Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
Condition: Acute Myeloid Leukemia in Remission; de Novo Myelodysplastic Syndrome; Fanconi Anemia; Previously Treated Myelodysplastic Syndrome
MeSH terms: Preleukemia; Fanconi Syndrome; Anemia; Myelodysplastic Syndromes; Fanconi Anemia; Syndrome
Intervention: Allogeneic Bone Marrow Transplantation; Cyclophosphamide; Cyclosporine; Fludarabine Phosphate; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Total-Body Irradiation
Intervention description: Undergo allogeneic bone marrow transplant; Given IV; Given IV or PO; Given IV; Correlative studies; Given PO; Undergo allogeneic stem cell transplant; Undergo TBI
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Healthy volunteers: No

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 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.
    

Eligibility criteria:

        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