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Studies

Interventional Recruiting Phase 3

NCT06652438 on ClinicalTrials.gov

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

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

  • Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland
  • Collaborators: German-Austrian Acute Myeloid Leukemia Study Group, United Kingdom AML Research Network, Beat AML, LLC
  • Enrollment: 448 (Estimated)
  • Study start: 2025-05-05 (Actual)
  • Primary completion: 2029-12-13 (Estimated)
  • Study completion: 2032-08-27 (Estimated)
  • Allocation: Randomized
  • InterventionModel: Single Group
  • Masking: Triple (Participant, Care Provider, Investigator)
  • PrimaryPurpose: Treatment

Brief 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 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.

Conditions

  • Acute Myeloid Leukemia, Adult

Intervention / Treatment

  • Drug: Revumenib
  • Drug: Placebo

Primary Outcome 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 chemotherapy (58 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.

Countries

Australia, Austria, Belgium, Denmark, Estonia, Finland, France, Germany, Ireland, Italy, Lithuania, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom, United States

Locations and Investigators

  • Rigshospitalet, Copenhagen Oe, Denmark
    • Claudia, Schöllkopf
  • Aalborg University Hospital, Aalborg, Denmark
    • Marianne, Tang Severinsen
  • Odense University Hospital, Odense C, Denmark
    • Claus, Marcher
  • Region Midtjylland, Aarhus N, Denmark
    • Hans, Beier Ommen
  • Azienda Sanitaria Locale Di Pescara, Pescara, Italy
    • Giulia, De Luca
  • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino, Turin, Italy
    • Ernesta, Audisio
  • Azienda Ospedaliera Policlinico Universitario Tor Vergata, Rome, Italy
    • Adriano, Venditti
  • Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy
    • Eleonora, De Bellis
  • ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
  • ASL Salerno-PO "Andrea Tortora", Salerno, Italy
    • Catello, Califano
  • Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy
  • Hospital Santa Maria Della Misericordia, Perugia, Italy
    • Valeria, Cardinali
  • Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello, Palermo, Italy
    • Antonio, Mulè
  • Azienda Ospedaliero Universitaria Delle Marche, Ancona, Italy
    • Lorenzo, Brunetti
  • Azienda Sanitaria Territoriale Di Macerata - Ospedale Civitanova Marche, Civitanova Marche, Italy
    • Milena, Mirabile
  • Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico, Bologna, Italy
    • Antonio, Curti
  • Centre Hospitalier Universitaire De Saint Etienne, Saint Priest En Jarez, France
    • Emmanuelle, TAVERNIER
  • Centre Hospitalier Universitaire De Nice, Nice, France
    • Thomas, CLUZEAU
  • Centre Henri Becquerel, Rouen Cedex, France
  • Centre Hospitalier Et Universitaire De Limoges, Limoges Cedex 1, France
    • Pascal, TURLURE
  • Centre Hospitalier Universitaire De Nantes, Nantes, France
    • Pierre, PETERLIN
  • Hopital D'Instruction Des Armees Percy, Clamart, France
    • Jean-Valère, MALFUSON
  • Centre Hospitalier Universitaire De Montpellier, Montpellier Cedex 5, France
    • Ludovic, GABELLIER
  • CHU Besancon, Besancon Cedex, France
    • Yohan, DESBROSSES
  • Les Hopitaux Universitaires De Strasbourg, Strasbourg Cedex 2, France
    • Célestine, SIMAND
  • Centre Hospitalier De Versailles, Le Chesnay Rocquencourt, France
    • Juliette, LAMBERT
  • Centre Hospitalier Universitaire D'Angers, Angers, France
    • Mathilde, HUNAULT-BERGER
  • Centre Hospitalier Universitaire Grenoble Alpes, Grenoble Cedex 9, France
    • Martin, CARRÉ
  • Centre Hospitalier Universitaire De Lille, Lille Cedex, France
    • Céline, BERTHON
  • Assistance Publique Hopitaux De Paris, Creteil Cedex, France
    • Mathieu, LECLERC
  • Centre Hospitalier Universitaire De Bordeaux, Pessac, France
    • Pierre-Yves, DUMAS
  • Hospices Civils De Lyon, Pierre Benite, France
  • Centre Hospital Region Metz Thionville, Metz Cedex 03, France
    • Houria, DEBARRI
  • Centre Hospitalier Universitaire De Caen Normandie, Caen Cedex 9, France
    • Sylvain, CHANTEPIE
  • University Hospital Of Clermont-Ferrand, Clermont-Ferrand, France
    • Romain, GUIEZE
  • Centre Hospitalier Universitaire Amiens Picardie, Amiens Cedex 1, France
    • Delphine, LEBON
  • North Estonia Medical Centre Foundation, Tallinn, Estonia
    • Katrin, Palk
  • Tartu University Hospital, Tartu Linn, Estonia
    • Ain, Kaare
  • Mater Misericordiae University Hospital, Dublin 7, Ireland
    • Michael, Fay
  • St James's Hospital, Dublin 8, Ireland
    • Nina, Orfali
  • Beaumont Hospital, Dublin 9, Ireland
    • John, Quinn
  • University Hospital Galway, Galway, Ireland
    • Tracy, Murphy
  • St Vincent's University Hospital, Dublin 4, Ireland
    • Claire, Andrews
  • University Hospital Waterford, Waterford, Ireland
    • Ezzat, Elhassadi
  • Cork University Hospital, Cork, Ireland
    • Vitaliy, Mykytiv
  • Az St-Jan Brugge-Oostende A.V., Brugge, Belgium
    • Tom, Lodewyck
  • Centre hospitalier universitaire de Liege, Liege, Belgium
    • Adrien, De Voeght
  • Cliniques Universitaires Saint-Luc, Sint-Lambrechts-Woluwe, Belgium
    • Violaine, Havelange
  • Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur, Yvoir, Belgium
    • Elodie, Collinge
  • UZ Brussel, Jette, Belgium
    • Ann, De Becker

And 89 other sites.

Study Officials

  • Gerwin Huls, MD (Principal Investigator) — UMCG/ HOVON