A Study of Bleximenib, Venetoclax and Azacitidine For Treatment of Participants With Acute Myeloid Leukemia (AML) (cAMeLot-2)

Janssen (J&J Innovative Medicine)

Status and phase: Not yet enrolling; Phase 3

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: Venetoclax (VEN); Drug: Azacitidine (AZA); Drug: Bleximenib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06852222

75276617AML3001 (Other Identifier)

2024-520154-38-00 (Registry Identifier)

Details and patient eligibility

About

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).

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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600 participants in 2 patient groups, including a placebo group

Arm A: Bleximenib and Venetoclax (VEN) + Azacitidine (AZA)

Experimental group

Description:

Participants with acute myeloid leukemia (AML) will receive bleximenib in combination with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycle and treatment will continue until progression or unacceptable toxicity.

Treatment:

Drug: Bleximenib

Drug: Azacitidine (AZA)

Drug: Venetoclax (VEN)

Arm B: Placebo and Venetoclax (VEN) + Azacitidine (AZA)

Placebo Comparator group

Description:

Participants with AML will receive placebo in combination with VEN and AZA for 28-days treatment cycle, and treatment will continue until progression or unacceptable toxicity.

Treatment:

Drug: Placebo

Drug: Bleximenib

Drug: Azacitidine (AZA)

Drug: Venetoclax (VEN)