SUSPENDED

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Randomized Phase II Trial of ASTX727 and Venetoclax Compared With ASTX727, Venetoclax, and Enasidenib for Newly Diagnosed Older Adults With IDH2 Mutant Acute Myeloid Leukemia: A MyeloMATCH Substudy

Quick Facts

Study Start:2025-05-16

Study Completion:2027-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:SUSPENDED

Study ID

NCT06672146

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Eric J Huselton

PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Study Locations (Sites)

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, 94704

United States

Mills Health Center

San Mateo, California, 94401

United States

Augusta University Medical Center

Augusta, Georgia, 30912

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 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

Northwestern University

Chicago, Illinois, 60611

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134

United States

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois, 60026

United States

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois, 60030

United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045

United States

Loyola University Medical Center

Maywood, Illinois, 60153

United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451

United States

Northwestern Medicine Orland Park

Orland Park, Illinois, 60462

United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555

United States

UChicago Medicine Northwest Indiana

Crown Point, Indiana, 46307

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

Our Lady of the Lake Physician Group

Baton Rouge, Louisiana, 70808

United States

Our Lady of The Lake

Baton Rouge, Louisiana, 70808

United States

MaineHealth Cancer Care and IV Therapy - Brunswick

Brunswick, Maine, 04011

United States

Mid Coast Hospital

Brunswick, Maine, 04011

United States

MaineHealth Maine Medical Center - Portland

Portland, Maine, 04102

United States

MaineHealth Cancer Care and IV Therapy - South Portland

South Portland, Maine, 04106

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

Henry Ford Hospital

Detroit, Michigan, 48202

United States

OSF Saint Francis Hospital and Medical Group

Escanaba, Michigan, 49829

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 IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197

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

Essentia Health Sandstone

Sandstone, Minnesota, 55072

United States

Essentia Health Virginia Clinic

Virginia, Minnesota, 55792

United States

Community Hospital of Anaconda

Anaconda, Montana, 59711

United States

Billings Clinic Cancer Center

Billings, Montana, 59101

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

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106

United States

Roswell Park Cancer Institute

Buffalo, New York, 14263

United States

University of Rochester

Rochester, New York, 14642

United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

Geisinger Medical Center

Danville, Pennsylvania, 17822

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

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

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

Saint Vincent Hospital Cancer Center at Oconto Falls

Oconto Falls, Wisconsin, 54154

United States

Saint Vincent Hospital Cancer Center at Sheboygan

Sheboygan, Wisconsin, 53081

United States

Sheboygan Physicians Group

Sheboygan, Wisconsin, 53081

United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay

Sturgeon Bay, Wisconsin, 54235-1495

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Eric J Huselton, PRINCIPAL_INVESTIGATOR, SWOG Cancer Research Network

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 Registration Dates

Study Start Date2025-05-16

Study Completion Date2027-03-31

Study Record Updates

Study Start Date2025-05-16

Study Completion Date2027-03-31

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia