- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00453388
Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Paraná
-
Curitiba, Paraná, Brazil, 80060-000
- Universidade Federal do Parana
-
-
-
-
California
-
Oakland, California, United States, 94609-1809
- Children's Hospital and Research Center at Oakland
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53201
- Children's Hospital of Wisconsin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Any patient with FA and bone marrow (BM) failure involving 2 of the following 3 lineages: granulocyte count < 0.5 x 10^9/L, platelet count < 20 x 10^9/L, or hemoglobin < 8 g/dL
- Any patient with FA who requires red blood cell or platelet transfusions because of marrow failure
- Any patient with FA who has a life-threatening BM failure involving a single hematopoietic lineage
- Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in morphological remission (defined as absence of circulating blasts and bone marrow blasts < 5% as assessed by morphology); Note that hematopoietic recovery is not required for remission status
- Patients must have a negative cytotoxic cross match with donor
- DONOR: Related, human leukocyte antigen (HLA)-haploidentical donors must be identical for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1 loci of the unshared haplotype
- DONOR: Unrelated, HLA-matched donors must be matched at HLA-A, B, C, DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing at the highest resolution routinely available at the time of donor selection; a single allele mismatch at HLA-A, B, or C is allowed OR a single DQB1 mismatch is allowed
- DONOR: Bone marrow will be the only allowed hematopoietic stem cell source
- DONOR: Haploidentical donor selection will be based on standard institutional criteria, otherwise no specific prioritization will be made amongst the suitable available donors
Exclusion Criteria:
- Patients having available HLA-matched related donors
- Significant organ dysfunction that would prevent compliance with conditioning, graft-versus-host disease (GVHD) prophylaxis, or would severely limit the probability of survival, such as liver disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or cardiac disease (ejection fraction < 35%, or if unable to obtain ejection fraction, shortening fraction of < 26%; if shortening is < 26% a cardiology consult is required with principal investigator [PI] having final approval of eligibility)
- Human immunodeficiency virus (HIV) seropositive patients
- Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding
- Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment
- AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow blasts >= 5% as assessed by morphology
- Active infectious disease concerns
- Karnofsky performance score < 50 or Lansky performance score < 40
- DONOR: Donors found to have Fanconi anemia based on chromosomal breakage analysis
- DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) or who are unwilling to be bone marrow donors
- DONOR: HIV-positive donors
- DONOR: Donors who are cross-match positive with recipient
- DONOR: Recipient homozygous at mismatched locus; if the recipient is homozygous at HLA-A, B, or C and the donor is mismatched at that locus, the donor should be avoided; exceptions must be discussed with the PI
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm I (2 vs 2.5 vs 3 Gy TBI dose-escalation)
Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic bone marrow transplant
Other Names:
Undergo allogeneic stem cell transplant
Other Names:
|
EXPERIMENTAL: Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI de-escalation)
Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic bone marrow transplant
Other Names:
Undergo allogeneic stem cell transplant
Other Names:
|
EXPERIMENTAL: Arm III (2 vs 2.5 vs 3 Gy TBI dose-escalation)
Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic bone marrow transplant
Other Names:
Undergo allogeneic stem cell transplant
Other Names:
|
EXPERIMENTAL: Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI de-escalation)
Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic bone marrow transplant
Other Names:
Undergo allogeneic stem cell transplant
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Who Engraft at Each Dose of TBI Used
Time Frame: Up to Day 200
|
Number of subjects who engrafted.
Engraftment defined as greater than 95% donor chimerism.
|
Up to Day 200
|
Incidence of Grades III-IV Acute GVHD
Time Frame: Up to Day 100
|
Number of subjects who developed maximum grade acute graft-vs-host disease aGVHD Stages Skin:
Liver:
Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death |
Up to Day 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Transplant-related Mortality
Time Frame: Up to Day 200
|
Number of subjects who expired due to transplant-related mortality
|
Up to Day 200
|
Incidence of Adverse Events
Time Frame: Up to Day 100
|
Number of subjects who developed reportable AEs, assessed using adapted version of the Common Toxicity Criteria
|
Up to Day 100
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hans-Peter Kiem, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Neoplasms
- Kidney Diseases
- Urologic Diseases
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- DNA Repair-Deficiency Disorders
- Precancerous Conditions
- Anemia, Hypoplastic, Congenital
- Anemia, Aplastic
- Congenital Bone Marrow Failure Syndromes
- Bone Marrow Failure Disorders
- Renal Tubular Transport, Inborn Errors
- Syndrome
- Myelodysplastic Syndromes
- Preleukemia
- Anemia
- Fanconi Syndrome
- Fanconi Anemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Cyclophosphamide
- Fludarabine
- Fludarabine phosphate
- Mycophenolic Acid
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 2064.00 (OTHER: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2010-00238 (REGISTRY: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Previously Treated Myelodysplastic Syndrome
-
Brian JonasNational Cancer Institute (NCI); Celgene; Pharmacyclics LLC.CompletedPreviously Treated Myelodysplastic Syndrome | Myelodysplastic Syndrome | Therapy-Related Myelodysplastic Syndrome | Secondary Myelodysplastic Syndrome | Refractory High Risk Myelodysplastic SyndromeUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)TerminatedPreviously Treated Myelodysplastic SyndromesUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
-
National Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingPreviously Treated Myelodysplastic Syndrome | Myelodysplastic Syndrome | Aplastic Anemia | de Novo Myelodysplastic SyndromeUnited States
-
Weill Medical College of Cornell UniversityJazz PharmaceuticalsCompletedMyelodysplastic Syndromes | Leukemia, Myeloid, Acute | Leukemia, Relapsed Adult Acute Myeloid | Myelodysplastic Syndromes, Previously TreatedUnited States
-
Shanghai Junshi Bioscience Co., Ltd.CTI Clinical Trial and Consulting Services; TopAlliance Biosciences, Inc.WithdrawnMalignancies | Previously Treated, Advanced
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndrome | Recurrent Adult Acute Myeloid LeukemiaUnited States
-
Mentrik Biotech, LLCUnknownPreviously Treated CD20+ B-cell MalignanciesUnited States
-
National Cancer Institute (NCI)CompletedAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome | Chronic Myelomonocytic Leukemia | Previously Treated Myelodysplastic Syndrome | Recurrent Adult Acute Myeloid Leukemia | Myelodysplastic Syndrome | Secondary Myelodysplastic SyndromeUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States