PRIMARY OBJECTIVES: I. To test whether the response rate (complete remission, partial remission, or hematologic improvement) of patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) who receive either the combination of lenalidomide and azacitidine or the combination of vorinostat and azacitidine is improved compared to patients who receive single-agent azacitidine. II. To estimate relapse-free survival, overall survival and cytogenetic response rate of patients treated on each regimen. III. To estimate the frequency and severity of toxicities of the three regimens in this patient population. IV. To investigate in a preliminary manner the frequency of subgroups from pre-study cytogenetic studies and correlate these subgroups with clinical outcomes in this patient population. V. To collect specimens for banking for use in future research studies. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 or days 1-5 and 8-9, and lenalidomide orally (PO) once daily (QD) on days 1-21. ARM II: Patients receive azacitidine as in arm I. ARM III: Patients receive azacitidine as in arm I and vorinostat PO twice daily (BID) on days 3-9. In all arms, courses repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 5 years.
Last updated: 04/22/2013