Azacitidine as Maintenance Therapy in Treating Older Patients With Acute Myeloid Leukemia in Complete Remission After Chemotherapy

OBJECTIVES:

Primary

- Determine the disease-free survival of older patients with acute myeloid leukemia (AML)
in first complete remission treated with low-dose azacitidine as post-remission
therapy.

Secondary

- Determine overall survival of these patients receiving azacitidine as maintenance
therapy.

- Determine the safety and tolerability of azacitidine as maintenance therapy in these
patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1
of 3 treatment arms.

- Arm I: Patients receive azacitidine subcutaneously (SC) once daily on days 1-5 and
8-12.

- Arm II: Patients receive azacitidine SC once daily on days 1-5 and 8-9.

- Arm III: Patients receive azacitidine SC once daily on days 1-5. In all arms, treatment
repeats every 4 weeks for up to 12 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed acute myeloid leukemia (AML) with > 20%
blasts in bone marrow

- No promyelocytic leukemia with cytogenetics showing the (15;17) translocation

- No leukemia secondary to chemotherapy

- Achieved first complete remission after completion of a standard induction
chemotherapy regimen

- Received no more than 2 induction chemotherapy courses

- Confirmation of complete remission is defined as all of the following:

- Less than 5% blasts in the bone marrow specimen with > 10% cellularity and
absence of Auer rods

- Peripheral blood neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Received no more than 2 courses of any consolidation chemotherapy

- No prior relapse after complete remission for AML

- No metastatic disease

- No hepatic tumors

- No known leukemic involvement of the CNS

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 2 months

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Fertile patients must use effective contraception

- No active malignancy other than AML

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT < 2.5 times ULN

- Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min

- No known or suspected hypersensitivity to azacitidine or mannitol

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situations that would limit compliance with study
requirements

- No active HIV or hepatitis B or C infection

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- No radiation therapy, chemotherapy, or cytotoxic therapy for treatment of conditions
other than AML within the past 4 weeks

- No other investigational drugs within the past 30 days

- No prior azacitidine or decitabine

- No other concurrent cytotoxic or investigational drugs