Randomized Phase II Study of Epigenetic Priming Using Decitabine With Induction Chemotherapy in Patients With Acute Myelogenous Leukemia (AML)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of acute myeloid leukemia (AML) as defined by the World Health Organization

- Molecular AML-risk group is less-than-favorable as defined by any of the following
criteria:

- The absence of good-risk karyotype t(8;21), inv(16), t(16;16), or t(15;17)
identified by metaphase karyotype

- The absence of t(8;21), inv(16), t(16;16), or t(15;17) identified by fluorescent
in situ hybridization (FISH)

- The absence of the corresponding fusion transcripts, AML1-ETO, CBFβ- SMMHC, or
PML-RARα, identified by reverse transcriptase-polymerase chain reaction (RT-PCR)

- Patient does not have acute promyelocytic leukemia (APL, FAB M3)

- Patients with central nervous system (CNS) (or leptomeningeal) infiltration by AML
may be considered for treatment at the Investigator's discretion and following
discussion with the Principle Investigator

PATIENT CHARACTERISTICS:

- ECOG performance status ≤ 2 (Karnofsky ≥ 60%)

- Adequate cardiac function as defined by either of the following:

- An echocardiogram demonstrating an ejection fraction within normal limits

- A MUGA scan demonstrating an ejection fraction within normal limits

- AST(SGOT)/ALT(SGPT) ≤ 2.5 times institutional upper limit of normal (ULN)

- Creatinine ≤ 2 mg/dL OR creatinine clearance ≥ 50 mL/min

- Total bilirubin ≤ 2 times ULN

- Patients with documented diagnosis of Gilbert syndrome resulting in elevated
total bilirubin levels will be eligible, provided all other eligibility criteria
are met

- Patients with a total bilirubin of 2-3 mg/dL and direct (conjugated) bilirubin
in the normal range will be eligible, provided all other eligibility criteria
are met

- No patient with circulating blast count (CBC) > 50,000/μL (subjects may be enrolled
if CBC is controlled by hydroxyurea and/or, if clinically indicated, by
leukophoresis)

- Not pregnant or nursing

- Negative pregnancy test

- Women and men of childbearing potential must use two acceptable methods of birth
control—one highly effective method (e.g., IUD, oral or non-oral hormonal
contraceptive, tubal ligation, or partner's vasectomy) and one additional effective
method (e.g., latex condom, diaphragm or cervical cap) at the same time from the time
of screening through final Treatment Response Assessment

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition of decitabine, cytarabine, or daunorubicin hydrochloride

- No uncontrolled intercurrent illness considered by the investigator to constitute an
unwarranted high risk for investigational drug treatment; examples include, but are
not limited to, the following:

- Uncontrolled serious infection

- Unstable angina pectoris

- Uncontrolled cardiac arrhythmia

- Active second malignancy requiring treatment

- Symptomatic congestive heart failure

- No HIV-positive patients with a CD4 count < 200 cells/μL

- Patients with HIV infection and a CD4 count ≥ 200 cells/μL are eligible but
combination antiretroviral therapy should be held during administration of
chemotherapy

- No patient with a psychiatric disorder, altered mental status, or social situation
that would preclude understanding of the informed consent process and/or limit
compliance with study requirements

- No patients with inability or unwillingness, in the opinion of the investigator, to
comply with the protocol requirements

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for acute myeloid leukemia (AML) other than hydroxyurea

- No chemotherapy (other than hydroxyurea) or radiation within the 2 weeks prior to
planned therapy on this study or ongoing adverse events due to agents administered
more than 2 weeks earlier

- No concurrent treatment with other investigational agents

- No cumulative lifetime dose of anthracycline chemotherapeutic > 80 mg/m^2

- No other concurrent antineoplastic medications

- No concurrent herbal medications and supplements

- No concurrent erythroid-stimulating agents (e.g., erythropoietin, Aranesp)