NCT03238248

Pevonedistat and Azacitidine in MDS or MDS/MPN Patients Who Fail Primary Therapy With DNA Methyl Transferase Inhibitors

A Phase II Trial of Pevonedistat and Azacitidine in MDS or MDS/MPN Patients Who Fail Primary Therapy With DNA Methyl Transferase Inhibitors

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 71 (actual)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the treatment combination of pevonedistat and azacitidine in the setting of DNA methyltransferase inhibitor(s) failure in patients with relapsed/refractory myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative neoplasm.

Detailed description

Primary Objective: To compare survival of patients treated with a combination of pevonedistat and azacitidine after failure of DNA methyltransferase inhibitors (DNMTi) to historical survival for patients with relapsed/refractory myelodysplastic syndrome (MDS) or myelodysplastic/ myeloproliferative overlap syndromes (MDS/MPN) who are ineligible for hematopoietic stem cell transplant (HSCT) Secondary Objectives: * To determine the rate of hematologic improvement (HI) in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure * To determine the complete remission (CR) and marrow CR rates in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure * To determine the reduction of bone marrow blasts in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure Exploratory Objectives: * To correlate the mutation burden in patients with relapsed/refractory MDS or MDS/MPN with response to treatment with pevonedistat and azacitidine * To correlate genomic aberrations with rate of response and survival in relapsed/refractory MDS or MDS/MPN patients treated with pevonedistat and azacitidine * To measure the effect of pevonedistat treatment in combination with azacitidine on quality of life in patients with relapsed/refractory MDS or MDS/MPN * To define epigenetic biomarkers for pevonedistat use in relapsed/refractory MDS or MDS/MPN

Conditions

• Myelodysplastic Syndromes
• Myeloproliferative Neoplasm

Interventions

Type	Name	Description
DRUG	Azacitidine Subcutaneous Injection or Intravenous Infusion	75 mg/m2
DRUG	Pevonedistat Infusion	20 mg/m2
PROCEDURE	Bone Marrow Biopsy & Aspirate	Removal of a small piece of bone and bone marrow by inserting a needle into hip bone.

Timeline

• Start date: 2017-08-07
• Primary completion: 2022-09-30
• Completion: 2023-11-27
• First posted: 2017-08-03
• Last updated: 2024-11-04
• Results posted: 2023-11-21

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study