• Overall survival [ Designated as safety issue: No ]
  

• Response (complete remission [CR] or complete remission with incomplete recovery of platelet count [CRp]) rate after induction [ Designated as safety issue: No ]
  
• Disease-free survival after CR/CRp [ Designated as safety issue: No ]
  
• Incidence of relapse after CR/CRp [ Designated as safety issue: No ]
  
• Incidence of death without relapse after CR/CRp [ Designated as safety issue: No ]
  
• Event-free survival [ Designated as safety issue: No ]
  
• Toxicity (highest grade) assessed by International Working Group CTC v2.0 [ Designated as safety issue: Yes ]
  

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.