Leukemia, Myeloid, Acute
Conditions
Brief summary
The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine (AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants with newly diagnosed Acute Myeloid Leukemia (AML) with a mutation in the NPM1 or KMT2A gene.
Interventions
DRUGBleximenib
Bleximenib will be administered orally.
DRUGVenetoclax (VEN)
VEN will be administered orally.
DRUGAzacitidine (AZA)
AZA will be administered intravenously or subcutaneously.
DRUGPlacebo
Placebo will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be 18 years of age or older at the time of informed consent * Previously untreated lysine N-methyltransferase 2A gene rearranged (KMT2Ar) or nucleophosmin 1 gene mutated (NPM1m) acute myeloid leukemia (AML) with greater than or equal to (\> or =) 10% bone marrow blasts per 2022 international Consensus Classification criteria * Ineligible for intensive chemotherapy based on the following criteria: a) \>= 75 years of age and ineligible per physician's discretion, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, b) \>=18 to \<75 years of age with \>= 1 of the following comorbidities: i) ECOG performance status of 2, ii) Severe cardiac disorder, iii) Severe pulmonary disorder, iv) Renal impairment, v) Moderate hepatic impairment vi) Comorbidity that, in the investigator's opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented before enrollment as defined in the protocol. Ineligibility for intensive chemotherapy should be explicitly approved by a multidisciplinary team in countries in which this process is standard of care * Participants must have adequate hepatic and renal function * A female participant must agree not to be pregnant, breast-feed, plan to become pregnant and use protocol-specified contraception while enrolled in this study and for 6 months after the last dose of study treatment * A male participant must agree to use protocol-specified contraception while enrolled in this study for at least 90 days after the last dose of study treatment * Must sign an informed consent form indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study
Exclusion criteria
* Diagnosis of acute promyelocytic leukemia (APL) * Known active leukemic involvement of the central nervous system (CNS) * Recipient of solid organ transplant * Any cardiac disorders such as heart attack, uncontrolled/unstable chest pain, congestive heart failure, uncontrolled or symptomatic irregular heartbeat, blockage of a blood vessel to brain, or transient ischemic (decreased oxygen in tissue) attack within 6 months of randomization * Active infectious hepatitis * Live, attenuated vaccine within 4 weeks of randomization * Known allergies, hypersensitivity, or intolerance of bleximenib, azacitidine, or venetoclax excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve Complete Remission (CR) | Up to 4 years and 1 month | 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 (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL). |
| Overall Survival (OS) | Up to 4 years and 1 month | Overall survival time is defined as the time duration from the date of randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | Up to 4 years and 1 month | EFS is defined as the time from randomization to treatment failure, relapse, or death due to any cause, whichever occurs first. |
| Duration of CR | Up to 4 years and 1 month | Duration of CR will be estimated among responders from the date of initial documentation of CR, to the date of first documented evidence of relapse, or death due to any cause, whichever occurs first, respectively. |
| Time to CR | Up to 4 years and 1 month | Time to CR is defined as time from randomization to first documented response. |
| Rate of CR Without Measurable Residual Disease (MRD-) | Up to 4 years and 1 month | Rate of CR MRD- is defined as percentage of participants who have achieved CR without MRD. |
| Percentage of Participants who Achieved Transfusion Independence | Up to 4 years and 1 month | Transfusion independence is defined as lack of requirement for red blood cell (RBC) and platelet transfusions during any 56-day period. |
| Percentage of Participants with Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT) | Up to 4 years and 1 month | Allo-HSCT rate is defined as the percentage of participants who have undergone allo-HSCT after randomization. |
| Number of Participants with Adverse Events (AEs) | Up to 4 years and 1 month | 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. 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 Abnormalities in Clinical Laboratory Parameters | Up to 4 years and 1 month | Participants with abnormalities in clinical laboratory parameters will be reported. |
| Serum Concentration of Bleximenib | Up to 4 years and 1 month | Serum samples will be analyzed to determine concentrations of bleximenib. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, Israel, Italy, Japan, Mexico, Poland, Portugal, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed