NCT01522976

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

A Randomized Phase II/III Study of Azacitidine in Combination With Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination With Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 282 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase II/III trial studies how well azacitidine works with or without lenalidomide or vorinostat in treating patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Lenalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether azacitidine is more effective with or without lenalidomide or vorinostat in treating myelodysplastic syndromes or chronic myelomonocytic leukemia.

Detailed 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.

Conditions

• Chronic Myelomonocytic Leukemia
• Chronic Myelomonocytic Leukemia-1
• Chronic Myelomonocytic Leukemia-2
• Myelodysplastic Syndrome
• Myelodysplastic Syndrome With Excess Blasts
• Myelodysplastic Syndrome With Excess Blasts-1
• Myelodysplastic Syndrome/Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	Given SC or IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Lenalidomide	Given PO
DRUG	Vorinostat	Given PO

Timeline

• Start date: 2012-03-01
• Primary completion: 2015-06-01
• Completion: 2026-03-19
• First posted: 2012-02-01
• Last updated: 2026-03-31
• Results posted: 2016-03-22

Locations

294 sites across 2 countries: United States, Canada