Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT ID: NCT00453388
Last Updated: 2020-01-29
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
6 participants
INTERVENTIONAL
2007-02-28
2013-06-30
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Cyclophosphamide
Given IV
Cyclosporine
Given IV or PO
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Mycophenolate Mofetil
Given PO
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic stem cell transplant
Total-Body Irradiation
Undergo TBI
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.
Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Cyclophosphamide
Given IV
Cyclosporine
Given IV or PO
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Mycophenolate Mofetil
Given PO
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic stem cell transplant
Total-Body Irradiation
Undergo TBI
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.
Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Cyclophosphamide
Given IV
Cyclosporine
Given IV or PO
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Mycophenolate Mofetil
Given PO
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic stem cell transplant
Total-Body Irradiation
Undergo TBI
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.
Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Cyclophosphamide
Given IV
Cyclosporine
Given IV or PO
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Mycophenolate Mofetil
Given PO
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic stem cell transplant
Total-Body Irradiation
Undergo TBI
Interventions
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Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Cyclophosphamide
Given IV
Cyclosporine
Given IV or PO
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Mycophenolate Mofetil
Given PO
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic stem cell transplant
Total-Body Irradiation
Undergo TBI
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Fred Hutchinson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Hans-Peter Kiem
Role: PRINCIPAL_INVESTIGATOR
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Locations
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Children's Hospital and Research Center at Oakland
Oakland, California, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Universidade Federal do Paraná
Curitiba, Paraná, Brazil
Countries
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Other Identifiers
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NCI-2010-00238
Identifier Type: REGISTRY
Identifier Source: secondary_id
2064.00
Identifier Type: OTHER
Identifier Source: secondary_id
2064.00
Identifier Type: -
Identifier Source: org_study_id
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