NCT03383575

Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome

Targeted Therapy With the IDH2-Inhibitor Enasidenib (AG221) for High-Risk IDH2-Mutant Myelodysplastic Syndrome

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 63 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies the side effects and how well azacitidine and enasidenib work in treating patients with IDH2-mutant myelodysplastic syndrome. Azacitidine and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of enasidenib alone, and enasidenib in combination with azacitidine (AZA), for patients with isocitrate dehydrogenase 2 (IDH2) mutated myelodysplastic syndrome (MDS). II. To assess the efficacy of the combination of enasidenib + azacitidine in hypomethylating agent (HMA) naive subjects with IDH2-mutated MDS, and to assess the efficacy of enasidenib single-agent in subjects with IDH2-mutated MDS who are relapsed/refractory to HMA therapy. SECONDARY OBJECTIVES: I. To evaluate molecular and cellular markers that may be predictive of antitumor activity and/or resistance including evaluation of IDH2 variant allele fraction (VAF) levels during treatment and presence of co-occurring mutations. II. To assess overall survival, event-free survival and duration of response of enasidenib alone, and enasidenib in combination with azacitidine. EXPLORATORY OBJECTIVES: I. To assess changes in cellular differentiation and changes in deoxyribonucleic acid (DNA) methylation profiles in IDH2-mutated MDS treated with enasidenib alone and with enasidenib + azacitidine. II. To evaluate quality of life (QOL) using an MDS-specific measure. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients who are HMA-naive receive enasidenib orally (PO) once daily (QD) on days 1-28 and azacitidine intravenously (IV) oveer 30-60 minutes or subcutaneously (SC) on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients relapsed and/or refractory to HMA therapy receive enasidenib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Conditions

• Acute Myeloid Leukemia
• Blasts 20-30 Percent of Bone Marrow Nucleated Cells
• Chronic Myelomonocytic Leukemia
• IDH2 Gene Mutation
• Myelodysplastic Syndrome With Excess Blasts
• Recurrent High Risk Myelodysplastic Syndrome
• Refractory High Risk Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV or SC
DRUG	Enasidenib	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies

Timeline

• Start date: 2018-01-17
• Primary completion: 2027-02-28
• Completion: 2027-02-28
• First posted: 2017-12-26
• Last updated: 2026-02-17

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study