Clinical Trial: Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor peripheral blood, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of busulfan, antithymocyte globulin, and fludarabine when given together with a donor stem cell transplant in treating young patients with blood disorders, bone marrow disorders, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.


Detailed Summary:

OBJECTIVES:

Primary

  • Determine the efficacy, in terms of graft rejection at 4 weeks, of a conditioning regimen comprising busulfan, anti-thymocyte globulin, and fludarabine followed by donor stem cell transplantation (SCT) in children with stem cell defects, marrow failure syndromes, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
  • Determine the pharmacokinetics of busulfan in children undergoing donor SCT.

Secondary

  • Determine the toxicity of this regimen in these patients.
  • Determine engraftment at 3, 6, 9, and 12 months and mixed chimerism in patients treated with this regimen.
  • Determine overall and disease-free survival of patients treated with this regimen.

OUTLINE: Patients receive one of the following cytoreductive regimens:

  • Regimen 1 (patients with an HLA genotypic matched sibling donor): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, fludarabine IV on days -5 to -2, and anti-thymocyte globulin (ATG) IV over 10 hours on days -3 to -1.
  • Regimen 2 (patients with an HLA closely matched related [not genotypic] or unrelated donor): Patients receive busulfan and fludarabine as in regimen 1, and ATG IV over 10 hours on days -4 to -1.
  • Regimen 3 (patients with Fanconi's anemia or severe aplastic anemia with genotypic matched sibling donor): Patients receive fludarabine as in r
    Sponsor: University of California, San Francisco

    Current Primary Outcome: Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation

    Original Primary Outcome:

    Current Secondary Outcome:

    • Toxicity grades 3 or 4 assessed from conditioning through 1 year post transplantation
    • Engraftment at 1, 3, 6, 9, and 12 months post transplantation
    • Mixed chimerism at 1, 3, 6, 9, and 12 months post transplantation
    • Survival measured from the day of first dose of conditioning
    • Disease-free survival measured from the day of first dose of conditioning


    Original Secondary Outcome:

    Information By: University of California, San Francisco

    Dates:
    Date Received: March 21, 2006
    Date Started: August 2000
    Date Completion:
    Last Updated: November 8, 2012
    Last Verified: November 2012