RecruitingPhase 3NCT06652438

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML

Randomized Study to Assess Revumenib in Combination With Azacitidine + Venetoclax in Adult Patients With Newly Diagnosed NPM1-mutated or KMT2A-rearranged AML Ineligible for Intensive Chemotherapy


Sponsor

Stichting Hemato-Oncologie voor Volwassenen Nederland

Enrollment

415 participants

Start Date

Mar 31, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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 415 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.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a three-drug combination — revumenib, azacitidine, and venetoclax — for newly diagnosed acute myeloid leukemia (AML) with specific genetic changes (NPM1 mutation or KMT2A rearrangement). These genetic changes are targets for revumenib, and this study aims to see if adding it to a standard two-drug regimen makes treatment more effective. **You may be eligible if...** - You have newly diagnosed AML with a confirmed NPM1 mutation or KMT2A gene rearrangement (verified by a central lab) - You are considered unfit for or unwilling to receive intensive chemotherapy - You are 18 or older - Your heart, kidney, and liver function are adequate **You may NOT be eligible if...** - You have AML without NPM1 mutation or KMT2A rearrangement - You have already received treatment for AML - You have KMT2A partial tandem duplications or deletions (a specific genetic variant) - You have serious heart rhythm problems Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGRevumenib

day 1- 28 per cycle

DRUGPlacebo

day 1- 28 per cycle


Locations(67)

DE-Berlin-CAMPUSBENFRANKLIN

Berlin, Germany

DE-Berlin-CAMPUSVIRCHOW

Berlin, Germany

DE-Berlin-VIVANTESNEUKOLLN

Berlin, Germany

DE-Bochum-RUB

Bochum, Germany

DE-Bonn-UNIBONN

Bonn, Germany

DE-Braunschweig-KLINIKUMBRAUNSCHWEIG

Braunschweig, Germany

DE-Bremen-KBM

Bremen, Germany

DE-Darmstadt-KLINIKUMDARMSTADT

Darmstadt, Germany

DE-Essen-KEM

Essen, Germany

DE-Flensburg-MALTESER

Flensburg, Germany

DE-Frankfurt-KLINIKUMFRANKFURT

Frankfurt, Germany

DE-Freiburg-UNIKLINIKFREIBURG

Freiburg im Breisgau, Germany

DE-Greifswald-UNIGREIFSWALD

Greifswald, Germany

DE-Hamburg-ASKLEPIOSSTGEORG

Hamburg, Germany

DE-Hamburg-UKE

Hamburg, Germany

DE-Hannover-MHHANNOVER

Hanover, Germany

DE-Hannover-SILOAHKRH

Hanover, Germany

DE-Heilbronn-SLK General Information

Heilbronn, Germany

DE-Herne-MARIENHOSPITALHERNE

Herne, Germany

DE-Karlsruhe-KLINIKUMKARLSRUHE

Karlsruhe, Germany

DE-Mainz-UNIMEDIZINMAINZ

Mainz, Germany

DE-Minden-MUEHLENKREISKLINKEN

Minden, Germany

DE-München-IRZTUM

München, Germany

DE-Oldenburg-KLINIKUMOLDENBURG

Oldenburg, Germany

DE-Potsdam-BERGMANN

Potsdam, Germany

DE-Stuttgart-KLINIKUMSTUTTGART

Stuttgart, Germany

DE-Tübingen-MEDUNITUEBINGEN

Tübingen, Germany

DE-Ulm-UNIKLINKULM

Ulm, Germany

DE-Wuppertal-HELIOSGESUNDHEIT

Wuppertal, Germany

NL-Den Bosch-JBZ

's-Hertogenbosch, Netherlands

NL-Amersfoort-MEANDERMC

Amersfoort, Netherlands

NL-Amsterdam-OLVG

Amsterdam, Netherlands

NL-Amsterdam-VUMC

Amsterdam, Netherlands

NL-Arnhem-RIJNSTATE

Arnhem, Netherlands

NL-Breda-AMPHIA

Breda, Netherlands

NL-Delft-RDGG

Delft, Netherlands

NL-Eindhoven-MAXIMAMC

Eindhoven, Netherlands

NL-Enschede-MST

Enschede, Netherlands

NL-Goes-ADRZ

Goes, Netherlands

NL-Groningen-UMCG

Groningen, Netherlands

NL-Leeuwarden-MCL

Leeuwarden, Netherlands

NL-Leiden-LUMC

Leiden, Netherlands

NL-Maastricht-MUMC

Maastricht, Netherlands

NL-Nieuwegein-ANTONIUS

Nieuwegein, Netherlands

NL-Nijmegen-RADBOUDUMC

Nijmegen, Netherlands

NL-Rotterdam-ERASMUSMC

Rotterdam, Netherlands

NL-Den Haag-HAGA

The Hague, Netherlands

NL-Utrecht-UMCUTRECHT

Utrecht, Netherlands

NL-Zwolle-ISALA

Zwolle, Netherlands

Belfasttrust

Belfast, United Kingdom

Birmingham-QE

Birmingham, United Kingdom

Blackpool Victoria

Blackpool, United Kingdom

UH Bristol

Bristol, United Kingdom

University Hospital of Wales

Cardiff, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

St. James UH

Leeds, United Kingdom

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

University of Liverpool

Liverpool, United Kingdom

King's College Hospital

London, United Kingdom

St Bartholomew's Hospital

London, United Kingdom

Christie NHS Foundation Trust

Manchester, United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Churchill Hospital, Oxford

Oxford, United Kingdom

Southampton General Hospital

Southampton, United Kingdom

The Royal Marsden NHSFT

Sutton, United Kingdom

New cross hospital wolverhampton

Wolverhampton, United Kingdom

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NCT06652438


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