Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematological Cancer
Condition: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving chemotherapy before a donor bone marrow stem cell transplant helps stop the
      growth of cancer cells. Chemotherapy and antithymocyte globulin 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 cyclosporine and methotrexate after transplant may
      stop this from happening.

      PURPOSE: This phase II trial is studying how well giving donor stem cell transplant together
      with busulfan, fludarabine, and antithymocyte globulin works in treating patients with
      hematological cancer.
    

Detailed description: 
      OBJECTIVES:

        -  To investigate whether unrelated donor hematopoietic stem cell transplantation using a
           nonmyeloablative conditioning regimen comprising busulfan, fludarabine phosphate, and
           anti-thymocyte globulin can reduce treatment-related mortality in patients with
           hematologic malignancies.

        -  To investigate whether this regimen can be sufficiently immunosuppressive to enable
           engraftment of HLA-matched unrelated hematopoietic stem cells.

      OUTLINE: This is a multicenter study.

      Prior to receiving the conditioning chemotherapy regimen, all patients with acute leukemia,
      chronic myelogenous leukemia (CML), and high-risk myelodysplastic syndromes (chronic
      myelomonocytic leukemia, atypical CML, and refractory anemia with excess blasts) receive one
      dose of intrathecal (IT) methotrexate. These patients also receive leucovorin calcium IV or
      orally 4 hours after IT methotrexate and every 6 hours for a total of 8 doses.

        -  Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30
           minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -6, anti-thymocyte
           globulin IV over 4 hours on days -4 to -2.

        -  Allogeneic bone marrow stem cell transplantation (SCT): Patients undergo allogeneic bone
           marrow SCT on day 0.

        -  Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (CSA) IV
           over 2-4 hours every 12 hours starting on day -1 and continuing until day 180 (CSA can
           be given orally every 12 hours once oral medication can be tolerated) and methotrexate
           IV on days 1, 3 , 6 , and 11.

      Once blood counts recover, patients with acute leukemia or CML in blast crisis resume IT
      methotrexate once every 2 weeks for a total of 3 doses. Patients also receive leucovorin
      calcium IV or orally 4 hours after IT methotrexate and then every 6 hours for a total of 8
      doses.

      Patients are followed for at least 10 years after SCT.
    

Intervention name(s): anti-thymocyte globulin; busulfan; fludarabine phosphate; leucovorin calcium; methotrexate; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure
Intervention MeSH terms: Leucovorin; Methotrexate; Fludarabine phosphate; Fludarabine; Busulfan; Calcium; Antilymphocyte Serum; Levoleucovorin
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia; adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; untreated adult acute myeloid leukemia; acute lymphocytic leukemia; secondary acute myeloid leukemia; acute undifferentiated leukemia; mast cell leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; meningeal chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic myelomonocytic leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts