RecruitingInterventionalPhase 3

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2A Rearrangements or NPM1 Mutations Who Are Ineligible for Intensive Chemotherapy

NCT ID: NCT06852222Sponsor: Janssen Research & Development, LLCLast updated: 2026-06-05

Summary

The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine (AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants with newly diagnosed Acute Myeloid Leukemia (AML) with a mutation in the NPM1 or KMT2A gene.

Arms & interventions

DrugBleximenib
Bleximenib will be administered orally.
DrugVenetoclax (VEN)
VEN will be administered orally.
DrugAzacitidine (AZA)
AZA will be administered intravenously or subcutaneously.
DrugPlacebo
Placebo will be administered orally.

Outcome measures

Primary

Percentage of Participants who Achieve Complete Remission (CR)
CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0 \* 10\^9/Liter (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL).
Time frame: Up to 4 years and 1 month
Overall Survival (OS)
Overall survival time is defined as the time duration from the date of randomization to death due to any cause.
Time frame: Up to 4 years and 1 month

Secondary

Event-free survival (EFS)
Time frame: Up to 4 years and 1 month
Duration of CR
Time frame: Up to 4 years and 1 month
Time to CR
Time frame: Up to 4 years and 1 month
Rate of CR Without Measurable Residual Disease (MRD-)
Time frame: Up to 4 years and 1 month
Percentage of Participants who Achieved Transfusion Independence
Time frame: Up to 4 years and 1 month
Percentage of Participants with Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)
Time frame: Up to 4 years and 1 month
Number of Participants with Adverse Events (AEs)
Time frame: Up to 4 years and 1 month
Number of Participants with Abnormalities in Clinical Laboratory Parameters
Time frame: Up to 4 years and 1 month
Serum Concentration of Bleximenib
Time frame: Up to 4 years and 1 month

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion criteria: * Be 18 years of age or older at the time of informed consent * Previously untreated lysine N-methyltransferase 2A gene rearranged (KMT2Ar) or nucleophosmin 1 gene mutated (NPM1m) acute myeloid leukemia (AML) with greater than or equal to (\> or =) 10% bone marrow blasts per 2022 international Consensus Classification criteria * Ineligible for intensive chemotherapy based on the following criteria: a) \>= 75 years of age and ineligible per physician's discretion, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, b) \>=18 to \<75 years of age with \>= 1 of the following comorbidities: i) ECOG performance status of 2, ii) Severe cardiac disorder, iii) Severe pulmonary disorder, iv) Renal impairment, v) Moderate hepatic impairment vi) Comorbidity that, in the investigator's opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented before enrollment as defined in the protocol. Ineligibility for intensive chemotherapy should be explicitly approved by a multidisciplinary team in countries in which this process is standard of care * Participants must have adequate hepatic and renal function * A female participant must agree not to be pregnant, breast-feed, plan to become pregnant and use protocol-specified contraception while enrolled in this study and for 6 months after the last dose of study treatment * A male participant must agree to use protocol-specified contraception while enrolled in this study for at least 90 days after the last dose of study treatment * Must sign an informed consent form indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study Exclusion criteria: * Diagnosis of acute promyelocytic leukemia (APL) * Known active leukemic involvement of the central nervous system (CNS) * Recipient of solid organ transplant * Any cardiac disorders such as heart attack, uncontrolled/unstable chest pain, congestive heart failure, uncontrolled or symptomatic irregular heartbeat, blockage of a blood vessel to brain, or transient ischemic (decreased oxygen in tissue) attack within 6 months of randomization * Active infectious hepatitis * Live, attenuated vaccine within 4 weeks of randomization * Known allergies, hypersensitivity, or intolerance of bleximenib, azacitidine, or venetoclax excipients

Study locations (50)

University of Alabama at Birmingham

Birmingham, Alabama, 35294

Recruiting

Cancer Treatment Center of America Phoenix

Goodyear, Arizona, 85338

Recruiting

The University of Arizona Cancer Center

Tucson, Arizona, 85724

Recruiting

University of Arkansas at Little Rock

Little Rock, Arkansas, 72204

Recruiting

City of Hope

Duarte, California, 91010

Recruiting

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012

Recruiting

Medical Oncology Hematology Consultants, PA

Newark, Delaware, 19713

Recruiting

Florida Cancer Specialists & Research Institute

Fort Myers, Florida, 33901

Recruiting

Jupiter Research

Jupiter, Florida, 33458

Recruiting

Orlando Health Cancer Institute

Orlando, Florida, 32806

Recruiting

Moffit Cancer center

Tampa, Florida, 33612

Recruiting

Cleveland Clinic Florida

Weston, Florida, 33331

Recruiting

University of Chicago Medicine

Chicago, Illinois, 60637

Recruiting

Illinois Cancer Specialists

Niles, Illinois, 60714

Recruiting

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536

Recruiting

UofL Health Brown Cancer Center

Louisville, Kentucky, 40202

Recruiting

Norton Cancer Institute

Louisville, Kentucky, 40207

Recruiting

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02115

Recruiting

Henry Ford Health System

Detroit, Michigan, 48202

Recruiting

Trinity Health Michigan Heart - Ann Arbor Campus

Ypsilanti, Michigan, 48106

Recruiting

Washington University in St Louis

St Louis, Missouri, 63130

Recruiting

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756

Recruiting

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601

Recruiting

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263

Recruiting

New York Presbyterian - Weill Cornell

New York, New York, 10065

Recruiting

University of Rochester Medical Center

Rochester, New York, 14642

Recruiting

Einstein-Montefiore Medical Center

The Bronx, New York, 10467

Recruiting

Atrium Health

Charlotte, North Carolina, 28204

Recruiting

Novant Health Charlotte

Charlotte, North Carolina, 28204

Recruiting

Carolina Oncology Specialists

Charlotte, North Carolina, 28207

Recruiting

Novant Health Winston Salem

Winston-Salem, North Carolina, 27106

Recruiting

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157

Recruiting

Gabrail Cancer Center

Canton, Ohio, 44718

Recruiting

Oncology Hematology Care

Cincinnati, Ohio, 45226

Recruiting

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting

Cleveland Clinic

Cleveland, Ohio, 44195

Recruiting

Providence Portland Medical Center

Portland, Oregon, 97213

Recruiting

Providence Oncology and Hematology Care Clinic Westside

Portland, Oregon, 97225

Recruiting

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

Recruiting

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

Recruiting

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15260

Recruiting

University of Tennessee

Knoxville, Tennessee, 37920

Recruiting

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232

Recruiting

Baylor University Medical Center

Dallas, Texas, 75246

Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

Texas Oncology - Northeast

Tyler, Texas, 75702

Recruiting

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, 23298

Recruiting

Swedish Cancer Institute

Seattle, Washington, 98104

Recruiting

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

Recruiting