Azacitidine Plus Phenylbutyrate in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

RATIONALE: Azacitidine plus phenylbutyrate may help leukemia cells develop into normal white blood cells. PURPOSE: Phase I trial to study the effectiveness of combining azacitidine and phenylbutyrate in treating patients who have acute myeloid leukemia or myelodysplastic syndrome.

OBJECTIVES: * Determine the safety and toxicity of azacitidine in combination with phenylbutyrate in patients with recurrent, refractory, or untreated acute myeloid leukemia or myelodysplastic syndrome. * Determine the minimal effective pharmacologic dose of azacitidine required to consistently inhibit DNA methyltransferase in this patient population. * Obtain preliminary clinical and/or laboratory data suggesting potential therapeutic activity of this combination regimen in these patients. OUTLINE: This is a dose deescalation study of azacitidine. Patients receive azacitidine subcutaneously daily on days 1-5 and 29-33 followed by phenylbutyrate IV continuously on days 5-12 and 33-40. Treatment continues for at least 2 courses in the absence of disease progression. Patients with responsive disease may receive an additional 2 months of therapy. Cohorts of 3-6 patients receive deescalating doses of azacitidine until the minimal effective pharmacologic dose (MEPD) is determined. The MEPD is defined as the dose above the dose at which more than 1 of 6 patients do not meet the target enzyme inhibition of greater than 90%. Once the MEPD and toxicity have been established for a 5 day schedule, daily dose schedule of azacitidine is increased to 10, 14, and 21 days, followed by phenylbutyrate for 7 days. Courses are repeated every 28 days. PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study within 2 years.