Clinical trial NCT06852222: A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Acute Myeloid Leukemia (AML)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2025-02-28
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 Acute Myeloid Leukemia (AML).


Eligibility criteria: 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) Comorbidity that, in the investigator's opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented and approved by the sponsor before enrollment defined in the protocol
* 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 and for 6 months 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 excipients

Primary outcomes:
measure: Percentage of Participants who Achieve Complete Remission (CR)
timeFrame: Up to 4 years and 1 month
measure: Overall Survival (OS)
timeFrame: Up to 4 years and 1 month
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: Up to 4 years and 1 month
measure: Duration of CR
timeFrame: Up to 4 years and 1 month
measure: Time to CR
timeFrame: Up to 4 years and 1 month
measure: Rate of CR-Measurable Residual Disease (MRD)
timeFrame: Up to 4 years and 1 month
measure: Percentage of Participants who Achieved Transfusion Independence
timeFrame: Up to 4 years and 1 month
measure: Percentage of Participants with Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)
timeFrame: Up to 4 years and 1 month
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 4 years and 1 month
measure: Number of Participants with Abnormalities in Clinical Laboratory Parameters
timeFrame: Up to 4 years and 1 month
measure: Serum Concentration of Bleximenib
timeFrame: Up to 4 years and 1 month
Other outcomes:
Locations:
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospita Ein Kerem
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Sapporo
country: Japan
facility: Aiiku Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center Liouying Branch
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: