Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Description

PRIMARY OBJECTIVES:

I. To select based on response rate (complete remission, partial remission, or hematologic improvement) either the combination of lenalidomide and azacitidine or the combination of vorinostat and azacitidine for further testing against single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase II) II. To compare overall survival between the combination arm selected in the Phase II portion of the trial to single-agent azacitidine among patients with higher-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). (Phase III)

SECONDARY OBJECTIVES:

I. To estimate relapse-free survival, overall survival and cytogenetic response rate of patients treated on each regimen.

II. To estimate the frequency and severity of toxicities of the three regimens in this patient population.

III. To investigate in a preliminary manner the frequency of subgroups from prestudy cytogenetic studies and correlate these subgroups with clinical outcomes in this patient population.

IV. To collect specimens for banking for use in future research studies.

TERTIARY OBJECTIVES:

I. To evaluate the prevalence of a pre-specified list of molecular lesions (48 total lesions).

II. To assess associations of these lesions with outcomes (response, event-free survival, relapse-free survival, and overall survival).

III. To develop a deoxyribonucleic acid (DNA) methylation biomarker predictive of response to DMTi treatment in MDS.

IV. To harness gene expression profiles as clinical biomarkers of primary resistance to DMTi in MDS.

OUTLINE: Patients are randomized to 1 of 3 treatment arms. In Phase III, patients are randomized to 1 of 2 treatment arms (the combination arm selected in Phase II or the single-agent azacitidine arm).

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, treatment repeats 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.