Newly diagnosed KMT2A-rearranged or NPM1-mutant Acute Myeloid Leukemia
Conditions
Interventions
Experimental: Arm 1: Bleximenib in combination with remission induction and consolidation therapy, followed by bleximenib maintenance therapy. Treatment will continue until PD, unacceptable toxicity o
Sponsors
Hori Mariko
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: >=18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent. New diagnosis of AML (>=10% blasts in BM or peripheral blood) with mutated NPM1 or with recurring rearrangements involving KMT2A according to ICC 2022 criteria. Considered eligible for intensive chemotherapy. WHO/ECOG performance status =<2. Adequate renal and hepatic functions prior to randomization.
Exclusion criteria
Exclusion criteria: 1. Prior (chemo-)therapy for AML, including prior treatment with hypomethylating agents. 2. Known active leukemic involvement of the central nervous system (CNS). 3. Recipient of solid organ transplant. 4. Cardiac disease: a. Any of the following within 6 months of randomization: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (NYHA Class III or IV), uncontrolled or symptomatic arrhythmias, stroke, or transient ischemic attack. b. QTc interval using Fridericias formula (QTcF) >= 470 ms. Prolonged QTc interval associated with bundle branch block or pacemaking is permitted. c. Left ventricular ejection fraction (LVEF) = 500 mg/m^2. 5. Chronic respiratory disease requiring supplemental oxygen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess if treatment with bleximenib, as compared with placebo, in combination with remission induction chemotherapy, prolongs event-free survival (EFS) measured from the time from randomization to failure to achieve CR after remission induction, hematologic relapse after achieving CR, or death, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Overall Survival (OS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy - Rates of CR, CRh, CRi in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy - Prolongation of CR (DoCR) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy - Percentage of participants undergoing an allo-SCT in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy | — |
Countries
Germany, Japan, Netherlands, United States
Contacts
Public ContactMariko Hori
PPD-SNBL K. K.
Outcome results
None listed