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)
NCT ID: NCT06577441
Last Updated: 2025-11-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
54 participants
INTERVENTIONAL
2025-06-12
2027-03-01
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Biospecimen Collection
Undergo buccal swab and blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Decitabine and Cedazuridine
Given PO
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.
Biospecimen Collection
Undergo buccal swab and blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Decitabine and Cedazuridine
Given PO
Enasidenib
Given PO
Interventions
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Biospecimen Collection
Undergo buccal swab and blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspiration
Bone Marrow Biopsy
Undergo bone marrow biopsy
Decitabine and Cedazuridine
Given PO
Enasidenib
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion 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.
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Anand A Patel
Role: PRINCIPAL_INVESTIGATOR
Alliance for Clinical Trials in Oncology
Locations
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Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
Mills Health Center
San Mateo, California, United States
Phoebe Putney Memorial Hospital
Albany, Georgia, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, United States
Illinois CancerCare-Bloomington
Bloomington, Illinois, United States
Illinois CancerCare-Canton
Canton, Illinois, United States
Illinois CancerCare-Carthage
Carthage, Illinois, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Carle at The Riverfront
Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, United States
Illinois CancerCare-Dixon
Dixon, Illinois, United States
Crossroads Cancer Center
Effingham, Illinois, United States
Illinois CancerCare-Eureka
Eureka, Illinois, United States
Illinois CancerCare-Galesburg
Galesburg, Illinois, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, United States
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, United States
Illinois CancerCare-Macomb
Macomb, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, United States
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, United States
Northwestern Medicine Orland Park
Orland Park, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, United States
Illinois CancerCare-Pekin
Pekin, Illinois, United States
Illinois CancerCare-Peoria
Peoria, Illinois, United States
Illinois CancerCare-Peru
Peru, Illinois, United States
Illinois CancerCare-Princeton
Princeton, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Springfield Clinic
Springfield, Illinois, United States
Springfield Memorial Hospital
Springfield, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, United States
Illinois CancerCare - Washington
Washington, Illinois, United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, United States
UofL Health Medical Center Northeast
Louisville, Kentucky, United States
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, United States
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, United States
Our Lady of The Lake
Baton Rouge, Louisiana, United States
Tufts Medical Center
Boston, Massachusetts, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, United States
Cancer Hematology Centers - Flint
Flint, Michigan, United States
Genesee Hematology Oncology PC
Flint, Michigan, United States
Genesys Hurley Cancer Institute
Flint, Michigan, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, United States
Essentia Health Cancer Center
Duluth, Minnesota, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
Essentia Health Sandstone
Sandstone, Minnesota, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, United States
Parkland Health Center - Farmington
Farmington, Missouri, United States
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, United States
Missouri Baptist Medical Center
St Louis, Missouri, United States
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, United States
Community Hospital of Anaconda
Anaconda, Montana, United States
Billings Clinic Cancer Center
Billings, Montana, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, United States
Logan Health Medical Center
Kalispell, Montana, United States
Community Medical Center
Missoula, Montana, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Geisinger Medical Center
Danville, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, United States
Prisma Health Cancer Institute - Easley
Easley, South Carolina, United States
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, United States
Prisma Health Cancer Institute - Greer
Greer, South Carolina, United States
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington, United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington, United States
Swedish Medical Center-First Hill
Seattle, Washington, United States
Duluth Clinic Ashland
Ashland, Wisconsin, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States
William S Middleton VA Medical Center
Madison, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Centro Comprensivo de Cancer de UPR
San Juan, , Puerto Rico
San Juan City Hospital
San Juan, , Puerto Rico
Countries
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Facility Contacts
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Other Identifiers
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NCI-2024-07049
Identifier Type: REGISTRY
Identifier Source: secondary_id
MM1MDS-A01
Identifier Type: OTHER
Identifier Source: secondary_id
MM1MDS-A01
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2024-07049
Identifier Type: -
Identifier Source: org_study_id