Chemotherapy With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill
      them or deliver cancer-killing substances to them without harming normal cells. It is not yet
      known if combining combination chemotherapy with monoclonal antibody therapy will kill more
      cancer cells.

      PURPOSE: Randomized phase III trial to determine the effectiveness of combination
      chemotherapy with or without gemtuzumab ozogamicin in treating patients who have acute
      myeloid leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the antileukemic activity of standard induction chemotherapy with or without
           gemtuzumab ozogamicin in elderly patients with previously untreated acute myeloid
           leukemia.

        -  Determine the overall survival of patients treated with these regimens.

        -  Determine the rate of response, disease-free survival, event-free survival, incidence of
           relapse, and incidence of death of patients treated with these regimens.

        -  Determine the rate, type, and grade of toxicity of these regimens in these patients.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to age (61-69 vs 70-75), CD33 positivity (less than 5% vs 5-19% vs 20-80% vs more
      than 80% vs unknown), initial WBC before hydroxyurea administration if needed (less than
      30,000/mm^3 vs at least 30,000/mm^3), and participating center. Patients are randomized to 1
      of 2 treatment arms.

        -  Arm I:

             -  Induction (phase I): Patients receive gemtuzumab ozogamicin IV over 2 hours on days
                1 and 15.

             -  Induction (phase II/MICE regimen): Beginning between days 50 and 53, patients
                receive mitoxantrone IV over 30 minutes on days 1, 3, and 5; etoposide IV over 1
                hour on days 1-3; and cytarabine IV continuously on days 1-7. Bone marrow
                evaluation is performed on day 29. Patients with partial remission (PR) receive a
                second course of MICE chemotherapy regimen. Patients with complete remission (CR)
                after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients
                with progressive disease go off therapy.

             -  Consolidation: Beginning within 4 weeks of documentation of CR, patients receive
                gemtuzumab ozogamicin IV over 2 hours on day 0; idarubicin IV on days 1, 3, and 5;
                etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-5.
                After at least day 30, patients receive a second consolidation course in the
                absence of disease progression or unacceptable toxicity.

        -  Arm II:

             -  Induction (MICE regimen): Patients receive mitoxantrone, etoposide, and cytarabine
                as in arm I induction. Bone marrow evaluation is performed on day 29. Patients with
                PR receive a second course of MICE chemotherapy regimen. Patients with CR after 1
                or 2 courses of MICE regimen proceed to consolidation therapy. Patients with
                progressive disease go off therapy.

             -  Consolidation: Patients receive idarubicin, etoposide, and cytarabine as in arm I
                consolidation.

      Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months
      thereafter.

      PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this
      study within 3.75 years.
    

Intervention name(s): cytarabine; etoposide; gemtuzumab ozogamicin; idarubicin; mitoxantrone hydrochloride
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Cytarabine; Etoposide; Mitoxantrone; Idarubicin; Gemtuzumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute monocytic leukemia (M5b); adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); untreated adult acute myeloid leukemia; secondary acute myeloid leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22)