Treatment of Bone Marrow to Prevent Graft-Versus-Host Disease in Patients With Acute or Chronic Leukemia Undergoing Bone Marrow Transplantation
Condition: Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Graft vs Host Disease; Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      RATIONALE: Bone marrow that has been treated to remove certain white blood cells may reduce
      the chance of developing graft-versus-host disease following bone marrow transplantation.

      PURPOSE: Randomized phase II/III trial to compare the effectiveness of treated bone marrow
      with that of untreated bone marrow in preventing graft-versus-host disease in patients with
      acute or chronic leukemia who are undergoing bone marrow transplantation.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the efficacy of processed (cell depleted) vs unprocessed (conventional)
           unrelated bone marrow transplantation in reducing grade III/IV acute graft vs host
           disease (GVHD) in patients with acute or chronic leukemia or myelodysplastic syndromes.

        -  Compare the safety of these regimens in these patients.

        -  Compare the disease-free survival rate at 100 days and at 6 months in patients treated
           with these regimens.

        -  Compare the time to engraftment and percent engraftment in patients treated with these
           regimens.

        -  Compare the reduction rate of grade II or greater acute and chronic GVHD in patients
           treated with these regimens.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to degree of HLA matching and disease (chronic vs acute). Acute myelogenous
      leukemia patients are further stratified according to prior myelodysplastic syndromes (yes vs
      no). Patients are randomized to one of two bone marrow transplantation arms.

      All patients receive a conditioning regimen comprising fludarabine IV on day -6,
      cyclophosphamide IV on days -5 and -4, anti-thymocyte globulin IV on days -4 and -2, and
      total body irradiation on days -3 to 0. Patients also receive methylprednisolone IV every 12
      hours for 4 doses on days -2 to 0. Tacrolimus IV is administered continuously on day -1 and
      continues either orally or IV for 6 months. Bone marrow is infused on day 0. Filgrastim
      (G-CSF) is administered subcutaneously from day 0 until blood counts recover.

        -  Arm I: Patients receive allogeneic bone marrow that has been processed to produce a
           mononuclear cell preparation.

        -  Arm II: Patients receive unprocessed allogeneic bone marrow. Patients are followed
           weekly for 100 days and then at 6 months.

      PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 17 months.
    

Intervention name(s): anti-thymocyte globulin; filgrastim; cyclophosphamide; fludarabine phosphate; methylprednisolone; tacrolimus; allogeneic bone marrow transplantation; in vitro-treated bone marrow transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Methylprednisolone; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus; Antilymphocyte Serum
Allocation: Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; adult acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; graft versus host disease; childhood myelodysplastic syndromes