NCT06672146

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 93 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

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

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Decitabine and Cedazuridine	Given PO
DRUG	Enasidenib	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2025-05-16
• Primary completion: 2027-03-31
• Completion: 2027-03-31
• First posted: 2024-11-04
• Last updated: 2026-04-17

Locations

114 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study