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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
196
Participants will receive bleximenib.
Participants will receive VEN.
Participants will receive AZA.
Number of Participants with Adverse Events (AEs)
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 3 Years 3 months
Number of Participants with Adverse Events (AEs) by Severity
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.
Time frame: Up to 3 Years 3 months
Number of Participants with Dose-limiting Toxicity (DLT)
Number of participants with DLT will be reported according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Time frame: End of Cycle 1 (28 days)
Plasma Concentration of Bleximenib
Plasma samples will be analyzed to determine concentrations of bleximenib using a validated, specific, and sensitive method.
Time frame: Up to 3 Years 3 months
Number of Participants with Depletion of Leukemic Blasts
Number of participants with depletion of leukemic blasts will be reported.
Time frame: Up to 3 Years 3 months
Percentage of Participants who Achieve Complete Remission (CR)
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).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Participants will receive cytarabine.
Participants will receive daunorubicin or idarubicin.
The University of Alabama at Birmingham
Birmingham, Alabama, United States
City of Hope
Duarte, California, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Albert Einstein College Of Medicine
New York, New York, United States
Novant Health
Charlotte, North Carolina, United States
Novant Health Forsyth Medical Center
Winston-Salem, North Carolina, United States
MD Anderson
Houston, Texas, United States
Monash Medical Centre
Clayton, Australia
Peter MacCallum Cancer Centre
Melbourne, Australia
Westmead Hospital
Westmead, Australia
...and 22 more locations
Time frame: Up to 3 Years 3 months
Percentage of Participants who Achieve Complete Remission with Partial Hematologic Recovery (CRh)
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).
Time frame: Up to 3 Years 3 months
Percentage of Participants who Achieve Complete Remission with Incomplete Hematologic Recovery (CRi)
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 \[100,000/mcL\]).
Time frame: Up to 3 Years 3 months
Percentage of Participants who Achieved Overall Response
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).
Time frame: Up to 3 Years 3 months