A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Leukemias; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia

Treatments: Drug: Bleximenib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04811560

2023-506581-31-00 (Registry Identifier)

CR108998

75276617ALE1001 (Other Identifier)

2020-005967-30 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D[s]) of bleximenib in phase 1 (Part 1 [Dose Escalation] and to determine the safety and tolerability at RP2D in Phase 1 Part 2 (Dose expansion). The purpose of the Phase 2 part of the study is to evaluate the efficacy of bleximenib at the RP2D.

Enrollment: 400 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Phase 1:

• Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options
• Participants greater than or equal (>=)12 and less than (<) 18 years of age with a body weight of >= 40 kg are only eligible for the Phase 1 adolescent cohort
• Acute leukemia harboring histone-lysine N-methyltransferase 2A (KMT2A), nucleophosmin 1 gene (NPM1) or nucleoporin 98 gene or nucleoporin 214 gene (NUP98 or NUP214) alterations

Phase: 2

• Participants greater than 18 years are eligible
• Must have had an initial diagnosis of acute myeloid leukemia (AML) per the WHO 2022 classification criteria.
• AML harboring KMT2A-r (gene rearrangement/translocation) or NPM1 mutations only

For Both Phase 1 and 2:

• Pretreatment clinical laboratory values meeting the following criteria: (a) Hematology: white blood cell (WBC) count less than or equal to (<=) 20*10^9/liter (L) and renal function; Estimated or measured glomerular filtration rate greater than or equal to (>=) 50 milliliter per minute (mL/min) per four variable modified diet in renal disease (MDRD) equation
• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent participants only: Performance status >=70 by Lansky scale (for participants less than [<]16 years of age) or >=70 Karnofsky scale (for participants >=16 years of age)
• A participant of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin at screening and within 48 hours prior to the first dose of study treatment
• A participant must agree to all the following during the study and for 90 days after the last dose of study treatment: (a) wear a condom when engaging in any activity that allows for passage of ejaculate to another person; (b) not to donate sperm or freeze for future use for the purpose of reproduction. In addition, the participant should be advised of the benefit for a partner to use a highly effective method of contraception as condom may break or leak

Exclusion criteria

• Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to World Health Organization (WHO) 2016 criteria
• Active central nervous system (CNS) disease
• Prior solid organ transplantation
• QTc according to Fridericia's formula (QTcF) for males >= 450 millisecond (msec) or for females >= 470 msec. Participants with a family history of Long QT syndrome are excluded
• Exclusion criteria related to stem cell transplant: a. Received prior treatment with allogenic bone marrow or stem cell transplant <=3 months before the first dose of study treatment; b. Has evidence of graft versus host disease; c. Received donor lymphocyte infusion <=1 month before the first dose of study treatment; d. Requires immunosuppressant therapy (exception: daily doses <=10 milligrams (mg) prednisone or equivalent are allowed for adrenal replacement)
• Prior cancer immunotherapy within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment. Additional prior cancer therapies must not be given within 4 weeks prior to enrollment or 5 half-lives of the agent (whichever is shorter)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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400 participants in 1 patient group

Bleximenib

Experimental group

Description:

Participants in Phase 1 Part 1 (dose escalation) will receive bleximenib orally. The dose levels will be escalated based on the dose limiting toxicities (DLT) evaluation by Study Evaluation Team (SET) until the recommended Phase 2 Doses (RP2Ds) have been identified. Participants in Phase 1 Part 2 (dose expansion) will receive bleximenib orally at the RP2D(s) determined in Part 1. Food effect cohort (optional) participants will receive bleximenib orally on Cycle 2 Day 1 under fasted condition and on Cycle 2 Day 2 under fed condition. Participants in Phase 2 part of the study will receive bleximenib orally at the RP2D level(s).

Treatment:

Drug: Bleximenib