Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia
Condition: Leukemia
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the
      growth of cancer cells. It also helps stop the patient's immune system from rejecting the
      transplanted stem cells. When the healthy stem cells are infused into the patient they may
      help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
      platelets. If the patient's stem cells are to be transplanted, the patient is also treated
      with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells
      or deliver cancer-killing substances to them without harming normal cells. It is not yet
      known whether combination chemotherapy is more effective with or without gemtuzumab
      ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

      PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab
      ozogamicin, and stem cell transplant to see how well they work compared to combination
      chemotherapy and peripheral stem cell transplant alone in treating patients with acute
      myeloid leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  To compare the overall survival (OS) between two induction regimens (standard versus
           dose intense daunorubicin and cytarabine) in patients with de novo AML.

        -  To compare disease-free survival (DFS) between two consolidation regimens.

        -  To compare overall survival between two consolidation regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      induction therapy (standard-dose daunorubicin vs high-dose daunorubicin).

        -  Induction therapy: Patients are randomized to 1 of 2 induction arms.

             -  Standard: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days
                1-3 and cytarabine IV continuously on days 1-7.

             -  High dose: Patients receive high-dose daunorubicin IV over 10-15 minutes on days
                1-3 and cytarabine as in arm I.

      Patients in both arms may receive a second course of induction therapy if complete remission
      (CR) is not achieved after the first course. The second course is administered as in arm I to
      all patients. Patients who don't achieve CR after 2 courses of induction therapy are removed
      from study.

      Patients who achieve CR after induction therapy proceed to post-remission therapy with EITHER
      allogeneic transplantation only (on or off study) OR consolidation therapy and autologous
      transplantation (on study), according to risk status and donor status.

      Patients who are considered at intermediate or high risk for relapse (unfavorable
      cytogenetics/high WBC) and have a suitable related donor undergo an allogeneic
      transplantation. Patients with intermediate-risk cytogenetics, WBC no greater than
      100,000/mm^3, and appropriate donors have the option of undergoing allogeneic
      transplantation.

        -  Allogeneic transplantation: Within 1-3 months after recovery from induction therapy,
           patients receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over
           4 hours on days -3 and -2. Allogeneic bone marrow or peripheral blood stem cells (PBSCs)
           are infused on day 0. Patients receive graft-vs-host disease (GVHD) prophylaxis
           comprising cyclosporine IV over 1-4 hours beginning on day -1 and then orally (when
           tolerated) twice daily until day 180. Alternatively, patients may receive tacrolimus IV
           over 24 hours beginning on day -1 and then orally twice daily until day 180. Patients
           also receive methotrexate IV on days 1, 3, 6, and 11.

      Patients who do not meet the criteria for allogeneic transplantation (i.e., are favorable
      risk or do not have a matching related donor) or who opt not to undergo allogeneic
      transplantation proceed to consolidation therapy followed by randomization to 1 of 2
      autologous transplantation arms.

        -  Consolidation therapy: Beginning 2-8 weeks after recovery from induction therapy,
           patients receive high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and
           5. A second course is administered 3 weeks after blood recovery. Patients receive
           filgrastim (G-CSF) subcutaneously (SC) daily for 4 days and then autologous PBSCs are
           harvested by leukapheresis.

        -  Autologous stem cell transplantation: Patients are randomized to 1 of 2 autologous
           transplantation arms.

             -  Arm I: Within 1 month after PBSC collection, patients receive conditioning
                comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over
                2 hours on days -3 and -2. Patients then undergo autologous PBSC transplantation on
                day 0. Patients receive sargramostim (GM-CSF) or G-CSF IV or SC beginning on day 0
                and continuing until blood counts recover.

             -  Arm II (closed to accrual as of 10/4/2007): Within 2-4 weeks after PBSC collection,
                patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV
                beginning on day 10 and continuing until blood counts recover. Within 2-3 weeks
                after blood count recovery, patients receive conditioning and undergo autologous
                PBSC transplantation as in arm I.

      Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months
      for up to 7 years.

      ACTUAL ACCRUAL: A total of 657 patients were accrued for this study.
    

Intervention name(s): sargramostim; busulfan; cyclophosphamide; cytarabine; gemtuzumab ozogamicin (GO); Daunorubicin; Autologous HCT; Allogeneic HCT
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention description(s): Given IV or as an injection; Given IV; Given IV; Given as a continuous infusion; Given IV; Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.; Autologous hematopoietic cell transplantation; Allogeneic hematopoietic cell transplantation
Other intervention name(s): Leukine; Myleran; Endoxan; Cytoxan; Neosar; Procytox; Revimmune; cytophosphane; cytosine arabinoside; Mylotarg; daunomycin; daunomycin cerubidine; Autologous hematopoietic cell transplantation; Allogeneic hematopoietic cell transplantation
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Busulfan; Daunorubicin; Gemtuzumab; Sargramostim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: acute myeloid leukemia; autologous transplantation; gemtuzumab ozogamicin