Maintenance Azacitidine in Elderly Patients With Acute Myeloid Leukemia (AML) in CR After Induction Chemotherapy

• Rate of Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  The secondary efficacy variable will be overall survival measured as time to death, which is the time from remission until death from any cause.
• Number of Participants with Adverse Events [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  Safety and tolerability of treatment as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0

The purpose of this study is to find out if patients older than 60, with acute myeloid leukemia, who are in complete remission following initial chemotherapy, will live longer and have a lower rate of leukemia relapse when treated with azacitidine.

Patient activity will encompass approximately 48 months: an approximate 24 month enrollment period, followed by 6 to 12 months of patient treatment. Patients will be followed for 1 year following completion of study drug treatment. During follow-up, bone marrow biopsies to confirm disease status should be obtained if peripheral blood blasts are present or if there is development of unexpected blood abnormalities to warrant suspicion of relapse, or at a minimum of every 6 months.

• Experimental: Arm I: Azacitidine Treatment
  Azacitidine 50mg/m^2 subcutaneously (injection under the skin) day 1-5, 8-9 every 4 weeks, 6-12 cycles
  Intervention: Drug: Azacitidine
• Experimental: Arm II: Azacitidine Treatment
  Azacitidine 50mg/m^2 subcutaneously day 1-5, every 4 weeks, 6-12 cycles
  Intervention: Drug: Azacitidine
• Experimental: Arm III:
  Azacitidine 50mg/m^2 subcutaneously day 1-5, 8-12 every 4 weeks, 6-12 cycles
  Intervention: Drug: Azacitidine

Inclusion Criteria:

• Histologic or cytologic confirmation of AML with greater than 20% blasts in bone marrow. All AML subtypes of the World Health Organization (WHO) classification will be included with the exception of promyelocytic leukemia and cytogenetics showing the (15;17) translocation or AML secondary to chemotherapy.
• Achieved first morphologic complete remission (CR) or first morphologic complete remission with incomplete platelet recovery (CRp) after completion of induction chemotherapy using a standard induction regimen. Up to 2 induction cycles will be allowed. Confirmation of CR is defined as < 5% blasts in the bone marrow specimen, with a count of at least 100-200 nucleated cells and absence of Auer rods, along with peripheral blood neutrophil count >1.0 x 10^9/L and platelet count >100 x 10^9/L. Confirmation of CRp is defined as <5% blasts in the bone marrow specimen, with a count of at least 100-200 nucleated cells and absence of Auer rods, with incomplete platelet recovery (ANC ≥ 1000/µL and platelets 50-99,000/µL, along with transfusion-independence of red blood cells).
• Received up to 2 cycles of any consolidation chemotherapy
• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Normal organ function at the time of screening: Total bilirubin ≤1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN; Serum creatinine ≤1.5 x ULN or creatinine clearance >60 mL/min for patients with creatinine levels above ULN
• Men must agree to avoid fathering a child throughout the study.
• Be capable of giving informed consent and have signed the informed consent form (ICF)

Exclusion Criteria:

• Greater than 12 weeks since initiation of most recent cycle of consolidation chemotherapy
• Women of childbearing potential
• Prior relapse after complete remission for AML
• AML secondary to previous exposure to cytotoxic chemotherapy known to induce leukemia
• Active malignancy other than AML
• Any diagnosis of metastatic disease
• Have hepatic tumors
• Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions other than AML <4 weeks prior to Day 1 or have not recovered from adverse events due to agents administered >4 weeks earlier
• Known leukemic involvement of the central nervous system
• Known or suspected hypersensitivity to azacitidine or mannitol
• Prior or active disease that, in the opinion of the Investigator, may interfere with the procedures or evaluations to be conducted in the study (uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements)
• Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C
• Treatment with other investigational drugs within the 30 days prior to Day 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period
• Any prior treatment with azacitidine or decitabine