Vorinostat and Decitabine in Treating Patients With Relapsed, Refractory, or Poor-Prognosis Hematologic Cancer or Other Diseases

PRIMARY OBJECTIVES: I. To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLT) of vorinostat in combination with Decitabine in patients with relapsed/refractory or poor prognosis acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS) or chronic myeloid leukemia in accelerated or blastic phase (CML-BP). 1.2 To describe the clinical activity of the combination of Decitabine and vorinostat in this patient population. 1.3 To determine the in vivo molecular effects of this combination. This will include measuring the effects on DNA methylation, histone H3 and H4 acetylation and changes in gene expression. 1.4 To determine the pharmacokinetic characteristics of the combination. OUTLINE: This is a dose-escalation study. Patients receive decitabine IV over 1 hour on days 1-5 and oral vorinostat (SAHA) three times daily on days 6-19. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of decitabine and SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at that dose. After completion of study treatment, patients are followed for 4 weeks.