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

Recruiting now · Phase 2

Conditions studied: Acute Myeloid Leukemia

In brief

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.

Key facts

Study ID

NCT06672146

Run by

National Cancer Institute (NCI)

People needed

93

Starts

2025-05-16

Expected to finish

2027-03-31

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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, or with an AML defining genetic abnormality as described by the World Health Organization (WHO) classification of AML, 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, myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) with the exception of hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, colony-stimulating factors, erythropoiesis-stimulating agents, thrombopoietin receptor agonist, lenalidomide, luspatercept, immunosuppressive therapy, intrathecal chemotherapy, cytarabine (up to 1 g/m\^2 for the purpose of cytoreduction for hyperleukocytosis/trial eligibility), and/or leukapheresis, with a maximum limit of 1 month of exposure.
• Note: White blood cell (WBC) must be < 25 x 10\^9/L prior to start of treatment. Hydroxyurea, leukapheresis, and cytarabine ≤ 1g/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 with central nervous system (CNS) involvement are eligible if follow-up CNS evaluation shows no evidence of progression, or if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
• 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. 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

Where it is running

• Banner University Medical Center - Tucson — Tucson, Arizona, United States (enrolling)
• Northwestern Medicine Glenview Outpatient Center — Glenview, Illinois, United States (enrolling)
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States (enrolling)
• UCSF Medical Center-Parnassus — San Francisco, California, United States (enrolling)
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (enrolling)
• Memorial Regional Hospital/Joe DiMaggio Children's Hospital — Hollywood, Florida, United States (enrolling)
• Miami Cancer Institute — Miami, Florida, United States (enrolling)
• Memorial Hospital West — Pembroke Pines, Florida, United States (enrolling)
• Augusta University Medical Center — Augusta, Georgia, United States (enrolling)
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States (enrolling)
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States (enrolling)
• Saint Alphonsus Cancer Care Center-Nampa — Nampa, Idaho, United States (enrolling)
• Saint Luke's Cancer Institute - Nampa — Nampa, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Post Falls — Post Falls, Idaho, United States (enrolling)
• Kootenai Clinic Cancer Services - Sandpoint — Sandpoint, Idaho, United States (enrolling)
• Northwestern University — Chicago, Illinois, United States (enrolling)
• University of Illinois — Chicago, Illinois, United States (enrolling)
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (enrolling)
• Northwestern Medicine Cancer Center Kishwaukee — DeKalb, Illinois, United States (enrolling)
• NorthShore University HealthSystem-Evanston Hospital — Evanston, Illinois, United States (enrolling)
• Northwestern Medicine Cancer Center Delnor — Geneva, Illinois, United States (enrolling)
• NorthShore University HealthSystem-Glenbrook Hospital — Glenview, Illinois, United States (enrolling)
• Northwestern Medicine Grayslake Outpatient Center — Grayslake, Illinois, United States (enrolling)

Full record on ClinicalTrials.gov

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