at Oakland, California and other locations
study started



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 mofetil, and cyclosporine in treating patients with Fanconi anemia (FA). Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and TBI before or after a donor bone marrow transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.

Official Title

Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study



  1. 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.


  1. 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.


Acute Myeloid Leukemia in Remission de Novo Myelodysplastic Syndrome Fanconi Anemia Previously Treated Myelodysplastic Syndrome Preleukemia Fanconi Syndrome Anemia Myelodysplastic Syndromes Syndrome Vidarabine Cyclosporine Mycophenolic Acid Cyclophosphamide Fludarabine Fludarabine phosphate Cyclosporins Allogeneic Bone Marrow Transplantation Laboratory Biomarker Analysis Mycophenolate Mofetil Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Total-Body Irradiation


You can join if…

  • Any patient with FA and bone marrow (BM) failure involving 2 of the following 3 lineages: granulocyte count < 0.5 x 109/L, platelet count < 20 x 109/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

You CAN'T join if...

  • 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 108 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


  • Children's Hospital and Research Center at Oakland
    Oakland California 94609-1809 United States
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    Seattle Washington 98109 United States


in progress, not accepting new patients
Start Date
Fred Hutchinson Cancer Research Center
Phase 2
Study Type
Last Updated