Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
Condition: Fanconi Anemia
MeSH terms: Fanconi Syndrome; Anemia; Fanconi Anemia
Intervention: anti-thymocyte globulin; filgrastim; busulfan; cyclophosphamide; fludarabine phosphate; methylprednisolone; Hematopoietic stem cell transplantation
Intervention description: Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.; given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10^9/L); Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if <4 years old); 10 mg/kg intravenously (IV) on Days -5 through -2.; 35 mg/m^2 intravenously (IV) on Days -5 through -2.; 1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.; Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.
Intervention MeSH terms: Methylprednisolone; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Maximum age: 44 Years
Healthy volunteers: No
Keywords: Fanconi anemia

Summary:

      RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace
      blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy
      before a donor stem cell transplant may make the transplant more likely to work. This may be
      an effective treatment for patients with high risk Fanconi's anemia.

      PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating
      high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be <45 years of age with a diagnosis of Fanconi anemia with:

               -  Biallelic BRCA2 mutations, or

               -  Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5%
                  blasts), or acute leukemia who are ineligible for total body irradiation.
                  Aplastic anemia is defined as having at least one of the following (with or
                  without cytogenetic abnormalities): platelet count <20 * 10^9, - absolute
                  neutrophil count (ANC) <5 * 10^8/L, - Hgb <8 g/dL

          -  Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or
             unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen
             mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors
             will be typed for HLA-A and B using serological level typing and for DRB1 using high
             resolution molecular typing.

          -  Adequate major organ function including:

               -  Cardiac: ejection fraction >45%

               -  Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no
                  cirrhosis)

               -  Karnofsky performance status >70% or Lansky >50%

          -  Women of child bearing potential must be using adequate birth control and have a
             negative pregnancy test.

        Exclusion Criteria:

          -  Active CNS leukemia at time of HSCT.

          -  Active uncontrolled infection within one week of hematopoietic stem cell transplant
             (HSCT).

          -  Pregnant or lactating female.

        Donor Inclusion Criteria:

          -  Donor must be in good health based on review of systems and results of physical
             examination.

          -  Donor must have a normal hemoglobin, white count, platelet count and partial
             thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.

          -  HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative.

          -  Female donors of childbearing potential must have a negative pregnancy test.

          -  Unrelated donors must agree to peripheral blood stem cell (PBSC) donation

        Donor Exclusion Criteria:

          -  Donor is a lactating female.