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)

May 26, 2026 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Recruiting
        • Centro Comprensivo de Cancer de UPR
        • Principal Investigator:
          • Luis J. Santos Reyes
        • Contact:
      • San Juan, Puerto Rico, 00936
        • Recruiting
        • San Juan City Hospital
        • Principal Investigator:
          • Luis J. Santos Reyes
        • Contact:
          • Site Public Contact
          • Phone Number: 787-763-1296
  • United States
    • California
      • Berkeley, California, United States, 94704
        • Suspended
        • Alta Bates Summit Medical Center-Herrick Campus
      • Irvine, California, United States, 92612
        • Recruiting
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
        • Principal Investigator:
          • Deepa Jeyakumar
        • Contact:
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
        • Principal Investigator:
          • Deepa Jeyakumar
        • Contact:
      • San Mateo, California, United States, 94401
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • UF Health Cancer Institute - Gainesville
        • Contact:
          • Site Public Contact
          • Phone Number: 352-273-8010
        • Principal Investigator:
          • Dina G. Khalaf
      • Miami, Florida, United States, 33176
        • Recruiting
        • Miami Cancer Institute
        • Principal Investigator:
          • Firas El Chaer
        • Contact:
          • Site Public Contact
          • Phone Number: 786-596-2000
      • Pembroke Pines, Florida, United States, 33028
        • Recruiting
        • Memorial Hospital West
        • Contact:
          • Site Public Contact
          • Phone Number: 954-265-4325
        • Principal Investigator:
          • Fernando M. Vargas Madueno
    • Georgia
      • Albany, Georgia, United States, 31701
        • Recruiting
        • Phoebe Putney Memorial Hospital
        • Principal Investigator:
          • Vamsi Kota
        • Contact:
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • Saint Luke's Cancer Institute - Boise
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Coeur d'Alene, Idaho, United States, 83814
        • Recruiting
        • Kootenai Health - Coeur d'Alene
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Fruitland, Idaho, United States, 83619
        • Recruiting
        • Saint Luke's Cancer Institute - Fruitland
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Meridian, Idaho, United States, 83642
        • Recruiting
        • Saint Luke's Cancer Institute - Meridian
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Nampa, Idaho, United States, 83687
        • Recruiting
        • Saint Luke's Cancer Institute - Nampa
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Nampa, Idaho, United States, 83687
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Nampa
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Post Falls, Idaho, United States, 83854
        • Recruiting
        • Kootenai Clinic Cancer Services - Post Falls
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Sandpoint, Idaho, United States, 83864
        • Recruiting
        • Kootenai Clinic Cancer Services - Sandpoint
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • Illinois
      • Bloomington, Illinois, United States, 61704
        • Recruiting
        • Illinois CancerCare-Bloomington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Canton, Illinois, United States, 61520
        • Recruiting
        • Illinois CancerCare-Canton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Carthage, Illinois, United States, 62321
        • Recruiting
        • Illinois CancerCare-Carthage
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Anand A. Patel
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Yasmin Abaza
      • Chicago, Illinois, United States, 60625
        • Recruiting
        • Swedish Covenant Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 773-878-8200
        • Principal Investigator:
          • Robert M. Eisner
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Contact:
        • Principal Investigator:
          • Yasmin Abaza
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Dixon, Illinois, United States, 61021
        • Recruiting
        • Illinois CancerCare-Dixon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 815-285-7800
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Eureka, Illinois, United States, 61530
        • Recruiting
        • Illinois CancerCare-Eureka
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Evanston, Illinois, United States, 60201
        • Recruiting
        • NorthShore University HealthSystem-Evanston Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 847-570-2109
        • Principal Investigator:
          • Robert M. Eisner
      • Galesburg, Illinois, United States, 61401
        • Recruiting
        • Illinois CancerCare-Galesburg
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Contact:
        • Principal Investigator:
          • Yasmin Abaza
      • Glenview, Illinois, United States, 60026
        • Recruiting
        • NorthShore University HealthSystem-Glenbrook Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 847-570-2109
        • Principal Investigator:
          • Robert M. Eisner
      • Glenview, Illinois, United States, 60026
        • Recruiting
        • Northwestern Medicine Glenview Outpatient Center
        • Principal Investigator:
          • Yasmin Abaza
        • Contact:
          • Site Public Contact
          • Phone Number: 312-695-1102
      • Grayslake, Illinois, United States, 60030
        • Recruiting
        • Northwestern Medicine Grayslake Outpatient Center
        • Principal Investigator:
          • Yasmin Abaza
        • Contact:
          • Site Public Contact
          • Phone Number: 312-695-1102
      • Highland Park, Illinois, United States, 60035
        • Recruiting
        • NorthShore University HealthSystem-Highland Park Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 847-570-2109
        • Principal Investigator:
          • Robert M. Eisner
      • Kewanee, Illinois, United States, 61443
        • Recruiting
        • Illinois CancerCare-Kewanee Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Lake Forest, Illinois, United States, 60045
        • Recruiting
        • Northwestern Medicine Lake Forest Hospital
        • Contact:
        • Principal Investigator:
          • Yasmin Abaza
      • Macomb, Illinois, United States, 61455
        • Recruiting
        • Illinois CancerCare-Macomb
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • Maywood, Illinois, United States, 60153
        • Recruiting
        • Loyola University Medical Center
        • Principal Investigator:
          • Stephanie B. Tsai
        • Contact:
          • Site Public Contact
          • Phone Number: 708-226-4357
      • New Lenox, Illinois, United States, 60451
        • Recruiting
        • UC Comprehensive Cancer Center at Silver Cross
        • Contact:
        • Principal Investigator:
          • Anand A. Patel
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • HSHS Saint Elizabeth's Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Orland Park, Illinois, United States, 60462
        • Recruiting
        • University of Chicago Medicine-Orland Park
        • Contact:
        • Principal Investigator:
          • Anand A. Patel
      • Orland Park, Illinois, United States, 60462
      • Ottawa, Illinois, United States, 61350
        • Recruiting
        • Illinois CancerCare-Ottawa Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Pekin, Illinois, United States, 61554
        • Recruiting
        • Illinois CancerCare-Pekin
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peoria, Illinois, United States, 61615
        • Recruiting
        • Illinois CancerCare-Peoria
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peru, Illinois, United States, 61354
        • Recruiting
        • Illinois CancerCare-Peru
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Princeton, Illinois, United States, 61356
        • Recruiting
        • Illinois CancerCare-Princeton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 800-444-7541
      • Springfield, Illinois, United States, 62781
        • Recruiting
        • Springfield Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Vamsi K. Vasireddy
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Contact:
        • Principal Investigator:
          • Yasmin Abaza
      • Washington, Illinois, United States, 61571
        • Recruiting
        • Illinois CancerCare - Washington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
    • Indiana
      • Crown Point, Indiana, United States, 46307
        • Recruiting
        • UChicago Medicine Northwest Indiana
        • Contact:
        • Principal Investigator:
          • Anand A. Patel
    • Iowa
      • Ankeny, Iowa, United States, 50023
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Ankeny Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Clive, Iowa, United States, 50325
        • Recruiting
        • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • Mercy Medical Center - Des Moines
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Richard L. Deming
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Iowa Methodist Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-6727
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Des Moines Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Laurel Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
        • Principal Investigator:
          • Prajwal Dhakal
      • Pella, Iowa, United States, 50219
        • Recruiting
        • UI Healthcare Mission Cancer and Blood - Pella
        • Principal Investigator:
          • Seema Harichand-Herdt
        • Contact:
      • Waukee, Iowa, United States, 50263
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Waukee Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • The James Graham Brown Cancer Center at University of Louisville
        • Principal Investigator:
          • Mohamed M. Hegazi
        • Contact:
          • Site Public Contact
          • Phone Number: 502-562-3429
      • Louisville, Kentucky, United States, 40245
        • Recruiting
        • UofL Health Medical Center Northeast
        • Principal Investigator:
          • Mohamed M. Hegazi
        • Contact:
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70805
        • Recruiting
        • LSU Health Baton Rouge-North Clinic
        • Contact:
        • Principal Investigator:
          • Harry G. Sequeira Gross
      • Baton Rouge, Louisiana, United States, 70808
        • Recruiting
        • Our Lady of The Lake
        • Contact:
          • Site Public Contact
          • Phone Number: 225-765-7659
        • Principal Investigator:
          • Harry G. Sequeira Gross
      • Baton Rouge, Louisiana, United States, 70808
        • Recruiting
        • Our Lady of the Lake Physician Group
        • Contact:
        • Principal Investigator:
          • Harry G. Sequeira Gross
    • Maryland
      • Bethesda, Maryland, United States, 20889-5600
        • Recruiting
        • Walter Reed National Military Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 301-319-2100
        • Principal Investigator:
          • Ryan Jones
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
    • Michigan
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Suspended
        • Genesee Hematology Oncology PC
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Cancer Hematology Centers - Flint
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Pontiac, Michigan, United States, 48341
        • Recruiting
        • Trinity Health Saint Joseph Mercy Oakland Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
    • Minnesota
      • Brainerd, Minnesota, United States, 56401
        • Recruiting
        • Essentia Health Saint Joseph's Medical Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Deer River, Minnesota, United States, 56636
        • Recruiting
        • Essentia Health - Deer River Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Duluth, Minnesota, United States, 55805
        • Recruiting
        • Essentia Health Cancer Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Hibbing, Minnesota, United States, 55746
        • Recruiting
        • Essentia Health Hibbing Clinic
        • Principal Investigator:
          • Bret E. Friday
        • Contact:
          • Site Public Contact
          • Phone Number: 218-786-3308
      • Minneapolis, Minnesota, United States, 55415
        • Recruiting
        • Hennepin County Medical Center
        • Contact:
        • Principal Investigator:
          • Daniel M. Anderson
      • Sandstone, Minnesota, United States, 55072
        • Recruiting
        • Essentia Health Sandstone
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Virginia, Minnesota, United States, 55792
        • Recruiting
        • Essentia Health Virginia Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
    • Missouri
      • Farmington, Missouri, United States, 63640
        • Recruiting
        • Parkland Health Center - Farmington
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sainte Genevieve, Missouri, United States, 63670
        • Recruiting
        • Sainte Genevieve County Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • St Louis, Missouri, United States, 63131
        • Recruiting
        • Missouri Baptist Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sullivan, Missouri, United States, 63080
        • Recruiting
        • Missouri Baptist Sullivan Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sunset Hills, Missouri, United States, 63127
        • Recruiting
        • BJC Outpatient Center at Sunset Hills
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
    • Montana
      • Anaconda, Montana, United States, 59711
        • Recruiting
        • Community Hospital of Anaconda
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Billings, Montana, United States, 59101
        • Recruiting
        • Billings Clinic Cancer Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Bozeman, Montana, United States, 59715
        • Recruiting
        • Bozeman Health Deaconess Hospital
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Great Falls, Montana, United States, 59405
        • Recruiting
        • Benefis Sletten Cancer Institute
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Kalispell, Montana, United States, 59901
        • Recruiting
        • Logan Health Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Missoula, Montana, United States, 59804
        • Recruiting
        • Community Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • New Jersey
      • Livingston, New Jersey, United States, 07039
        • Recruiting
        • Saint Barnabas Medical Center
        • Principal Investigator:
          • Neil D. Palmisiano
        • Contact:
      • Long Branch, New Jersey, United States, 07740
        • Recruiting
        • Monmouth Medical Center
        • Principal Investigator:
          • Neil D. Palmisiano
        • Contact:
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Principal Investigator:
          • Neil D. Palmisiano
        • Contact:
          • Site Public Contact
          • Phone Number: 732-235-7356
      • Toms River, New Jersey, United States, 08755
        • Recruiting
        • Community Medical Center
        • Principal Investigator:
          • Neil D. Palmisiano
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Recruiting
        • University of New Mexico Cancer Center
        • Contact:
        • Principal Investigator:
          • Charles Foucar
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Principal Investigator:
          • Eunice S. Wang
        • Contact:
      • Stony Brook, New York, United States, 11794
        • Recruiting
        • Stony Brook University Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-862-2215
        • Principal Investigator:
          • Suhu Liu
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Harry P. Erba
        • Contact:
          • Site Public Contact
          • Phone Number: 888-275-3853
      • Greenville, North Carolina, United States, 27834
        • Recruiting
        • East Carolina University
        • Principal Investigator:
          • Darla K. Liles
        • Contact:
    • North Dakota
      • Fargo, North Dakota, United States, 58103
        • Recruiting
        • Essentia Health Cancer Center-South University Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Jayanshu Jain
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Zimu Gong
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Medical Center
        • Contact:
        • Principal Investigator:
          • Joseph J. Vadakara
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Cancer Institute (UPCI)
        • Contact:
          • Site Public Contact
          • Phone Number: 412-647-8073
        • Principal Investigator:
          • Annie P. Im
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Recruiting
        • Geisinger Wyoming Valley/Henry Cancer Center
        • Contact:
        • Principal Investigator:
          • Joseph J. Vadakara
    • South Carolina
      • Boiling Springs, South Carolina, United States, 29316
        • Recruiting
        • Prisma Health Cancer Institute - Spartanburg
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Easley, South Carolina, United States, 29640
        • Recruiting
        • Prisma Health Cancer Institute - Easley
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Cancer Institute - Faris
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Cancer Institute - Butternut
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greenville, South Carolina, United States, 29615
        • Recruiting
        • Prisma Health Cancer Institute - Eastside
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Greer, South Carolina, United States, 29650
        • Recruiting
        • Prisma Health Cancer Institute - Greer
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
      • Seneca, South Carolina, United States, 29672
        • Recruiting
        • Prisma Health Cancer Institute - Seneca
        • Principal Investigator:
          • Suzanne R. Fanning
        • Contact:
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • University of Tennessee - Knoxville
        • Contact:
          • Site Public Contact
          • Phone Number: 865-544-9773
        • Principal Investigator:
          • Clark Cutrer
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Paul J. Shami
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • VCU Massey Comprehensive Cancer Center
        • Principal Investigator:
          • Keri R. Maher
        • Contact:
    • Washington
      • Edmonds, Washington, United States, 98026
        • Recruiting
        • Swedish Cancer Institute-Edmonds
        • Principal Investigator:
          • Charles W. Drescher
        • Contact:
      • Issaquah, Washington, United States, 98029
        • Recruiting
        • Swedish Cancer Institute-Issaquah
        • Principal Investigator:
          • Charles W. Drescher
        • Contact:
      • Seattle, Washington, United States, 98122
        • Recruiting
        • Swedish Medical Center-First Hill
        • Principal Investigator:
          • Charles W. Drescher
        • Contact:
    • Wisconsin
      • Ashland, Wisconsin, United States, 54806
        • Recruiting
        • Duluth Clinic Ashland
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Green Bay, Wisconsin, United States, 54301
        • Recruiting
        • Saint Vincent Hospital Cancer Center Green Bay
        • Principal Investigator:
          • Anthony J. Jaslowski
        • Contact:
      • Green Bay, Wisconsin, United States, 54303
        • Recruiting
        • Saint Vincent Hospital Cancer Center at Saint Mary's
        • Principal Investigator:
          • Anthony J. Jaslowski
        • Contact:
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Gundersen Lutheran Medical Center
        • Contact:
        • Principal Investigator:
          • Michael O. Ojelabi
      • Madison, Wisconsin, United States, 53705
        • Recruiting
        • William S Middleton VA Medical Center
        • Principal Investigator:
          • Christopher D. Fletcher
        • Contact:
          • Site Public Contact
          • Phone Number: 17007 608-256-1901
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-3666
        • Principal Investigator:
          • Guru Subramanian Guru Murthy
      • Stevens Point, Wisconsin, United States, 54482
      • Weston, Wisconsin, United States, 54476

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Regimen 1 (ASTX727)
Patients receive ASTX727 PO 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 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.
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration
Drug: Decitabine and Cedazuridine
Given PO
Other Names:
  • ASTX727
  • CDA Inhibitor E7727/Decitabine Combination Agent ASTX727
  • Cedazuridine/Decitabine Combination Agent ASTX727
  • Cedazuridine/Decitabine Tablet
  • Inqovi
  • C-DEC
  • DEC-C
  • ASTX 727
  • ASTX-727
  • Inaqovi
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Procedure: Biospecimen Collection
Undergo buccal swab and blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Experimental: Regimen 2 (ASTX727, enasidenib)
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.
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration
Drug: Decitabine and Cedazuridine
Given PO
Other Names:
  • ASTX727
  • CDA Inhibitor E7727/Decitabine Combination Agent ASTX727
  • Cedazuridine/Decitabine Combination Agent ASTX727
  • Cedazuridine/Decitabine Tablet
  • Inqovi
  • C-DEC
  • DEC-C
  • ASTX 727
  • ASTX-727
  • Inaqovi
Drug: Enasidenib
Given PO
Other Names:
  • AG-221
  • CC-90007 Free Base
  • AG 221
  • AG221
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Procedure: Biospecimen Collection
Undergo buccal swab and blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate
Time Frame: Up to 4 cycles of treatment
Will be assessed using the International Working Group 2023 (IWG2023) criteria. Will compare the CR rate between the two treatment arms to determine if patients treated with enasidenib + ASTX727 have a statistically significantly higher CR rate than patients treated with the ASTX727 monotherapy.
Up to 4 cycles of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response
Time Frame: From patient first achieves a response until either progression or death, assessed up to 5 years
Will be assessed only among patients who achieve a response (CR, CRL, or CRh). Will use the methods of Kaplan-Meier as well as Cox regression models.
From patient first achieves a response until either progression or death, assessed up to 5 years
Change in IDH2 variant allele frequency (VAF)
Time Frame: Baseline to end of cycle 4 and 6
Will report the percent change of VAF along with a 95% confidence interval.
Baseline to end of cycle 4 and 6
Allogeneic stem cell transplantation rate
Time Frame: Up to 5 years
Will report along with a 95% confidence interval for each treatment arm.
Up to 5 years
Event-free survival (EFS)
Time Frame: Time from randomization to either a failure to achieve a CR, CR with limited count recovery (CRL), or CR with partial count recovery (CRh) after four cycles of treatment, relapse, or death due to any cause, assessed up to 18 months
Sensitivity analyses will be conducted. Will use the methods of Kaplan-Meier as well as Cox regression models.
Time from randomization to either a failure to achieve a CR, CR with limited count recovery (CRL), or CR with partial count recovery (CRh) after four cycles of treatment, relapse, or death due to any cause, assessed up to 18 months
Overall survival (OS)
Time Frame: Time from randomization to death due to any cause, assessed up to 18 months
Will use the methods of Kaplan-Meier as well as Cox regression models.
Time from randomization to death due to any cause, assessed up to 18 months
Time to response
Time Frame: Time from randomization to documented response, assessed up to 5 years
Will be assessed only among patients who achieve a response (CR, CRL, or CRh). Will utilize the methods of Kaplan-Meier as well as Cox regression models.
Time from randomization to documented response, assessed up to 5 years
Incidence of adverse events
Time Frame: Up to 4 weeks after completion of study treatment
Will be determined using the Common Terminology Criteria for Adverse Events version 5 criteria. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest and will graphically assess differences in maximum grades observed for toxicities.
Up to 4 weeks after completion of study treatment
Measurable residual disease rate
Time Frame: At the end of cycle 4 and 6
Will be measured by flow cytometry and next generation sequencing. Will be compared and used to determine association with clinical outcomes such as CR, EFS, or OS.
At the end of cycle 4 and 6
Cytogenetic and molecular features
Time Frame: Up to 5 years
Cytogenetic and molecular classifications including Molecular International Prognostic Scoring System will be compared and used to determined association with clinical outcomes such as CR, EFS, and OS.
Up to 5 years
Time to transformation of myelodysplastic syndrome to acute myeloid leukemia (AML)
Time Frame: From randomization to transformation to AML or death from any causes, assessed up to 5 years
Will utilize the methods of Kaplan-Meier as well as Cox regression models.
From randomization to transformation to AML or death from any causes, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Anand A Patel, Alliance for Clinical Trials in Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2025

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

August 28, 2024

First Submitted That Met QC Criteria

August 28, 2024

First Posted (Actual)

August 29, 2024

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 26, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2024-07049 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180821 (U.S. NIH Grant/Contract)
  • MM1MDS-A01 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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