Leukemia, Myeloid, Acute
Conditions
Brief summary
The purpose of this study is to determine the recommended Phase 2 dose (RP2D) candidate(s) of bleximenib in combination with AML directed therapies (dose selection) and further to evaluate safety and tolerability of bleximenib in combination with AML directed therapies at the RP2D(s) (dose expansion).
Interventions
DRUGBleximenib
Participants will receive bleximenib.
DRUGVenetoclax (VEN)
Participants will receive VEN.
DRUGAzacitidine (AZA)
Participants will receive AZA.
DRUGCytarabine
Participants will receive cytarabine.
Participants will receive daunorubicin or idarubicin.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adolescent participants (defined as greater than or equal to \[\>=\] 12 and less than \[\<\] 18 years of age) are only eligible for the relapsed/refractory (R/R) cohort (Arm A, cohort A4) * Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo or secondary AML; b) relapsed/refractory (Arm A only); c) harboring KMT2A, NPM1, NUP98, or NUP214 alterations; d) Participants may receive emergency leukapheresis and/or cytarabine as cytoreductive therapy according to local practice guidelines * Pretreatment clinical laboratory values meeting the following criteria -listed below: White blood cell (WBC) count: less than or equal to (\<=) 25\*10\^9 per liter (/L), adequate liver and renal function * Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2. Adolescent participants only: Performance status \>70 by Lansky scale (for participants \<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 * Must sign an informed consent form (ICF) indicating participant (or their legally authorized representative) understands the purpose of the study and procedures required for the study and is willing to participate in the study * Willing and able to adhere to the prohibitions and restrictions specified in this protocol
Exclusion criteria
* Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or juvenile myelomonocytic leukemia according to WHO 2016 criteria * Leukemic involvement of the central nervous system * Recipient of solid organ transplant * Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes or that was diagnosed within 6 months prior to the first dose of study treatment including, but not limited to: (a) Myocardial infarction; (b) Severe or unstable angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (\<50 beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood pressure greater than \[\>\] 140/90 millimeters of mercury \[mm Hg\]; (e) Acute neurologic events such as stroke or transient ischemic attack, intracranial or subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events (example, pulmonary embolism) within 1 month prior to the first dose of study treatment ;(g) Congestive heart failure (NYHA class III to IV); (h) Pericarditis or clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k) Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for hypoalbuminemia) * Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia, neutropenia, anemia) from previous anticancer therapy that has not resolved to baseline or to grade 1 or less * Pulmonary compromise that requires the need for supplemental oxygen use to maintain adequate oxygenation * Participants with diagnosis of Fanconi anemia, Kostmann syndrome, Shwachman diamond syndrome, or any other known bone marrow failure syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) | Up to 3 Years 3 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. |
| Number of Participants with Adverse Events (AEs) by Severity | Up to 3 Years 3 months | Number of Participants with AEs by severity will be reported. 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. |
| Number of Participants with Dose-limiting Toxicity (DLT) | End of Cycle 1 (28 days) | Number of participants with DLT will be reported according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of Bleximenib | Up to 3 Years 3 months | Plasma samples will be analyzed to determine concentrations of bleximenib using a validated, specific, and sensitive method. |
| Number of Participants with Depletion of Leukemic Blasts | Up to 3 Years 3 months | Number of participants with depletion of leukemic blasts will be reported. |
| Percentage of Participants who Achieve Complete Remission (CR) | Up to 3 Years 3 months | Percentage of participants who achieve complete Remission (CR) will be reported. CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0\*10\^9/Liter (L) (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL). |
| Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh) | Up to 3 Years 3 months | Percentage of participants who achieve complete remission with partial hematologic recovery (CRh) will be reported. CRh is defined as All criteria of CR with both ANC \>0.5 \* 10\^9/L (500/mcL) and platelet count \>50 \* 10\^9/L (50,000/mcL). |
| Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi) | Up to 3 Years 3 months | Percentage of participants who achieve complete remission with incomplete hematologic recovery (CRi) will be reported. CRi is defined as All CR criteria except for residual neutropenia (\<1.0\*10\^9/L \[1,000/mcL\]) or thrombocytopenia (\<100 \* 10\^9/L \[100,000/mcL\]). |
| Percentage of Participants who Achieved Overall Response | Up to 3 Years 3 months | Percentage of participants who achieve overall response will be reported. Overall response rate (ORR) is defined as the percentage of participants achieving CR, CRh, or CRi, morphologic leukemia-free state (MLFS) or partial remission (PR). |
Countries
Australia, Canada, France, Germany, Italy, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed