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
3 other identifiers
interventional
54
2 countries
140
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jun 2025
140 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 28, 2024
CompletedFirst Posted
Study publicly available on registry
August 29, 2024
CompletedStudy Start
First participant enrolled
June 12, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
June 11, 2026
April 1, 2026
1.7 years
August 28, 2024
June 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Complete response (CR) rate
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 Outcomes (10)
Event-free survival (EFS)
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 from randomization to death due to any cause, assessed up to 18 months
Time to response
Time from randomization to documented response, assessed up to 5 years
Duration of response
From patient first achieves a response until either progression or death, assessed up to 5 years
Incidence of adverse events
Up to 4 weeks after completion of study treatment
- +5 more secondary outcomes
Study Arms (2)
Regimen 1 (ASTX727)
ACTIVE COMPARATORPatients 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.
Regimen 2 (ASTX727, enasidenib)
EXPERIMENTALPatients 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.
Interventions
Undergo buccal swab and blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- 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.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (140)
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Mills Health Center
San Mateo, California, 94401, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Miami Cancer Institute
Miami, Florida, 33176, United States
Memorial Hospital West
Pembroke Pines, Florida, 33028, United States
Phoebe Putney Memorial Hospital
Albany, Georgia, 31701, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704, United States
Illinois CancerCare-Canton
Canton, Illinois, 61520, United States
Illinois CancerCare-Carthage
Carthage, Illinois, 62321, United States
Northwestern University
Chicago, Illinois, 60611, United States
Swedish Covenant Hospital
Chicago, Illinois, 60625, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Illinois CancerCare-Dixon
Dixon, Illinois, 61021, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Illinois CancerCare-Eureka
Eureka, Illinois, 61530, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035, United States
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Illinois CancerCare-Macomb
Macomb, Illinois, 61455, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Loyola University Medical Center
Maywood, Illinois, 60153, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269, United States
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350, United States
Illinois CancerCare-Pekin
Pekin, Illinois, 61554, United States
Illinois CancerCare-Peoria
Peoria, Illinois, 61615, United States
Illinois CancerCare-Peru
Peru, Illinois, 61354, United States
Illinois CancerCare-Princeton
Princeton, Illinois, 61356, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Springfield Clinic
Springfield, Illinois, 62702, United States
Springfield Memorial Hospital
Springfield, Illinois, 62781, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
Illinois CancerCare - Washington
Washington, Illinois, 61571, United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana, 46307, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325, United States
Iowa Methodist Medical Center
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
UI Healthcare Mission Cancer and Blood - Pella
Pella, Iowa, 50219, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202, United States
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245, United States
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, 70805, United States
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, 70808, United States
Our Lady of The Lake
Baton Rouge, Louisiana, 70808, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118, United States
Cancer Hematology Centers - Flint
Flint, Michigan, 48503, United States
Genesee Hematology Oncology PC
Flint, Michigan, 48503, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
Parkland Health Center - Farmington
Farmington, Missouri, 63640, United States
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080, United States
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, 63127, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Monmouth Medical Center
Long Branch, New Jersey, 07740, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Community Medical Center
Toms River, New Jersey, 08755, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
East Carolina University
Greenville, North Carolina, 27834, United States
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316, United States
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640, United States
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605, United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605, United States
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615, United States
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650, United States
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672, United States
University of Tennessee - Knoxville
Knoxville, Tennessee, 37920, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026, United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029, United States
Swedish Medical Center-First Hill
Seattle, Washington, 98122, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
William S Middleton VA Medical Center
Madison, Wisconsin, 53705, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
Centro Comprensivo de Cancer de UPR
San Juan, 00927, Puerto Rico
San Juan City Hospital
San Juan, 00936, Puerto Rico
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anand A Patel
Alliance for Clinical Trials in Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2024
First Posted
August 29, 2024
Study Start
June 12, 2025
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2027
Last Updated
June 11, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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