• Overall survival in Phase III [ Designated as safety issue: No ]
  
• Rate of patients who started continuation therapy in Phase II [ Designated as safety issue: No ]
  

• Rate of complete remission (CR) or complete remission with incomplete recovery of platelet count (CRp) after induction and by the end of continuation therapy [ Designated as safety issue: No ]
  
• Overall progression-free survival [ Designated as safety issue: No ]
  
• Disease-free survival from CR/CRp [ Designated as safety issue: No ]
  
• Highest grade toxicity as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Compare the feasibility, toxicity, and antileukemic activity of two different dosing regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients with previously untreated acute myeloid leukemia who are not candidates for intensive chemotherapy. (phase II)
• Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase II vs standard supportive care, in terms of overall survival, in these patients. (phase III)

OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over), CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status (0-1 vs 2 vs 3-4), and participating center.

• Phase II: Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and 8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
  • Arm III: Patients receive standard supportive care.

• Phase III: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive the selected treatment (arm I or arm II) from phase II.
  • Arm II: Patients receive standard supportive care. Patients who receive GO treatment are followed monthly for 1 year and then every 3 months thereafter. Patients who receive standard supportive care are followed at least every 4 weeks.

PROJECTED ACCRUAL: A total of 259 patients (75 for phase II [25 per treatment arm] and 184 for phase III [92 per treatment arm]) will be accrued for this study within 2.5 years.