identical stem cell transplant on our on-going study "CD45 (YTH-24 and YTH-54) and CD52 (Campath 1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients with Fanconi Anemia" (H-9938 IND# 7233) and will become eligible to receive allodepleted T Cells following engraftment. What follows is a summary of the treatment plan including initial transplant phase as well as generation and infusion of allodepleted T cells. Preparative Regimen for Patients with Fanconi Anemia: The study will be open to patients who received a haploidentical PBSCT on the MAFIA protocol and for patients who failed to engraft and receive a second haploidentical transplants with alternate conditioning consisting of ATG, Fludarabine, TBI (450cGY single dose) and Cytoxan. In Outline MAFIA conditioning (primary conditioning regimen) Day 8 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 7 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 6 Campath 1H 10mg iv over 4hr Fludarabine 30 mg/m2 5 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2 * 4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2
* 3 YTH 24/54 400ug/kg over 6 hr
* 2 YTH 24/54 400ug/kg over 6 hr
* 1 Rest
* 0 CD34-selected PBSC infusion Stem Cell Infusion: One day after the completion of pretransplant conditioning therapy (day 0), CD34+ cells will be infused through a central venous catheter as outlined in CAGT SOPs. This study will begin with a dose of T cells known not to cause GvHD even in haploidentical recipients, even when the T cells administered have not first been allodepleted. Dose escalation will follow a traditional up and down method, but as results become available they will be used to determine subsequent dose levels by the continual reassessment method. Initially, 2 patients will be entered beginning at dose level 1. Each and every patient will receive up to three additional injections of T cells at the same dose, at monthly intervals, provided there is no evidence of grade 2 or higher GVHD, until total T cell numbers are \> 1000/ul. Dose level -1 (1 x 10\^3 T cells/Kg); Dose level 1 (1 x 10\^4 T cells/Kg); Dose level 2 (1 x 10\^5 T cells/Kg); Dose level 3 (1 x 10\^6 T cells/Kg); Dose level 4 (5 x 10\^6 T cells/Kg) More |
NCT00027274 :
Cancer in Inherited Bone Marrow Failure Syndromes
(Recruiting) Locations: Bethesda, United States, Rockville, United States Bethesda, United States, Rockville, United States Study Dates: Start: November 28, 2001 Study Overview: Study Description: Study Description: This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of medical records, cancer surveillance. A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders. Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers. This study will determine whether patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer. These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer. Carriers of IBMFS gene pathogenic variant(s) are at increased risk of cancer. The prototype disorder is Fanconi Anemia (FA); other IBMFS will also be studied. Objectives: To determine the types and incidence of specific cancers in patients with an IBMFS. To investigate the relevance of IBMFS gene pathogenic variants in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers. To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s). To determine the risk of cancer in IBMFS carriers. Endpoints: Primary Endpoint: -All cancers, solid tumors, and cancers specific to each type of IBMFS. Secondary Endpints: -Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones. More |
NCT03609840 :
Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients
(Completed) Locations: San Francisco, United States San Francisco, United States Study Dates: Start: May 24, 2017 | Actual Completion Date: July 31, 2023 Study Overview: Thiotepa is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric hematopoietic cell transplantation (HCT) to promote stem cell... Thiotepa is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric hematopoietic cell transplantation (HCT) to promote stem cell engraftment. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, TEPA. This is a single-center, prospective, non-interventional pharmacokinetics (PK) study investigating the clinical pharmacology of thiotepa and TEPA in 60 children undergoing hematopoietic stem cell transplant (HCT) at University of California, San Francisco Benioff Children's Hospital. Patients would receive thiotepa regardless of whether or not they decide to consent to PK sampling. Thiotepa doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing thiotepa and TEPA exposure in pediatric HCT recipients. Population PK methodologies support the use of sparse sampling and therefore allow the investigators to investigate drug levels in a pediatric population that would otherwise not be feasible using traditional intensive PK sampling. Subjects will undergo PK sampling of plasma thiotepa and TEPA drug concentrations over the duration of thiotepa therapy (3 to 5 days). To evaluate sources of variability impacting thiotepa and TEPA exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling. A single blood draw for the collection of DNA and genotyping of single nucleotide polymorphisms of genes involved in fludarabine activation, transport or elimination will occur in all patients. To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant. More |
NCT04248439 :
Gene Therapy for Fanconi Anemia, Complementation Group A
(Active, Not Recruiting) Locations: Stanford, United States, Minneapolis, United States Stanford, United States, Minneapolis, United States Study Dates: Start: July 15, 2020 | Estimated Completion Date: May 1, 2026 Study Overview: This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector... This is a pediatric open-label Phase II clinical trial to assess the efficacy of a hematopoietic gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral vector carrying the FANCA gene in subjects with FA-A. Enriched CD34+ hematopoietic stem cells will be transduced ex vivo with the therapeutic lentiviral vector and infused via intravenous infusion following transduction without any prior conditioning. More |
NCT07005297 :
Clinical Genetics Branch Eligibility Screening Survey
(Not Yet Recruiting) Locations: Rockville, United States Rockville, United States Study Dates: Start: October 13, 2025 | Estimated Completion Date: January 1, 2036 Study Overview: Study Description: Study Description: This protocol will be utilized for the creation and management of an eligibility screening survey for patients who are interested in enrolling in a study being conducted by the Clinical Genetics Branch (CGB). Objectives: The primary objective of this protocol is to establish a database of eligibility data collected from prospective participants who have completed an eligibility screening survey. This database, managed by the CGB, will serve as a critical resource for assessing participant eligibility for enrollment in various CGB studies. More |