Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

• Probability of achieving CR or CRp [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  
• Survival rate [ Time Frame: 30 days after study registration ] [ Designated as safety issue: No ]
  
• Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Estimated by the method of Kaplan-Meier.
  
  
• Cytogenic response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Estimated as the proportion of patients achieving major and minor responses.
  
  

PRIMARY OBJECTIVES:

I. To test whether outcomes of patients of age 60 or older with previously untreated non-M3 acute myeloid leukemia treated with azacitidine plus gemtuzumab ozogamicin are sufficient to warrant phase III investigation.

II. To estimate the frequency and severity of toxicities of this regimen in the good- and poor-risk groups of patients.

III. To investigate in a preliminary manner the disease-free survival of patients who achieve complete remission and receive post-remission therapy on this study.

IV. To investigate in a preliminary manner the cytogenetic response rates of patients treated with this regimen.

V. To investigate in a preliminary manner the effects of cytogenetic abnormalities, promoter and global methylation changes, and multidrug resistance on overall survival and response to azacitidine plus gemtuzumab ozogamicin therapy.

OUTLINE: Patients are stratified according to risk status (good [60-69 years of age OR Zubrod performance status [PS] 0-1] vs poor [≥ 70 years of age AND Zubrod PS 2-3]).

REMISSION INDUCTION THERAPY: Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) once daily on days 1-7 and gemtuzumab ozogamicin IV over 2 hours on day 8. Patients with residual leukemia (blast count ≥ 5%) receive a second course of induction therapy beginning between days 15-29. Patients achieving complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) go on to receive consolidation therapy.

CONSOLIDATION THERAPY: Patients receive one course of azacitidine and gemtuzumab ozogamicin as in induction therapy.

MAINTENANCE THERAPY: Patients receive azacitidine IV over 10-40 minutes or subcutaneously on days 1-7. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsies for cytogenetic studies at baseline, remission, and relapse or progression. Marrow and blood samples are submitted to correlatives studies and submitted to SWOG ALL/CLL/CML Repository in Seattle, WA.

After completion of study therapy, patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.