NCT03268954

Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)

A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 454 (actual)
• Sponsor: Takeda · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine. (An event is defined as death or transformation to AML in participants with MDS or CMML, whichever occurs first, and is defined as death in participants with low-blast AML).

Detailed description

The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment with azacitidine. This study will look at the overall survival, event-free survival and response to treatment in people who take pevonedistat and azacitidine when compared to people who take single-agent azacitidine. The study will enroll approximately 450 participants. Once enrolled, participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups in 28-day treatment cycles: * Pevonedistat 20 mg/m\^2 and azacitidine 75 mg/m\^2 combination * Single-agent azacitidine 75 mg/m\^2 All participants will receive azacitidine via intravenous or subcutaneous route. Participants randomized to the combination arm will also receive pevonedistat intravenous infusion. This multi-center trial will be conducted Spain, Belgium, Brazil, Canada, Czech Republic, France, Germany, Israel, Italy, the United States, Australia, Greece, Japan, Mexico, Poland, Russia, Korea, Turkey, China and United Kingdom. The overall time to participate in this study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days after the last dose of study drug or before the start of subsequent anti-neoplastic therapy if that occurs sooner. Participants with HR MDS or CMML will have EFS follow-up study visits every month if their disease has not transformed to AML and they have not started subsequent therapy. Participants with low-blast AML will have response follow-up study visits every month until they relapse from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted every 3 months) when they have confirmed transformation to AML (for participants with HR MDS or CMML at enrollment) or experienced PD (for participants with low-blast AML at study enrollment).

Conditions

• Myelodysplastic Syndrome
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	Azacitidine	Azacitidine intravenous or subcutaneous formulation.
DRUG	Pevonedistat	Pevonedistat intravenous infusion.

Timeline

• Start date: 2017-11-28
• Primary completion: 2021-05-28
• Completion: 2024-10-14
• First posted: 2017-08-31
• Last updated: 2025-10-29
• Results posted: 2022-09-22

Locations

242 sites across 20 countries: United States, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Israel, Italy, Japan, Mexico, Poland, Russia, South Korea, Spain, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study