Acute Leukemias Acute Myeloid Leukemia Acute Lymphoblastic Leukemia
Conditions
Interventions
Experimental: Bleximenib
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 St
Sponsors
Shirahase Toru
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1: - Age 2 years and above (pediatric cohort only), all other cohorts 18 years and above - Relapsed or refractory (R/R) acute leukemia and has exhausted, or is ineligible for, available therapeutic options - 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 (=) 30 milliliter per minute (mL/min) per four variable MDRD equation.For pediatric participants an estimated or measured glomerular filtration rate >40 mL/min per the CKiD (Chronic Kidney Disease in Children) Schwartz formula - Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Pediatric participants only: Performance status >=70 by Lansky scale (for participants less than [=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
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 halflives of the agent (whichever is shorter)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability 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. [Time Frame: Up to 4 years and 9 months] Phase 1: Number of Participants with AEs by Severity 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. [Time Frame: Up to 4 years and 9 months] Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT) Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5. [Time Frame: Up to 28 days Cycle 1] Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh) Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment. [Time Frame: Up to 4 years and 9 months] | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1 and 2: Plasma Concentration of Bleximenib Plasma concentration of bleximenib will be reported. [Time Frame: Up to 4 years and 9 months] Phase 1 and 2: Overall Response Rate (ORR) ORR is defined as the percentage of participants who achieve any response. [Time Frame: Up to 4 years and 9 months] Phase 1: Duration of Response (DOR) DOR will be calculated among responders from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first. [Time Frame: Up to 4 years and 9 months] Phase 1 and 2: Time To Response (TTR) TTR is defined for the responders as the time from the date of the first dose of bleximenib to the date of the first documented response. [Time Frame: Up to 4 years and 9 months] Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh) The duration of CR/CRh is defined from the date of first CR or CRh response achieved to the date of first evidence of relapsed disease or death due to any cause, whichever occurs first, for participants who achieve a CR or CRh. [Time Frame: Up to 4 years and 9 months] Phase 2: Time To CR/CRh Time to CR/CRh is defined for responders as the time from the date of the first dose of bleximenib to the date of first achieving either CR or CRh, depending on which milestone is reached. [Time Frame: Up to 4 years and 9 months] Phase 2: Event-free survival (EFS) EFS is defined as the time from the date of first dose of study treatment to the date of treatment failure, relapse, or death due to any cause, whichever occurs first. [Time Frame: Up to 4 years and 9 months] Phase 2: Overall survival (OS) OS is defined from the date of first dose of study treatment to the date of death due to any cause. [Time Frame: Up to 4 years and 9 months] Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi MRD-nega | — |
Countries
Australia, Brazil, Canada, China, France, Israel, Japan, Republic of Korea, Spain, Taiwan Province of China, United Kingdom of Great Britain, United States of America
Contacts
Public ContactMedical Information Center
Janssen Pharmaceutical K.K.
Outcome results
None listed