Status:
COMPLETED
Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
Lead Sponsor:
Fred Hutchinson Cancer Center
Collaborating Sponsors:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Conditions:
Acute Myeloid Leukemia in Remission
de Novo Myelodysplastic Syndrome
Eligibility:
All Genders
Phase:
PHASE2
Brief Summary
This phase II trial studies how well total-body irradiation (TBI) works when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofe...
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. ...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
February 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 1 2013
Estimated Enrollment :
6 Patients enrolled
Trial Details
Trial ID
NCT00453388
Start Date
February 1 2007
End Date
June 1 2013
Last Update
January 29 2020
Active Locations (5)
Enter a location and click search to find clinical trials sorted by distance.
1
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
2
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
3
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
4
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53201