Treatment of patients with newly diagnosed AML who are not eligible for intensive chemotherapy has remained an area of high unmet medical need. The combination therapy with two medicines, azacitidine and venetoclax, is the usual plan of action. This has brought significant progress in the treatment, but it nevertheless is not curative and the disease does relapse over time.
Revumenib blocks a specific molecule called menin in the cell nucleus. Some types of AML are reliant on menin working properly. These are leukemia cells with a change in the DNA, i.e. a mutation in the NPM1 or KMT2A gene. Revumenib can prevent the production of these types of leukemia cells by disrupting the production of this menin.
The current study investigates whether adding revumenib to the combination therapy improves the prognosis for AML patients with a mutation in the NPM1 or KMT2A gene.
This is a randomized, double-blind, placebo-controlled clinical study where subjects will be treated until disease progression, or development of side effects or death. From the moment of inclusion of the last patient, there will be a 4-year observational follow-up study in order to register survival duration and follow-up visits.
Approximately 448 previously untreated patients with a mutation in the NPM1 or KMT2A gene and with newly diagnosed AML, who are not eligible for intensive chemotherapy. Patients must be ≥18 years of age.
Patient with newly diagnosed NPM1-mutated AML, consistent with NPM1c, according to the 2022 International Consensus Classification (i.e. ≥ 10% blasts).
Central confirmation of NPM1 mutation or KMT2A rearrangement in one of the dedicated central genetic laboratories.
Age ≥ 18 years, no upper age limit.
≥ 75 years of age: ineligible for intensive chemotherapy per physician's discretion (with an ECOG performance status 0-2) .
New York Heart Association (NYHA) class III or IV congestive heart failure
Myocardial infarction
Unstable angina
Severe cardiac arrhythmias
Single group
Revumenib
Drugday 1- 28 per cycle
Placebo
Drugday 1- 28 per cycle
Overall survival (OS) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy.
To assess if treatment with revumenib, in combination with azacitidine and venetoclax, prolongs overall survival (OS) measured from the date of randomization to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
Rate of CR in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy
Defined as the proportion of NPM1-mutated AML patients who achieve CR at any time-point during protocol therapy.
Event-free survival (EFS) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy.
Assess if treatment with revumenib, in combination with azacitidine and venetoclax, prolongs event-free survival (EFS); measured from the date of randomization to the date of treatment failure, hematologic relapse from CR/CRh or death from any cause, whichever occurs first. Treatment failure is defined as lack of obtaining either CR or CRh by week 24.
Rate of CR/CRh in adult patients with newly diagnosed NPM1mutated AML ineligible for intensive chemotherapy,
Defined as the proportion of NPM1-mutated AML patients who achieve CR or CRh at any time-point during protocol therapy.
Rate of response (CRh and CR/CRi) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy
Rate of response (CRh and CR/CRi) is defined as the proportion of patients with response at any time-point during protocol therapy.
Rates of CRMRD-, CR/CRhMRD-, and CR/CRiMRD- assessed by quantitative PCR of bone marrow in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy
defined as the proportion of NPM1-mutated AML patients with CRMRD-, CR/CRhMRD- and CR/CRiMRD- by PCR of bone marrow, respectively, at any time-point during protocol therapy.
Click on the lead sponsor to view all of their trials.
Stichting Hemato-Oncologie voor Volwassenen Nederland
Lead sponsor
German-Austrian Acute Myeloid Leukemia Study Group
Collaborator
United Kingdom AML Research Network
Collaborator
Beat AML, LLC
Collaborator