CLINICAL TRIAL / NCT04811560

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

Interventional
Active
NCT04811560

Eligibility Details Visit Clinicaltrials.gov

Contact Information

A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia

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.

Eligibility Details

Gender
All

Age Group
12 Years and up

Accepting Healthy Volunteers
No

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 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 and have relapsed/refractory disease - 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 (b) 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 female 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 - Participant must agree to all protocol required contraception requirements and avoid sperm or egg donations or freezing for future reproductive use while on study and for 90 days (males) or 6 months (females) after the last dose of study treatment 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)