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A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Leukemia,Myeloid,Acute
Date of first enrollment	09/09/2025
Target sample size	600
Countries of recruitment	Australia,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,Denmark,Japan,France,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Korea Republic Of,Japan,Mexico,Japan,Poland,Japan,Portugal,Japan,Spain,Japan,Taiwan Province Of China,Japan,Turkiye,Japan,United Kingdom Of Great Britain,Japan,United States Of America,Japan
Study type	Interventional
Intervention(s)	Experimental: Arm A: Bleximenib and Venetoclax (VEN) + Azacitidine (AZA) Participants with acute myeloid leukemia (AML) will receive bleximenib in combination with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycles and treatment will continue until progression or unacceptable toxicity. Drug: Bleximenib Bleximenib will be administered orally. Other Names: JNJ-75276617 Drug: Venetoclax (VEN) VEN will be administered orally. Drug: Azacitidine (AZA) AZA will be administered intravenously or subcutaneously. Placebo Comparator: Arm B: Placebo and Venetoclax (VEN) + Azacitidine (AZA) Participants with AML will receive placebo in combination with VEN and AZA for 28-days treatment cycles, and treatment will continue until progression or unacceptable toxicity. Drug: Venetoclax (VEN) VEN will be administered orally. Drug: Azacitidine (AZA) AZA will be administered intravenously or subcutaneously. Drug: Placebo Placebo will be administered orally.

Outcome(s)

Primary Outcome

1. Percentage of Participants who Achieve Complete Remission (CR) [Time Frame: Up to 4 years and 1 month] 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). 2. Overall Survival (OS) [Time Frame: Up to 4 years and 1 month] Overall survival time is defined as the time duration from the date of randomization to death due to any cause.

Secondary Outcome

3. Event-free survival (EFS) [Time Frame: Up to 4 years and 1 month]EFS is defined as the time from randomization to treatment failure, relapse, or death due to any cause, whichever occurs first. 4. Duration of CR [Time Frame: Up to 4 years and 1 month]Duration of CR will be estimated among responders from the date of initial documentation of CR, to the date of first documented evidence of relapse, or death due to any cause, whichever occurs first, respectively. 5. Time to CR [Time Frame: Up to 4 years and 1 month]Time to CR is defined as time from randomization to first documented response. 6. Rate of CR Without Measurable Residual Disease (MRD-) [Time Frame: Up to 4 years and 1 month] Rate of CR MRD- is defined as percentage of participants who have achieved CR without MRD. 7. Percentage of Participants who Achieved Transfusion Independence [Time Frame: Up to 4 years and 1 month]Transfusion independence is defined as lack of requirement for red blood cell (RBC) and platelet transfusions during any 56-day period. 8. Percentage of Participants with Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT) [Time Frame: Up to 4 years and 1 month]Allo-HSCT rate is defined as the percentage of participants who have undergone allo-HSCT after randomization. 9. Number of Participants with Adverse Events (AEs) [Time Frame: Up to 4 years and 1 month]An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life threatening and Grade 5= Death related to adverse event. 10. Number of Participants with Abnormalities in Clinical Laboratory Parameters [Time Frame: Up to 4 years and 1 month]Participants with abnormalities in clinical laboratory parameters will be reported. 11. Serum Concentration of Bleximenib [Time Frame: Up to 4 years and 1 month]Serum samples will be analyzed to determine concentrations of bleximenib.

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include 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
Exclude 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