Clinical Trial 23595

• Overview

  Study Title:

  A Phase 3 Randomized, Double-blind, Placebo-controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants with Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2A Rearrangements or NPM1 Mutations who are Ineligible for Intensive Chemotherapy

  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 Acute Myeloid Leukemia (AML).

  Objective:

  Primary Objective: To compare the efficacy of bleximenib and VEN+AZA vs VEN+AZA alone. Secondary Objective(s): To further compare the efficacy of bleximenib and VEN+AZA vs VEN+AZA alone. To assess the safety profile. To assess symptoms, functioning, and HRQoL of bleximenib and VEN+AZA vs VEN+AZA alone. To characterize the PK of bleximenib.

• Treatments

  Therapies:

  B-cell lymphoma 2 inhibitor; DNA methylation inhibitor; menin-KMT2A interaction inhibitor

  Medications:

  Azacitidine (5-azacitidine); Bleximenib/placebo (); GDC-0199 (Venetoclax); Venetoclax ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Be 18 years of age or older at the time of informed consent
  • Previously untreated KMT2Ar or NPMlm AML with 2:10% blasts per 2022 ICC criteria based upon local testing. Participants with KMT2A partial tandem duplications or amplifications are NOT eligible. Emergency leukapheresis and/or cytoreductive therapy with hydroxyurea and/or up to a total of 2 g/m2 cytarabine (cytarabine may be administered over a maximum of 5 days , not to exceed 3 doses is permitted prior to first dose of study treatment. Note: cytoreductive therapy with cytarabine should not be given until after the screening bone marrow assessment. Leukapheresis and cytarabine must be discontinued 1 day prior to first dose of study treatment.
  • 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 = 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 with total bilirubin >1.5 to > 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 and for 6 months 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

  Key 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
  • Any active malignancy other than AML (Some exceptions apply)
  • Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function.
  • Had major surgery or had significant traumatic injury within 2 weeks of randomization/enrollment.
  • Live, attenuated vaccine within 4 weeks of randomization
  • Known allergies, hypersensitivity, or intolerance of bleximenib excipients
  • Participants with co-mutations (eg, IDHl) for which there are approved targeted therapies in the front-line setting, unless they do not have access to, or are ineligible for, the targeted therapy.

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