Revumenib for AML with NPM1 or KMT2A Mutations
This study is testing a new treatment for adults with newly diagnosed Acute Myeloid Leukemia (AML) who cannot receive strong chemotherapy. The study is comparing Revumenib along with standard treatments (Azacitidine and Venetoclax) to a placebo (an inactive substance) plus the standard treatments. Revumenib works by blocking a molecule called menin, which is important for the growth of AML cells with specific changes in their DNA (NPM1 or KMT2A mutations). We want to see if Revumenib can help people live longer and achieve complete remission (when signs of cancer disappear). You may be able to join if you have newly diagnosed AML with an NPM1 or KMT2A mutation.
- Study design
- This study plans to enroll 448 adult participants. It is an interventional study, meaning participants will receive a specific treatment.
- What's involved
- Revumenib or placebo is given daily for 28 days per cycle. The trial record does not specify other procedures or visit schedules.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for overall survival and complete remission for up to 58 months after the last patient is included or the first patient is randomized.
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NCT06652438
Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML
Recruiting
PHASE3Ages 18+InterventionalTreatmentStichting Hemato-Oncologie voor Volwassenen NederlandInvestigator-initiated
~448 participants
Updated 2026-08-03 on ClinicalTrials.gov
What's tested:RevumenibPlacebo
At a glance
Recruiting sites
113 of 203 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall survival (OS) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy.
Measured over 58 months after last patient inclusion
+1 more outcome measured
Conditions
Where it's being run
203 sites across 31 statesGermany31
United Kingdom29
Netherlands22
France21
Spain13
Italy12
Australia10
Belgium10
Study leadership
- Gerwin Huls, MD · PRINCIPAL_INVESTIGATOR · UMCG/ HOVON
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
≥ 75 years of age: ineligible for intensive chemotherapy per physician's discretion (with an ECOG performance status 0-2) .
18-74 years: patient is not eligible for standard chemotherapy because any of the following co-morbidities:
ECOG performance status 2 or 3 .
Cardiac history of chronic heart failure requiring treatment; or with an ejection fraction ≤50%; or chronic stable angina.
DLCO ≤ 65% or FEV1 ≤ 65%.
Creatinine clearance ≥ 30 mL/min to \<45 ml/min calculated by the Cockcroft Gault formula.
Moderate hepatic impairment with total bilirubin \> 1.5 to \< 3.0 x upper limit of normal (ULN).
Any other comorbidity that the local physician assesses to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor's (co-) Principal Investigator (written approval must be sent to [email protected] before study enrolment). 5. Patient must have a projected life expectancy of at least 12 weeks (as assessed by the treating physician). 6. Patient must have a white cell blood (WBC) count of \< 25 x 109/L. Hydroxyurea can be used prior to study enrolment to reduce the WBC count to meet this criterion. 7. Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of norm (ULN) or creatinine clearance \>30 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR). 8. Adequate hepatic function as evidenced by:
Serum total bilirubin ≤ 3.0 × ULN unless considered due to Gilbert's disease, or leukemic involvement following written approval by the sponsor (Co-)Principal Investigator (copy in [email protected]).
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement following written approval by the sponsor (Co-)Principal Investigator (copy in [email protected]). 9. Female patient must:
be of nonchildbearing potential: o postmenopausal (defined as at least 1 year without any menses). o documented surgically sterile (e.g. documented hysterectomy, bilateral oophorectomy, bilateral salpingectomy or congenital sterile) or status post hysterectomy (at least 1 month prior to screening).
or, if of childbearing potential (not surgically sterile and not postmenopausal) agree to avoid pregnancy during the study and for 6 months after the final study drug administration.
and have a negative urine or serum pregnancy test at screening.
and, if heterosexually active, agree to consistently apply one highly effective\* method of birth control in combination to a barrier method for the duration of the study and for 6 months after the final study drug administration.
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual activity during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.
agree not to breastfeed starting at screening and throughout the study period.
agree not to donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration. 10. Men must use a latex condom during any sexual contact with women of childbearing potential (WOCBP), even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 6 months after the final study drug administration). In addition, their female partners of childbearing potential must use a highly effective method of birth control. 11. Male patient must not donate sperm starting at screening and throughout the study period and for 6 months after the final study drug administration. 12. Able to understand and willing to sign an informed consent form (ICF). 13. Institutional Review Board/Independent Ethics Committee-approved written informed consent as per national regulations must be obtained from the patient prior to any study-related procedures (including consent for withdrawal of prohibited medication, if applicable).
Exclusion
New York Heart Association (NYHA) class III or IV congestive heart failure
Myocardial infarction
Unstable angina
Severe cardiac arrhythmias
Congenital long QT syndrome of family member with this condition QTcF \>450 msec on screening electrogram for males and \>470msec on screening electrogram for females (mean of triplicate recordings; calculated using Fridericia's correction). 5. Severe obstructive or restrictive ventilation disorder. 6. History of stroke or intracranial hemorrhage within 6 months prior to randomization.
Basal or squamous cell carcinoma of the skin;
Carcinoma in situ of the cervix;
Carcinoma in situ of the breast;
Incidental histologic finding of prostate cancer. 12. Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: patient, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy).
What this trial measures
- Overall survival (OS) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy.58 months after last patient inclusion
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 chemotherapy58 months after the first randomized NPM1-mutated AML patient
Defined as the proportion of NPM1-mutated AML patients who achieve CR at any time-point during protocol therapy.