Comparing New Treatments for People With Newly Diagnosed Acute Myeloid Leukemia That Has an IDH2 Gene Change (A MyeloMATCH Treatment Trial)

NCT ID: NCT06672146

Last Updated: 2026-01-27

Study Results

Results pending

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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Recruitment Status

SUSPENDED

Clinical Phase

PHASE2

Total Enrollment

93 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-16

Study Completion Date

2027-03-31

Brief Summary

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This phase II MyeloMATCH treatment trial studies how well ASTX727 and venetoclax plus enasidenib works compared to ASTX727 and venetoclax alone for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML) or younger patients who are considered unfit for standard treatment, and who have an abnormal change (mutation) in the IDH2 gene. This gene mutation can cause AML to grow and spread. This trial is being done to see if adding enasidenib to the usual treatment can help more patients with the IDH2 gene get rid of AML.

ASTX727 is a fixed-dose formulation of two drugs, cedazuridine and decitabine. 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. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Enasidenib works by stopping the growth and spread of tumor cells that have the IDH2 mutation. Giving ASTX727 and venetoclax plus enasidenib may work better in treating AML patients with the IDH2 mutation.

Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate the safety of decitabine and cedazuridine (ASTX727) + venetoclax + enasidenib (Arm 2) before initiating randomization.

II. To compare the rate of measurable residual disease (MRD) negative complete remission (CR) based on multiparameter flow cytometry (MFC) after two cycles of treatment in older adults (or unfit adults age 18 or older) with IDH2 mutated Acute Myeloid Leukemia (AML) who receive ASTX727, venetoclax, and enasidenib versus ASTX727 and venetoclax alone.

SECONDARY OBJECTIVES:

I. To estimate the composite remission rate (CR + complete remission with incomplete count recovery \[CRi\] + complete remission with partial hematologic recovery \[CRh\]), relapse-free survival (RFS), event-free survival (EFS), duration of response (DOR), and overall survival (OS) of participants by treatment arm.

II. To estimate IDH2 mutated variant allele frequency, flow cytometry MRD, and molecular MRD after two cycles of therapy in participants' bone marrow aspirates and blood by treatment arm.

III. To estimate remission rates (CR with and without MRD \[MFC and molecular MRD\], CRh and CRi), and to estimate the rates of hematologic improvement by treatment arm.

IV. To estimate the frequency and severity of adverse events by treatment arm. V. To evaluate the association between MFC and molecular MRD after two cycles of protocol treatment with the outcomes RFS and OS (landmarked by date of MRD measurement) by treatment arm.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive ASTX727 orally (PO) once daily (QD) on days 1-5 and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM 2: Patients receive ASTX727 PO QD on days 1-5, venetoclax PO QD on days 1-28, 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.

All patients undergo blood sample collection, bone marrow aspiration, and bone marrow biopsy throughout the trial.

After completion of study treatment, patients are followed up every month for the first year, every 2 months for the second year, every 3 months for the third year, and every 6 months until 5 years after registration or death.

Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 (ASTX727 + venetoclax)

Patients receive ASTX727 PO QD on days 1-5 and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow aspiration, and bone marrow biopsy throughout the trial.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Decitabine and Cedazuridine

Intervention Type DRUG

Given PO

Venetoclax

Intervention Type DRUG

Given PO

Arm 2 (ASTX727 + venetoclax + enasidenib)

Patients receive ASTX727 PO QD on days 1-5, venetoclax PO QD on days 1-28, 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 undergo blood sample collection, bone marrow aspiration, and bone marrow biopsy throughout the trial.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Decitabine and Cedazuridine

Intervention Type DRUG

Given PO

Enasidenib

Intervention Type DRUG

Given PO

Venetoclax

Intervention Type DRUG

Given PO

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Decitabine and Cedazuridine

Given PO

Intervention Type DRUG

Enasidenib

Given PO

Intervention Type DRUG

Venetoclax

Given PO

Intervention Type DRUG

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow Biopsy, Bone Marrow ASTX 727 ASTX-727 ASTX727 C-DEC CDA Inhibitor E7727/Decitabine Combination Agent ASTX727 Cedazuridine/Decitabine Combination Agent ASTX727 Cedazuridine/Decitabine Tablet DEC-C Inaqovi Inqovi AG 221 AG-221 AG221 CC-90007 Free Base ABT 199 ABT-0199 ABT-199 ABT199 GDC 0199 GDC-0199 GDC0199 RG7601 Venclexta Venclyxto

Eligibility Criteria

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Inclusion Criteria

* Participants must have been registered to the MYELOMATCH Master Screening and Reassessment Protocol prior to consenting to this study. Participants must have disease with a detectable IDH2 mutation based on central testing through the MYELOMATCH and be assigned to this clinical trial via MATCHBox prior to registration to this study

* Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH
* Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) defined by having ≥ 20% blasts in the bone marrow and/or peripheral blood, excluding acute promyelocytic leukemia (APL) with PML-RARA
* Participants must not be receiving or planning to receive any other investigational agents while on protocol therapy
* Participants must not have received prior therapy for AML or myelodysplastic syndrome (MDS) and/or myeloproliferative neoplasm (MPN) with the exception of hydroxyurea, all-trans retinoic acid (ATRA), colony-stimulating factors, erythropoiesis-stimulating agents, immunosuppressive therapy, intrathecal chemotherapy, a single dose of cytarabine for cytoreduction, and/or leukapheresis
* 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 are allowed. Participants may receive hydroxyurea prior to treatment assignment on this substudy for cytoreduction but must agree to discontinue hydroxyurea prior to beginning treatment on this substudy

* White blood cell (WBC) must be \< 25 x 10\^9/L. Hydroxyurea, leukapheresis, and cytarabine \< 1 g/m\^2 are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped prior to initiation of protocol therapy
* Participants must be ≥ 60 years old; OR must be ≥ 18 years old and considered not eligible for cytarabine-based induction therapy
* Participants must have Zubrod Performance Status of 0-3 as determined by a history and physical (H\&P) exam completed within 14 days prior to registration
* Participants must have a complete medical history and physical exam within 14 days prior to registration
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's syndrome. Participants with history of Gilbert's syndrome must have total bilirubin ≤ 3 x institutional ULN (within 14 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN, unless considered to be elevated due to disease involvement (within 14 days prior to registration)
* Participants must have adequate kidney function as evidenced by creatinine clearance ≥ 30mL/min (by Cockcroft Gault) within 14 days prior to registration
* Participants must not have a baseline corrected QT interval ≥ 480 msec using Fridericia correction (QTcF).

* NOTE: Since older participants are at risk for prolonged QTc and may require supportive care with agents that affect QTc, an electrocardiogram (ECG) is recommended if clinically indicated. If the QTc is prolonged, they should be treated on MYELOMATCH TAP instead of MM1OA-S03
* Participants must have adequate cardiac function in the assessment of their treating physician. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
* Participants must have agreed to have specimens submitted for translational medicine for MRD under MYELOMATCH and specimens must be submitted

* Enrollment to this treatment study requires prior enrollment into the myeloMATCH Master Protocol (MYELOMATCH). Participants enrolled in MYELOMATCH will submit bone marrow samples, peripheral blood samples, and buccal swabs to the Molecular Diagnostics Network (MDNet), the Clinical Laboratory Improvement Act (CLIA) laboratory network for myeloMATCH
* In addition to the MYELOMATCH specimens, there will be specimens obtained on treatment for this substudy. These specimens will be derived from procedures performed as part of standard assessments in the clinical care and management of AML with material being sent to the MDNet laboratories as specified. After performing the required tests on the specimens, the MDNet laboratories will send the residual material for biobanking and future research. Therefore, participants must be asked for their consent for the biobanking of specimens for future unspecified research. Participants may refuse this, but it is mandatory for sites to ask participants
* Participants must be offered the opportunity to participate in specimen banking
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric J Huselton

Role: PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Locations

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Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States

Site Status

Mills Health Center

San Mateo, California, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Site Status

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois, United States

Site Status

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois, United States

Site Status

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

Site Status

Northwestern Medicine Orland Park

Orland Park, Illinois, United States

Site Status

University of Chicago Medicine-Orland Park

Orland Park, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status

UChicago Medicine Northwest Indiana

Crown Point, Indiana, United States

Site Status

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, United States

Site Status

UofL Health Medical Center Northeast

Louisville, Kentucky, United States

Site Status

Our Lady of the Lake Physician Group

Baton Rouge, Louisiana, United States

Site Status

Our Lady of The Lake

Baton Rouge, Louisiana, United States

Site Status

MaineHealth Cancer Care and IV Therapy - Brunswick

Brunswick, Maine, United States

Site Status

Mid Coast Hospital

Brunswick, Maine, United States

Site Status

MaineHealth Maine Medical Center - Portland

Portland, Maine, United States

Site Status

MaineHealth Cancer Care and IV Therapy - South Portland

South Portland, Maine, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

OSF Saint Francis Hospital and Medical Group

Escanaba, Michigan, United States

Site Status

Cancer Hematology Centers - Flint

Flint, Michigan, United States

Site Status

Genesee Hematology Oncology PC

Flint, Michigan, United States

Site Status

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Site Status

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, United States

Site Status

Essentia Health - Deer River Clinic

Deer River, Minnesota, United States

Site Status

Essentia Health Cancer Center

Duluth, Minnesota, United States

Site Status

Essentia Health Hibbing Clinic

Hibbing, Minnesota, United States

Site Status

Essentia Health Sandstone

Sandstone, Minnesota, United States

Site Status

Essentia Health Virginia Clinic

Virginia, Minnesota, United States

Site Status

Community Hospital of Anaconda

Anaconda, Montana, United States

Site Status

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status

Logan Health Medical Center

Kalispell, Montana, United States

Site Status

Community Medical Center

Missoula, Montana, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Easley

Easley, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Greer

Greer, South Carolina, United States

Site Status

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Site Status

Swedish Cancer Institute-Edmonds

Edmonds, Washington, United States

Site Status

Swedish Cancer Institute-Issaquah

Issaquah, Washington, United States

Site Status

Swedish Medical Center-First Hill

Seattle, Washington, United States

Site Status

Duluth Clinic Ashland

Ashland, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, United States

Site Status

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Site Status

William S Middleton VA Medical Center

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Oconto Falls

Oconto Falls, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Sheboygan

Sheboygan, Wisconsin, United States

Site Status

Sheboygan Physicians Group

Sheboygan, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Sturgeon Bay

Sturgeon Bay, Wisconsin, United States

Site Status

Centro Comprensivo de Cancer de UPR

San Juan, , Puerto Rico

Site Status

San Juan City Hospital

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

Other Identifiers

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NCI-2024-08951

Identifier Type: REGISTRY

Identifier Source: secondary_id

MM1OA-S03

Identifier Type: OTHER

Identifier Source: secondary_id

MM1OA-S03

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180888

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-08951

Identifier Type: -

Identifier Source: org_study_id

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