Donor Stem Cell Transplant or Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia in Remission
Condition: Leukemia
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving chemotherapy before a donor bone marrow or peripheral blood stem cell
      transplant helps stop the growth of cancer cells. It also helps stop the patient's immune
      system from rejecting the donor's stem cells. When the healthy stem cells from a donor are
      infused into the patient they may help the patient's bone marrow make stem cells, red blood
      cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can
      make an immune response against the body's normal cells. Giving cyclosporine and methotrexate
      before and after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well donor stem cell transplant or bone marrow
      transplant works in treating patients with acute myeloid leukemia in remission.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) or
           bone marrow transplantation (BMT) from a HLA-matched sibling donor, HLA-matched
           unrelated donor, or HLA-mismatched familial donor, in terms of the frequency of relapse
           and duration of remission, in patients with acute myeloid leukemia (AML) who have either
           achieved complete remission (CR1) after induction chemotherapy or who experienced
           recurrent AML then achieved second CR (CR2) after salvage chemotherapy.

      Secondary

        -  Determine the engraftment, donor chimerism, and secondary graft failure in these
           patients.

        -  Assess acute and chronic graft-vs-host disease, immune recovery, and infections in these
           patients.

        -  Determine transplantation-related mortality, leukemia-free survival, and overall
           survival of these patients.

      OUTLINE:

        -  Conditioning chemotherapy and allogeneic bone marrow or hematopoietic stem cell
           transplantation (HSCT): After completion of induction chemotherapy and a resulting
           complete response (CR1) or salvage chemotherapy resulting in CR2, patients receive 1 of
           the following conditioning regimens and transplantations determined by age,
           co-morbidity, and type of available donor:

             -  15 to 55 years of age without significant co-morbidity* undergoing HLA-matched
                sibling bone marrow transplantation (BMT) (BuCy conditioning): Patients receive
                busulfan IV once daily on days -7 to -4 and cyclophosphamide IV over 1-2 hours once
                daily on days -3 and -2. Patients then undergo an allogeneic BMT on day 0.

             -  Older than 55 years or younger than 55 years with co-morbidity* undergoing
                HLA-matched sibling BMT; patients of any age undergoing HLA-matched unrelated HSCT;
                and for patients of any age undergoing HLA-mismatched familial donor HSCT (BuFluATG
                conditioning): Patients receive busulfan IV once daily on days -7 and -6,
                fludarabine phosphate IV over 30 minutes once daily on days -7 to -2,
                anti-thymocyte globulin IV over 4 hours once daily on days -3 to -1, and
                methylprednisolone IV over 30 minutes once daily on days -4 to -1. Patients then
                undergo either an allogeneic BMT on day 0 or allogeneic peripheral blood
                hematopoietic stem cell infusions on days 0-1 or 0-2.

      NOTE: *Significant co-morbidity is defined as residual fungal or other infections in the lung
      or other viscera and residual organ toxicities occurring during induction or consolidation
      chemotherapy.

        -  GVHD prophylaxis: Patients receive cyclosporine orally or IV over 2-4 hours twice daily
           beginning on day -1 followed by a taper starting on day 30 (BuFluATG conditioning) or
           day 60 (BuCy conditioning). Patients also receive methotrexate IV on days 1, 3, and 6
           after the last day of donor cell infusion.

        -  CNS prophylaxis: Patients receive intrathecal (IT) methotrexate once before conditioning
           regimen. Patients receive IT methotrexate once every 2 weeks for 3 times after
           transplantation and platelet recovery. Patients also receive leucovorin calcium orally
           or IV over 4 hours after IT methotrexate and then once every 6 hours for a total of 8
           doses after each dose of IT methotrexate.

      After completion of study therapy, patients are followed every 3 months for 3 years and then
      annually.
    

Intervention name(s): anti-thymocyte globulin; busulfan; cyclophosphamide; cyclosporine; fludarabine phosphate; methotrexate; allogeneic hematopoietic stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Busulfan; Methotrexate; Fludarabine; Fludarabine phosphate; Cyclosporins; Antilymphocyte Serum
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with del(5q); adult acute myeloid leukemia with t(16;16)(p13;q22); recurrent adult acute myeloid leukemia; adult acute myeloid leukemia in remission; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; adult acute minimally differentiated myeloid leukemia (M0); childhood acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); childhood acute myeloblastic leukemia with maturation (M2); adult acute myelomonocytic leukemia (M4); childhood acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); childhood acute erythroleukemia (M6); adult acute megakaryoblastic leukemia (M7); childhood acute megakaryocytic leukemia (M7)