NCT06672146|RecruitingPhase 2FDA Drug

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

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2024-08951MM1OA-S03U10CA180888

Study Type

interventional

Target

Locations

2 countries

Sites

131

Timeline

RegisteredNov 2024

StartedMay 2025

CompletionMar 2027

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

10mo left

Started May 2025

Geographic Reach

2 countries

131 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

1.9 years study duration

Study Progress58%

May 2025Mar 2027

First Submitted

Initial submission to the registry

November 1, 2024

Completed

3 days until next milestone

First Posted

Study publicly available on registry

November 4, 2024

Completed

6 months until next milestone

Study Start

First participant enrolled

May 16, 2025

Completed

1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2027

Last Updated

June 11, 2026

Status Verified

February 1, 2026

Enrollment Period

1.9 years

First QC Date

November 1, 2024

Last Update Submit

June 10, 2026

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

Minimal residual disease negative (MRDneg) complete remission (CR) rate
A randomized design will be used to compare binary endpoints in two arms with a single interim futility analysis. For the final analysis, a 2-sample proportion z-test will be used to compare the MRDneg-CR rates between arms with a two-sided alpha of 20%.
Baseline to 5 years

Secondary Outcomes (4)

Relapse-free survival (RFS)
Baseline to 5 years
Event-free survival
Baseline to 5 years
Duration of response
Baseline to 5 years
OS
Baseline to 5 years

Study Arms (2)

Arm 1 (ASTX727 + venetoclax)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyDrug: Decitabine and CedazuridineDrug: Venetoclax

Arm 2 (ASTX727 + venetoclax + enasidenib)

EXPERIMENTAL

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.

Procedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyDrug: Decitabine and CedazuridineDrug: EnasidenibDrug: Venetoclax

Interventions

EnasidenibDRUG

Given PO

Also known as: AG 221, AG-221, AG221, CC-90007 Free Base

Arm 2 (ASTX727 + venetoclax + enasidenib)

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection