Acute Leukemias, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
Conditions
Brief summary
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.
Interventions
DRUGBleximenib
Bleximenib is administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
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 (\<=) 20\*10\^9/liter (L) and (b) renal function; For adult participants, estimated or measured glomerular filtration rate greater than equal (\>=) 30 milliliter per minute (mL/min) per four variable MDRD equation. For pediatric participants an estimated or measured glomerular filtration rate \>50 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 \[\<\]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 *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | Up to 4 years and 9 months | 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. |
| Phase 1: Number of Participants with AEs by Severity | Up to 4 years and 9 months | 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. |
| Phase 1: Part 1: Percentage of Participants with Dose-Limiting Toxicity (DLT) | Up to 28 days Cycle 1 | Percentage of participants with DLT will be assessed accordingly to national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5. |
| Phase 2: Rate of Complete Remission or Complete Remission with Partial Hematologic Recovery (CR/CRh) | Up to 4 years and 9 months | Rate of CR/CRh is defined as the percentage of participants achieving a CR or CRh at any time post-treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Duration of Complete Response (CR)/Complete Remission With Partial Hematologic Recovery (CRh) | Up to 4 years and 9 months | 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. |
| Phase 2: Time To CR/CRh | Up to 4 years and 9 months | 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. |
| Phase 2: Event-free survival (EFS) | Up to 4 years and 9 months | 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. |
| Phase 1 and 2: Plasma Concentration of Bleximenib | Up to 4 years and 9 months | Plasma concentration of bleximenib will be reported. |
| Phase 2: Measurable Residual Disease (MRD) Negativity Among Participants Achieving CR/CRh/CRi | Up to 4 years and 9 months | MRD-negative rate is defined as the percentage of participants who are MRD-negative at any timepoint after the first dose of bleximenib in the responders. |
| Phase 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 4 years and 9 months | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. A Serious AE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Phase 2: Number of Participants Reporting Transfusion Independence | Up to 4 years and 9 months | Transfusion independence is defined as independence from red blood cells (RBC) and platelet transfusions during any 56-day interval after receiving study treatment. |
| Phase 2: Overall survival (OS) | Up to 4 years and 9 months | OS is defined from the date of first dose of study treatment to the date of death due to any cause. |
| Phase 1 and 2: Overall Response Rate (ORR) | Up to 4 years and 9 months | ORR is defined as the percentage of participants who achieve any response. |
| Phase 1: Duration of Response (DOR) | Up to 4 years and 9 months | 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. |
| Phase 1 and 2: Time To Response (TTR) | Up to 4 years and 9 months | 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. |
Countries
Australia, Brazil, Canada, China, France, Israel, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
Primary ContactStudy Contact
Outcome results
None listed