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Combining Enasidenib with Standard Treatment for Higher-Risk Myelodysplastic Syndrome

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

Phase 2 Interventional National Cancer Institute (NCI) · NCT06577441

This study is testing if adding a new drug called enasidenib to standard treatment can help people with higher-risk myelodysplastic syndrome and an IDH2 mutation achieve better remission rates.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment54 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Locations140 sites (Berkeley, California and 139 other locations)
Trial IDNCT06577441 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of adding enasidenib to the standard treatment of cedazuridine-decitabine in patients with higher-risk myelodysplastic syndrome (MDS) who have an IDH2 mutation. The study aims to compare the complete remission rates between the combination therapy and the standard treatment alone. Secondary objectives include assessing event-free survival, overall survival, toxicity levels, and the rate of measurable residual disease. The trial involves various interventions, including biospecimen collection and bone marrow assessments.

Who should consider this trial

Good fit: Ideal candidates are patients diagnosed with higher-risk myelodysplastic syndrome who have an IDH2 mutation and have not received prior anti-cancer therapy.

Not a fit: Patients currently receiving cytarabine-containing therapy or those who have had prior anti-cancer treatments for MDS or AML may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve remission rates and overall survival for patients with higher-risk IDH2-mutated MDS.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating myelodysplastic syndromes, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* GENERAL MYLEOMATCH REGISTRATION CRITERIA:

  * Patients must be registered to the Master Screening and Reassessment Protocol (MSRP) and assigned to this protocol by the MATCHBox Treatment Verification Team.
  * Participants must not have received prior anti-cancer therapy for AML or MDS.

    * Note: Hydroxyurea to control the white blood cell count (WBC) is allowed.
    * Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility.
  * Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide is allowed
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients must have a morphologically-confirmed diagnosis of MDS with a Revised International Prognostic Scoring System (IPSS-R) score ≥ 4.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients must have a detectable pathogenic IDH2 mutation based on the National Cancer Institute (NCI) Myeloid Panel.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): No prior treatment with deoxyribonucleic acid (DNA) methyltransferase inhibitors (ASTX727, azacitidine, or decitabine).
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Prior treatment with growth factors (ESA, granulocyte colony-stimulating factor \[g-CSF\], thrombopoietin \[TPO\] agonist), lenalidomide or luspatercept is allowed with a maximum limit of 1 month of exposure.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with therapy-related MDS are allowed.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Age ≥ 18 years.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

  * Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome, if the total bilirubin is ≤ 3.0 x ULN, then they are eligible for enrollment.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) ≤ 3.0 x upper limit of normal (ULN).
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Creatinine clearance ≥ 30 mL/min

  * To be calculated using Cockroft Gault formula.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects.

  * Therefore, for women of childbearing potential only, a negative pregnancy test done as part of screening lab work prior to registration is required.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* REGISTRATION ELIGIBILITY CRITERIA (STEP 1): Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Patients on the ASTX727 monotherapy arm (Regimen 1) that do not achieve a CR (complete response), CRL (CR with limited count recovery), or CRh (CR with partial count recovery) after completing 6 cycles of study treatment.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): ECOG performance status ≤ 2.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Total bilirubin ≤ 1.5 x upper limit of normal (ULN).

  * Unless elevated due to Gilbert's syndrome. In patients with Gilbert's syndrome if the total bilirubin is ≤ 3.0 x ULN, then they are eligible for enrollment.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): AST (SGOT)/ALT (SGPT) ≤ 3.0 x upper limit of normal (ULN)
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Creatinine clearance ≥ 30 mL/min

  * To be calculated using Cockroft Gault formula.
* RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2): Not pregnant and not nursing, because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects.

Where this trial is running

Berkeley, California and 139 other locations

+90 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Myelodysplastic Syndrome
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.