AzTrials
AzTrials

Acute Myeloid Leukemia, AdultPhase 3NCT06652438

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

A Phase 3 study testing Revumenib in people with Acute Myeloid Leukemia, Adult, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 201 sites in 18 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia, Adult
What is being tested?
Revumenib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
448 participants
Where
201 sitesin 18 countries
Study dates
5 May 2025to 27 Aug 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In order to be eligible to participate in this study, a patient must meet all of the following criteria:
  • Patient with newly diagnosed NPM1-mutated AML, consistent with NPM1c, according to the 2022 International Consensus Classification (i.e. ≥ 10% blasts).
  • OR Patient with newly diagnosed KMT2A-rearranged AML according to the 2022 International Consensus Classification (i.e. ≥ 10% blasts). KMT2A partial tandem duplications or deletions are NOT eligible.
  • Of note: in case both NPM1 and IDH1 are mutated and both EVOLVE-1 (HO173) and EVOLVE-2 (HO177) are open for inclusion at your site, then patients can only be included in the EVOLVE-1 trial (HO173)
  • Central confirmation of NPM1 mutation or KMT2A rearrangement in one of the dedicated central genetic laboratories.
  • Age ≥ 18 years, no upper age limit.
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  • Patient is ineligible for intensive induction chemotherapy by meeting at least 1 of the following criteria:
  • ≥ 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 HO177@erasmusmc.nl before study enrolment).
  • Patient must have a projected life expectancy of at least 12 weeks (as assessed by the treating physician).
  • 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.
  • 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).
  • 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 HO177@erasmusmc.nl).
  • 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 HO177@erasmusmc.nl).
  • 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.
  • Highly effective forms of birth control include
  • Consistent and correct usage of established hormonal contraceptives that inhibit ovulation for at least 1 month prior to taking study drug. (hormonal contraception is only a highly effective method of birth control, if a combined [estrogen and progestogen containing] hormonal contraception or a progestogen-only hormonal contraception - both associated with inhibition of ovulation - is used.
  • Established intrauterine device (IUD) or intrauterine system (IUS)
  • Bilateral tubal occlusion
  • Vasectomy - a vasectomy is highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.
  • Male is sterile due to a bilateral orchiectomy.
  • 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.
  • List is not all inclusive. Prior to enrolment, the investigator is responsible for confirming patient will utilize highly effective forms of birth control in combination with a barrier method according to locally accepted standards during the protocol defined period.
  • 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.
  • 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.
  • Male patient must not donate sperm starting at screening and throughout the study period and for 6 months after the final study drug administration.
  • Able to understand and willing to sign an informed consent form (ICF).
  • 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).

Who cannot join

  • Subject has previously been treated for AML; a treatment period with hydroxyurea to control WBC counts is allowed; prior treatment with a hypomethylating agent for MDS-EB is not allowed; prior treatment with erythropoiesis-stimulating agents or luspatercept for MDS is allowed.
  • 2. Acute promyelocytic leukemia (APL) with t(15;17)(q24.1;q21.2); PML-RARA; or one of the other pathognomonic variant chromosomal translocations / fusion genes. 3. AML with BCR-ABL1; or myeloid blast crisis of CML. 4. Significant active cardiac disease within 3 months prior to the start of study treatment, including:
  • New York Heart Association (NYHA) class III or IV congestive heart failure
  • Myocardial infarction
  • Unstable angina
  • Severe cardiac arrhythmias
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  • 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.
  • 7. Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening. 8. Active infection, including hepatitis B or hepatitis C or Human Immunodeficiency Virus (HIV) infection, that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or which could expose the patient to undue risk through the participation in the clinical trial; an infection controlled with an approved antibiotic/ antiviral/ antifungal treatment that is not a strong or moderate CYP3A inducer is allowed. Patients with COVID-19 infection can be enrolled, if the patient has no symptoms and was tested negative twice by PCR test prior to inclusion in the trial. 9. Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation. 10. Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.
  • 11. Patient with a currently active second malignancy. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at < 30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed:
  • 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).
  • 13. Severe neurological or psychiatric disorder interfering with ability to give an informed consent.
  • 14. Contraindication to AZA or VEN (as per Summary of Product Characteristics (SmPC)).
  • 15. Patient weighing <40 kg at registration. 16. Participation in other prospective studies with anti-leukemic and/or investigational agents.
  • 17. Patient taking Dabigatran unless they can be transferred to other medications within ≥5 half-lives prior to dosing. Patients taking other P-gP transporter-sensitive medications (see Appendix H) should be properly monitored during the study if they cannot be transferred to other medications.
  • 18. Patient taking known strong cytochrome P450 (CYP) 3A4 inducers (see Appendix G), unless they can be transferred to other medications within ≥5 half-lives prior to dosing.
  • 19. The patient is a pregnant or lactating woman, or plans to become pregnant during the study.
  • 20. Patient who has once been screened and randomized into this HO177 trial but was considered ineligible cannot re-enter this trial at a later date.

Trial locations and contacts

201 sites in 18 countries. Contact the study team or a site near you to ask about taking part.

Gerwin Huls, MD contact

+31-(0)107041560

HOVON@erasmusmc.nl

Paresh Vyas, MD contact

+44(0)7817248950

paresh.vyas@imm.ox.ac.uk

201 sites in 18 countries

Germany31 sites, 31 recruiting

  • DE-Berlin-CAMPUSBENFRANKLIN

    Berlin

    Jan Krönke, Prof.

    Not yet recruiting

  • DE-Berlin-CAMPUSVIRCHOW

    Berlin

    Jan Krönke, Prof.

    Not yet recruiting

  • DE-Berlin-VIVANTESNEUKOLLN

    Berlin

    Maike de Wit

    Not yet recruiting

  • DE-Bochum-RUB

    Bochum

    R. Schroers, Dr.

    Recruiting

  • DE-Bonn-UNIBONN

    Bonn

    Lino Teichmann, Dr.

    Not yet recruiting

  • DE-Braunschweig-KLINIKUMBRAUNSCHWEIG

    Braunschweig

    Juergen Krauter, Prof. Dr.

    Not yet recruiting

  • DE-Bremen-KBM

    Bremen

    Bernd Hertenstein, Prof.

    Not yet recruiting

  • DE-Darmstadt-KLINIKUMDARMSTADT

    Darmstadt

    Helga Bernhard, Dr.

    Not yet recruiting

  • DE-Essen-KEM

    Essen

    Stephanie Harsdorf, von, Dr.

    Not yet recruiting

  • DE-Flensburg-MALTESER

    Flensburg

    Angela Krackhardt, Prof.

    Recruiting

  • DE-Freiburg-UNIKLINIKFREIBURG

    Freiburg im Breisgau

    Michael Lübbert, Prof. Dr.

    Not yet recruiting

  • DE-Greifswald-UNIGREIFSWALD

    Greifswald

    Adrian Schwarzer, Prof. Dr.

    Recruiting

  • Halle-UMH

    Halle

    M. Heuser

    M Heuser

    Recruiting

  • DE-Hamburg-ASKLEPIOSSTGEORG

    Hamburg

    Ahmet Elmaagacli, Prof.

    Recruiting

  • DE-Hamburg-UKE

    Hamburg

    Wlater Fiedler, Prof. Dr.

    Not yet recruiting

  • DE-Hannover-MHHANNOVER

    Hanover

    Felicitas Thol, Prof. Dr.

    Recruiting

  • DE-Heilbronn-SLK General Information

    Heilbronn

    Markus Lindauer, Dr.

    Recruiting

  • DE-Herne-MARIENHOSPITALHERNE

    Herne

    Amin Turki, Dr.

    Recruiting

  • DE-Karlsruhe-KLINIKUMKARLSRUHE

    Karlsruhe

    Mark Ringhoffer, Prof. Dr.

    Not yet recruiting

  • DE-Magdeburg-OVGU

    Magdeburg

    M. Berisha

    Recruiting

  • DE-Mainz-UNIMEDIZINMAINZ

    Mainz

    Michael Kühn, Mr. Dr.

    Recruiting

  • DE-Minden-MUEHLENKREISKLINKEN

    Minden

    Kai Wille, Dr.

    Not yet recruiting

  • DE-München-IRZTUM

    München

    Katharina Götze, Prof.

    Not yet recruiting

  • DE-Oldenburg-KLINIKUMOLDENBURG

    Oldenburg

    Andreas Voss, Dr.

    Recruiting

  • DE-Potsdam-BERGMANN

    Potsdam

    Su-Hyeon Kim, Dr.

    Not yet recruiting

  • DE-Regensburg-UKR

    Regensburg

    H. Poeck

    Not yet recruiting

  • DE-Rostock-MUROSTOCK

    Rostock

    C. Junghanß

    Not yet recruiting

  • DE-Stuttgart-KLINIKUMSTUTTGART

    Stuttgart

    J. Schleicher, Dr.

    Not yet recruiting

  • DE-Tübingen-MEDUNITUEBINGEN

    Tübingen

    Claudia Lengerke, Prof.

    Not yet recruiting

  • DE-Ulm-UNIKLINKULM

    Ulm

    Hartmut Döhner, Prof.

    Recruiting

  • DE-Wuppertal-HELIOSGESUNDHEIT

    Wuppertal

    Silke Schostok, Dr.

    Not yet recruiting

Other trials in Germany

United Kingdom29 sites, 29 recruiting

  • Belfasttrust

    Belfast

    N. Cunningham

    Not yet recruiting

  • Birmingham-QE

    Birmingham

    V Murthy

    Not yet recruiting

  • Blackpool Victoria

    Blackpool

    P. Cahalin

    Recruiting

  • UK-Bodelwyddan-BCUHB

    Bodelwyddan

    E. Heartin

    Not yet recruiting

  • UK-Bristol-BRISTOLCENTRE

    Bristol

    P. Mehta

    Recruiting

  • University Hospital of Wales

    Cardiff

    S. Knapper

    Recruiting

  • UK-Portsmouth-QUEENALEXANDRA

    Cosham

    Edward Belsham, Dr.

    Recruiting

  • UK-Coventry-UHCOVENTRYANDWARWICKSHIRE

    Coventry

    I. Qureshi, Dr.

    Recruiting

  • UK-Derby-ROYALDERBYHOSPITAL

    Derby

    Dr. I. Amott

    Not yet recruiting

  • UK-Edinburgh-WGH

    Edinburgh

    V. Campbell

    Not yet recruiting

  • Beatson West of Scotland Cancer Centre

    Glasgow

    M Copland

    Recruiting

  • UK-Harrow-NORTHWICK

    Harrow

    S. Arami

    Not yet recruiting

  • UK-Hull-CASTLEHILL

    Hull

    S. Green, Dr.

    Recruiting

  • St. James UH

    Leeds

    M. Jain

    Recruiting

  • University Hospitals of Leicester NHS Trust

    Leicester

    A. Tsoulkani

    Recruiting

  • King's College Hospital

    London

    P. Krishnamurthy

    Recruiting

  • St Bartholomew's Hospital

    London

    S. Charrot, Dr.

    Recruiting

  • University College Hospital

    London

    K. Stringaris, Dr.

    Recruiting

  • Christie NHS Foundation Trust

    Manchester

    M. Dennis

    Recruiting

  • UK-Manchester-ROYALINFIRMARY

    Manchester

    E. Tholouli, Dr.

    Recruiting

  • The Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle

    G. Jones

    Recruiting

  • Nottingham University Hospitals NHS Trust

    Nottingham

    G. Errico

    Recruiting

  • Churchill Hospital, Oxford

    Oxford

    P. Vyas

    Recruiting

  • Southampton General Hospital

    Southampton

    S. Narayanan

    Recruiting

  • UK-Stoke on Trent-UHNM

    Stoke-on-Trent

    S. Pillai

    Not yet recruiting

  • The Royal Marsden NHSFT

    Sutton

    D. Taussig

    Recruiting

  • UK-Swindon-GWH

    Swindon

    A. Sternberg

    Not yet recruiting

  • UK-Cornwall-RCH

    Truro

    R. Witherall

    Recruiting

  • New cross hospital wolverhampton

    Wolverhampton

    R. Whitmill

    Recruiting

Other trials in United Kingdom

Netherlands22 sites, 22 recruiting

  • NL-Den Bosch-JBZ

    's-Hertogenbosch

    A. Herbers

    Recruiting

  • NL-Amersfoort-MEANDERMC

    Amersfoort

    Maarten Corsten

    Recruiting

  • Amsterdamumc

    Amsterdam

    D.C. de Leeuw

    Recruiting

  • NL-Amsterdam-OLVG

    Amsterdam

    W.E. Terpstra

    Recruiting

  • NL-Arnhem-RIJNSTATE

    Arnhem

    Marloes Cuijpers

    Recruiting

  • NL-Breda-AMPHIA

    Breda

    Roel Fiets

    Recruiting

  • NL-Delft-RDGG

    Delft

    R.E. Brouwer

    Recruiting

  • NL-Dordrecht-ASZ

    Dordrecht

    P.E. Westerweel, Dr.

    Recruiting

  • NL-Dordrecht-ASZ

    Dordrecht

    P.E. Westerweel

    Recruiting

  • NL-Eindhoven-MAXIMAMC

    Eindhoven

    L.W. Tick

    Recruiting

  • NL-Enschede-MST

    Enschede

    T.J.F. Snijders

    Recruiting

  • NL-Goes-ADRZ

    Goes

    Y. Bilgin

    Recruiting

  • NL-Groningen-UMCG

    Groningen

    Gerwin Huls

    Recruiting

  • NL-Leeuwarden-FRISIUSMC

    Leeuwarden

    Bas Franken

    Recruiting

  • NL-Leiden-LUMC

    Leiden

    J.H. Veelken

    Recruiting

  • NL-Maastricht-MUMC

    Maastricht

    C.H.M.J. van Elssen

    Recruiting

  • NL-Nieuwegein-ANTONIUS

    Nieuwegein

    Okke de Weerdt

    Recruiting

  • NL-Nijmegen-RADBOUDUMC

    Nijmegen

    J. Janssen

    Recruiting

  • NL-Rotterdam-ERASMUSMC

    Rotterdam

    M. Jongen-Lavrencic

    Recruiting

  • NL-Den Haag-HAGA

    The Hague

    D. Lammeren, van Venema

    Recruiting

  • NL-Utrecht-UMCUTRECHT

    Utrecht

    A. van Rhenen

    Recruiting

  • NL-Zwolle-ISALA

    Zwolle

    G. Sluis, van, Dr.

    Recruiting

Other trials in Netherlands

France21 sites, 21 recruiting

  • FR-Amiens-CHUAMIENS

    Amiens

    D. Lebon

    Not yet recruiting

  • FR-Angers-CHUANGERS

    Angers

    M. Prof. Hunault

    Recruiting

  • FR-Bayonne-CHCOTEBASQUE

    Bayonne

    L. Harmony

    Not yet recruiting

  • FR-Besançon Cedex-JEANMINJOZ

    Besançon

    Y. Desbrosses

    Not yet recruiting

  • FR-Caen-CHUCAEN

    Caen

    S. Chantepie

    Recruiting

  • FR-Clamart-HIAPERCY

    Clamart

    J.V. Malfuson

    Recruiting

  • FR-Clermont Ferrand-ESTAING

    Clermont-Ferrand

    R. Guieze

    Not yet recruiting

  • FR-Créteil cedex-CHUMONDOR

    Créteil

    Mathieu Leclerc

    Recruiting

  • FR-Grenoble cedex 9-CHUGRENOBLE

    Grenoble

    M. Carre

    Recruiting

  • FR-Le Chesnay cedex-CHVERSAILLES

    Le Chesnay

    J. Lambert, LL

    Not yet recruiting

  • FR-Lille-CHULILLE

    Lille

    C. Berthon

    Not yet recruiting

  • FR-Limoges-CHULIMOGES

    Limoges

    P. Turlure

    Not yet recruiting

  • FR-Metz-Cedex-MERCY

    Metz

    H. Debarri

    Recruiting

  • FR-Montpellier-STELOI

    Montpellier

    G. Ludovic

    Recruiting

  • FR-Nantes-CHUNANTES

    Nantes

    P. Peterlin

    Not yet recruiting

  • FR-Nice-LARCHET

    Nice

    T. Cluzeau

    Recruiting

  • FR-Pessac Cedex-CHUBORDEAUX

    Pessac

    P. Dumas

    Recruiting

  • FR-Lyon Pierre Benite cedex-LYONSUD

    Pierre-Bénite

    M. Heiblig

    Recruiting

  • FR-Rouen cedex-BECQUEREL

    Rouen

    E. Lemasle

    Not yet recruiting

  • FR-Saint-Priest-en-Jarez-STETIENNE

    Saint-Priest-en-Jarez

    E. Tavernier

    Recruiting

  • FR-Strasbourg cedex-HAUTEPIERRE

    Strasbourg

    Célestine Simand

    Not yet recruiting

Other trials in France

United States14 sites, 14 recruiting

  • US-Atlanta GA-EMORY

    Atlanta, Georgia, 30322

    William Blum

    Recruiting

  • US-Baltimore MD-UMGCCC

    Baltimore, Maryland, 21201

    M. Baer

    Recruiting

  • US-Chapel Hill-UNCNORTHCAROLINA

    Chapel Hill, North Carolina, 27514

    J. Zeidner

    Recruiting

  • US-Cincinnati OH-CINCY

    Cincinnati, Ohio, 45219

    E. Curran

    Recruiting

  • US-Colombus OH-OSU

    Columbus, Ohio, 43210

    S. Handa

    Recruiting

  • US-Dallas TX-SOUTHWESTERN

    Dallas, Texas, 75390

    Y Madanat

    Not yet recruiting

  • US-Kansas City KS-KUMC

    Fairway, Kansas, 66205

    T Lin

    Not yet recruiting

  • US-Jacksonville FL-MAYOFL

    Jacksonville, Florida, 32224

    J. Foran

    Not yet recruiting

  • US-Los Angeles CA-UCLA

    Los Angeles, California, 90095

    G. Schiller

    Not yet recruiting

  • US-Pittsburgh PA-PITT

    Pittsburgh, Pennsylvania, 15232

    A. Im

    Recruiting

  • US-Portland OR-OHSU

    Portland, Oregon, 97239

    R. Swords

    Not yet recruiting

  • US-Rochester MN-MAYOMN

    Rochester, Minnesota, 55905

    A. Al-Kali

    Not yet recruiting

  • US-San Francisco CA-UCSF

    San Francisco, California, 94143

    R. Olin

    Not yet recruiting

  • US-Wheeling WV-WVU

    Wheeling, West Virginia, 26003

    T. Bhatnagar

    Recruiting

Other trials in United States

Spain13 sites, 13 recruiting

  • ES-Alicante-BALMIS

    Alicante

    Dr. C. Gil

    Not yet recruiting

  • ES-Barcelona-CLINICUB

    Barcelona

    J. Esteve Reyner, Dr.

    Recruiting

  • ES-Barcelona-GERMANTRIALS

    Barcelona

    S. Vives Polo

    Recruiting

  • ES-Barcelona-ICODURANREYNALS

    Barcelona

    M.S. Arnan

    Recruiting

  • ES-Barcelona-MUTUATERRASSA

    Barcelona

    F. Vall-Llovera Calmet, Dr.

    Recruiting

  • ES-Barcelona-PARCDESALUTMAR

    Barcelona

    S. Garcia Avila

    Recruiting

  • ES-Barcelona-SANTPAU

    Barcelona

    A. Garrido Diaz, Dr.

    Recruiting

  • ES-Girona-ICOGIRONA

    Girona

    R. Coll Jorda, Dr.

    Recruiting

  • ES-Lleida-ICSVILANOVA

    Lleida

    G. Garcia Guiñon, Dr.

    Recruiting

  • ES-Madrid-CSGREGORIOMARANON

    Madrid

    G. RODRIGUEZ-MACIAS

    Recruiting

  • ES-Palma-SSIB

    Palma de Mallorca

    A. Sampol Mayol, Dr.

    Recruiting

  • ES-Tarragona-JOAN

    Tarragona

    A. Aguilar Balta, Dr.

    Recruiting

  • ES-Valencia-MALVARROSA

    Valencia

    M. Tormo, Dr.

    Recruiting

Other trials in Spain

Italy12 sites, 12 recruiting

  • IT-Ancona-MARCHE

    Ancona

    L. Brunetti

    Recruiting

  • IT-Bologna-MALPHIGI

    Bologna

    Dr Antonio Curti

    Not yet recruiting

  • IT-Civitanova Marche-AZURZONA

    Civitanova Marche

    Milena Mirabile

    Not yet recruiting

  • IT-Milano-NIGUARDA

    Milan

    Dr Roberto Cairoli

    Not yet recruiting

  • IT-Pagani-TORTORA

    Pagani

    C. Califano

    Not yet recruiting

  • IT-Palermo-CERVELLO

    Palermo

    Antonino Mulè

    Not yet recruiting

  • IT-Perugia-OSPEDALEPERUGIA

    Perugia

    Maria Paola Martelli

    Not yet recruiting

  • IT-Pescara-AUSLPESCARA

    Pescara

    Prassede Salutari

    Not yet recruiting

  • IT-Roma-SAPIENZA

    Roma

    Dr Massimo Breccia

    Not yet recruiting

  • IT-Roma-TORVERGATA

    Roma

    Dr Adriano Venditti

    Not yet recruiting

  • IT-Torino-CITTADELLASALUTE

    Torino

    Dr Ernesta Audisio

    Not yet recruiting

  • IT-Trieste-MAGGIORETRIESTE

    Trieste

    Eleonora de Bellis

    Not yet recruiting

Other trials in Italy

Australia10 sites, 9 recruiting

  • AU-Adelaide-RAH

    Adelaide

    B. Hiwase

    Not yet recruiting

  • AU-Birtinya-SUNSHINECOASTUH General Information

    Birtinya

    J. Conn

    Not yet recruiting

  • AU-Brisbane-RBWH

    Brisbane

    S. Lane

    Recruiting

  • AU-Douglas-TOWNSVILLE

    Douglas

    H.C. Lai

    Not yet recruiting

  • AU-Melbourne-ALFRED

    Melbourne

    S. Loo

    Recruiting

  • AU-Melbourne-MONASH

    Melbourne

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About this study

Official title: 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

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.

Read more

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.

Being tested
Revumenib, Placebo
Keywords
newly AML diagnosed, NPM1, KMT2A
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RevumenibDrug

    day 1- 28 per cycle

  • PlaceboDrug

    day 1- 28 per cycle

Study groups in NCT06652438
Study groupRoleWhat they receive
Revumenib-placeboPlacebo comparatorday 1-28 Placebo Treatment will be on a continuous 28-day cycle schedule and continued until disease progression, development of unacceptable toxicity, death, withdrawal by subject or other protocol defined criteria for discontinuation (whichever comes first).
Receives: Drug: Placebo
RevumenibExperimentalday 1-28 Revumenib Treatment will be on a continuous 28-day cycle schedule and continued until disease progression, development of unacceptable toxicity, death, withdrawal by subject or other protocol defined criteria for discontinuation (whichever comes first).
Receives: Drug: Revumenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 58 months after last patient inclusion

  2. 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.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

Secondary outcomes (9)

  1. 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.

    Measured: 58 months after the first NPM1-mutated AML patient has been randomized

  2. 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.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  3. 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.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  4. 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.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  5. Rates of CRMRD-, CR/CRhMRD-, and CR/CRiMRD- assessed by quantitative PCR of peripheral blood 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 peripheral blood, respectively, at any time-point during protocol therapy.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  6. Time to achievement of response (CR, CR/CRh and CR/CRi) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy

    measured as the time from randomization to 1st occurrence of response.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  7. Duration of response (CR, CR/CRh and CR/CRi; DoR) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy

    measured from the date of achievement of response until the date of hematologic relapse or death from any cause.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  8. QoL in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy

    Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores are transformed to a 0 to 100 scale. For the Global Health Status/Quality of Life scale and functional scales, higher scores indicate better quality of life/functioning; for symptom scales, higher scores indicate worse symptoms.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

  9. QoL in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy

    Health-related quality of life was assessed using the EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L). The EQ-5D-5L descriptive system generates a health utility index score based on country-specific value sets. Higher utility values indicate better health status. The EQ Visual Analogue Scale (EQ VAS), if reported, ranges from 0 to 100, where higher scores indicate better perceived health.

    Measured: 58 months after the first randomized NPM1-mutated AML patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2024
  2. Study start5 May 2025
  3. Primary completion13 Dec 2029 (estimated)
  4. Study completion27 Aug 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
448 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06652438
Sponsor's protocol ID
HO177
Other IDs
2024-512733-32-00
Status last verified
Aug 2026
First submitted
2 Oct 2024
Last updated
2 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: According to the current publication policy the protocol and Statistical Analysis Plan ( SAP) will be shared. The principal Investigators can be contacted for IPD sharing after the publication of the study results. According to 'HOVON sample and/or Data request Form' the HOVON director; chair of the HOVON Acute Myeloid Leukemic working group, the study PI and Coordinating Investigator should approve data/sample sharing.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Revumenib in people with Acute Myeloid Leukemia, Adult, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 201 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 201 sites in Germany, United Kingdom, Netherlands, France, United States and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gerwin Huls, MD (+31-(0)107041560, HOVON@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (OS) in adult patients with newly diagnosed NPM1-mutated AML ineligible for intensive chemotherapy. (time frame: 58 months after last patient inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06652438.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.

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