NCT06577441

Testing the Addition of an IDH2 Inhibitor, Enasidenib, to Usual Treatment (Cedazuridine-Decitabine) for Higher-Risk Myelodysplastic Syndrome (MDS) With IDH2 Mutation (A MyeloMATCH Treatment Trial)

A Randomized Phase II Trial of Enasidenib-Based Therapies Versus Cedazuridine-Decitabine in Higher-Risk IDH2-Mutated Myelodysplastic Syndrome: A MyeloMATCH Sub-Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II MyeloMATCH treatment trial compares the usual treatment of cedazuridine-decitabine (ASTX727) to the combination treatment of ASTX727 and enasidenib in treating patients with higher-risk, IDH2-mutated myelodysplastic syndrome (MDS). ASTX727 is a combination of two drugs, decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Enasidenib is an enzyme inhibitor that may stop the growth of cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with enasidenib may be effective in treating patients with higher-risk IDH2-mutated MDS.

Detailed description

PRIMARY OBJECTIVE: I. To compare the complete remission (CR) rate of enasidenib + decitabine and cedazuridine (ASTX727) and ASTX727 monotherapy in patients with higher-risk IDH2-mutated MDS using International Working Group 2023 (IWG2023) response criteria. SECONDARY OBJECTIVES: I. To estimate the median event-free survival (EFS) at designated time point(s) for each treatment arm. II. To estimate the median overall survival (OS) at designated time point(s) for each treatment arm. III. To estimate the frequency and severity of toxicities with each regimen in this patient population. IV. To estimate the median time to response for each treatment arm. V. To estimate the median duration of response for each treatment arm. VI. To estimate the IDH2 variant allele frequency (VAF) reduction for each treatment arm. VII. To estimate the rate of allogeneic hematopoietic cell transplantation for each treatment arm. VIII. To compare rates of partial response (PR), CR with limited count recovery (CRL), CR with partial count recovery (CRh), and hematologic improvement (HI) using IWG 2023 response criteria between treatment arms. IX. To compare the measurable residual disease (MRD) kinetics by flow cytometry and next generation sequencing (NGS) at designated time point(s) at the end of cycle 4 \& 6 and to assess any correlation with clinical outcomes (e.g. CR, EFS, OS). X. To estimate the median time to transformation of MDS to acute myeloid leukemia (AML). EXPLORATORY OBJECTIVES: I. To estimate CR rate, median EFS, and median OS in patients treated with ASTX727 monotherapy that crossover to the treatment arm with ASTX727 + enasidenib after 6 cycles if CR is not achieved. II. To estimate CR rate, median EFS, and median OS for patients based on Molecular International Prognostic Scoring System (IPSS-M) prognostic risk score at diagnosis, stratified for score level. III. To estimate concordance between centrally-performed molecular studies and cytogenetics to those done locally. OUTLINE: Patients are randomized to 1 of 2 regimens. REGIMEN 1: Patients receive ASTX727 orally (PO) once daily (QD) on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR, CRL, or CRh at the end of cycle 6 may cross-over to Regimen 2. Patients who experience CR, PR, or stable disease (SD) any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to Tier Advancement Pathway (TAP). Patients also undergo bone marrow biopsy and aspiration throughout the study. Patients may also undergo optional buccal swab on study, and/or optional additional bone marrow aspiration and blood sample collection on study and at disease progression. REGIMEN 2: Patients receive ASTX727 PO QD on days 1-5 and enasidenib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience CR, PR, or SD any time after 4 cycles of treatment may be reassessed in order to go to a higher myeloMATCH tier assignment or to TAP. Patients also undergo bone marrow biopsy and aspiration throughout the study. Patients may also undergo optional buccal swab on study, and/or optional additional bone marrow aspiration and blood sample collection on study and at disease progression. After completion of study treatment, patients are followed up every 6 months for up to 5 years after registration.

Conditions

• Myelodysplastic Syndrome

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo buccal swab and blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Decitabine and Cedazuridine	Given PO
DRUG	Enasidenib	Given PO

Timeline

• Start date: 2025-06-12
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2024-08-29
• Last updated: 2026-04-13

Locations

139 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study