Comparison of Three Treatment Regimens in Treating Patients With Relapsed or Refractory Acute Myelogenous Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Monoclonal antibodies such as gemtuzumab ozogamicin can locate
      cancer cells and either kill them or deliver cancer-killing substances to them without
      harming normal cells. Combining more than one drug or combining monoclonal antibody with
      chemotherapy may kill more cancer cells. It is not yet known which treatment regimen is more
      effective for acute myelogenous leukemia.

      PURPOSE: Randomized phase II trial to compare the effectiveness of three treatment regimens
      in treating patients who have relapsed or refractory acute myelogenous leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the rates of complete response (CR) and CR without full platelet recovery in
           patients with relapsed or refractory acute myelogenous leukemia treated with gemtuzumab
           ozogamicin and cytarabine vs daunorubicin liposomal and cytarabine vs cyclophosphamide,
           cytarabine, and topotecan.

        -  Compare the toxicities of these 3 regimens in these patients.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified by disease status
      (relapse less than 6 months after first complete response (CR) vs relapse 6-12 months after
      first CR vs refractory to conventional initial induction chemotherapy (no more than 2
      courses) or first reinduction (no more than 1 course) vs second or greater relapse).

        -  Induction: Patients are randomized to 1 of 3 treatment arms:

             -  Arm I: Patients receive cytarabine IV over 2 hours on days 1-4 and gemtuzumab
                ozogamicin IV over 2 hours on day 5.

             -  Arm II: Patients receive daunorubicin liposomal IV over a minimum of 2 hours on
                days 1-3 and cytarabine IV over 2 hours (beginning immediately after completion of
                daunorubicin liposomal infusion) on days 1-4.

             -  Arm III: Patients receive cyclophosphamide IV over 1 hour every 12 hours on days
                1-3, cytarabine IV over 2 hours (beginning immediately after completion of
                cyclophosphamide infusion) on days 2-6, and topotecan IV continuously on days 2-6.

        -  Consolidation: Patients who achieve complete remission (CR) receive 1 additional course
           of induction therapy on the same arm to which they were originally randomized beginning
           within 4-6 weeks after initial documentation of CR. Patients on arm II receive no
           additional daunorubicin liposomal if resting ejection fraction is less than 50%
           preconsolidation. All patients receive sargramostim (GM-CSF) IV over 4 hours or SQ daily
           beginning 24 hours after completion of consolidation therapy and continuing until blood
           counts recover.

      Patients are followed every 3 months through year 2, every 6 months through year 5, and then
      annually thereafter until death.

      PROJECTED ACCRUAL: A maximum of 150-165 patients (50-55 per arm) will be accrued for this
      study within 2 years.
    

Intervention name(s): sargramostim; cyclophosphamide; cytarabine; gemtuzumab ozogamicin; liposomal daunorubicin citrate; topotecan hydrochloride
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Daunorubicin; Topotecan; Gemtuzumab; Sargramostim
Allocation: Randomized
Primary purpose: Treatment
Keywords: recurrent adult acute myeloid leukemia; adult acute erythroid leukemia (M6); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute promyelocytic leukemia (M3); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute megakaryoblastic leukemia (M7); adult acute monocytic leukemia (M5b); adult acute minimally differentiated myeloid leukemia (M0)