Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)

Acute Myeloid Leukemia Clinical Trial

Official title: A Measurable Residual Disease (MRD) Driven, Phase II Study of Venetoclax Plus Chemotherapy for Newly Diagnosed Younger Patients With Intermediate Risk Acute Myeloid Leukemia: A Tier 1 MYELOMATCH Clinical Trial

Status Not yet recruiting

Clinical Trial Summary

This phase II MyeloMATCH treatment trial compares cytarabine with daunorubicin versus cytarabine with daunorubicin and venetoclax versus venetoclax with azacitidine for the treatment of younger patients with intermediate risk acute myeloid leukemia (AML). Cytarabine is a drug that inhibits some of the enzymes needed for deoxyribonucleic acid (DNA) replication and repair and can slow or stop the growth of cancer cells. Daunorubicin is a drug that blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. 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. Azacitidine is a drug that interacts with DNA to activate tumor-suppressing genes, resulting in an anti-tumor effect. Adding venetoclax to cytarabine and daunorubicin, and adding venetoclax to azacitidine, may work better than the usual treatment of cytarabine with daunorubicin alone. To decide if they are better, the study doctors are looking to see if venetoclax increases the rate of elimination of AML in participants by 20% or more compared to the usual approach.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To compare the rates of undetectable measurable residual disease (MRD) in patients who achieve a complete remission/complete remission with incomplete count recovery (CR/CRi) after induction therapy with 7 +3 (cytarabine + daunorubicin hydrochloride [daunorubicin]) versus (vs.) azacitidine + venetoclax vs. 7+3 + venetoclax.

SECONDARY OBJECTIVES:

I. To estimate the frequency and severity of toxicities with each of the regimens.

II. To estimate complete remission (CR) rates (with and without MRD), complete remission with incomplete count recovery (CRi) (with and without MRD) rates, event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) with each of the regimens.

TERTIARY OBJECTIVES:

I. To evaluate response to therapy received according to genomic findings. II. To evaluate MRD kinetics by following patients with detectable MRD through Tier 2 and beyond.

III. To evaluate longer term outcomes by treatment arm, genomics, MRD outcome, and other features as patients receive additional myeloMATCH therapies to generate testable hypotheses for more precise patient selection for these therapies.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive daunorubicin intravenously (IV), cytarabine IV, and venetoclax orally (PO) on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.

ARM II: Patients receive azacitidine IV or subcutaneously (SC) and venetoclax PO on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated.

ARM III: Patients receive daunorubicin IV and cytarabine IV on study and undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

• NCT number: NCT05554393
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 30, 2024
• Completion date: December 31, 2025