A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation
NCT ID: NCT04065399
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
413 participants
INTERVENTIONAL
2019-11-05
2027-12-15
Brief Summary
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In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.
Detailed Description
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Arm A: Participants not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers or fluconazole.
Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
Arm C: Participants receiving revumenib and cobicistat.
Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib:
* Cohort 2A: Participants with KMT2Ar acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL)
* Cohort 2B: Participants with KMT2A AML
* Cohort 2C: Participants with NPM1m AML
Conditions
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Keywords
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Study Design
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NA
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Revumenib
Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in 1 of 6 dose-escalation arms:
* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole
* Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis
* Arm C: Participants receiving revumenib and cobicistat
* Arm D: Participants receiving fluconazole for antifungal prophylaxis
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers
* Arm F: Participants receiving isavuconazole for antifungal prophylaxis
Phase 2: Oral revumenib; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows:
* Cohort 2A: Participants with KMT2Ar ALL/MPAL
* Cohort 2B: Participants with KMT2Ar AML
* Cohort 2C: Participants with NPM1m AML
revumenib
revumenib orally
cobicistat
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
Interventions
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revumenib
revumenib orally
cobicistat
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. Phase 1:
* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
* Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
* Arm C: Participants receiving revumenib in combination with cobicistat.
* Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor).
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
* Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
2. Phase 2:
Documented R/R active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the NCCN Guidelines® for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020).
* Cohort 2A: Documented R/R ALL/MPAL with KMT2A rearrangement.
* Cohort 2B: Documented R/R AML with KMT2A rearrangement.
* Cohort 2C: Documented R/R AML with NPM1m.
3. White blood cell count below 25,000/ microliter at time of enrollment. Participants may receive cytoreduction prior to enrollment per protocol-specified criteria.
4. Male or female participants aged ≥30 days old.
5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥50.
6. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 neuropathy or alopecia.
7. Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
8. Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion.
9. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T or NK cell therapy.
10. Antileukemia Therapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of antileukemic therapy.
11. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
12. Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent.
13. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing or cytoreductive therapy.
14. Adequate organ function.
15. If of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
Exclusion Criteria
1. Diagnosis of active acute promyelocytic leukemia.
2. Isolated extramedullary relapse (Phase 2 only).
3. Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic).
4. Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
5. Hepatitis B or C.
6. Pregnant or nursing women.
7. Cardiac Disease:
* Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
* Corrected QT interval (QTc) \>450 milliseconds.
8. Gastrointestinal Disease:
* any gastrointestinal issue of the upper GI tract that might affect oral drug absorption or ingestion (that is, gastric bypass, gastroparesis, etc).
* Cirrhosis with a Child-Pugh score of B or C.
9. Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD \>Grade 0 within 4 weeks of enrollment. All transplant participants must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy, or concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the participant is not receiving any systemic therapy or radiation.
11. In Phase 1 and Phase 2: Participants requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (for example, diphenhydramine, famotidine, ondansetron, Bactrim) and the azoles permitted in the relevant arms of Phase 1 and in Phase 2.
30 Days
ALL
No
Sponsors
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Syndax Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Angela R Smith, M.D.
Role: STUDY_DIRECTOR
Syndax Pharmaceuticals
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
University Of California Care Medical Group - Norris Comprehensive Cancer Center And Hospital
Los Angeles, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
University of Colorado
Aurora, Colorado, United States
Florida Cancer Specialists and Research Institute
Sarasota, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory Winship Cancer Institute
Atlanta, Georgia, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
The University of Chicago Medical Center
Chicago, Illinois, United States
University of Iowa hospital
Iowa City, Iowa, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Washington University in St. Louis School of Medicine
St Louis, Missouri, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Montefiore Medical Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
University of Cincinnati
Cincinnati, Ohio, United States
Ohio State University
Columbus, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Huntsman Cancer Institute at the University of Utah
Salt Lake City, Utah, United States
Peter MacCallum Cancer Centre (PMCC)
Melbourne, Victoria, Australia
Royal Melbourne Hospital (RMH)
Parkville, Victoria, Australia
Alfred Hospital
Melbourne, , Australia
Sir Charles Gairdner Hospital
Nedlands, , Australia
Royal North Shore Hospital
Saint Leonards, , Australia
University Health Network
Toronto, , Canada
The Hospital for Sick Children
Toronto, , Canada
Hospital Saint-Louis - APHP
Paris, , France
Centre Hospitalier Universitaire (CHU) de Bordeaux
Pessac, , France
Centre Hospitalier Lyon Sud
Pierre-Bénite, , France
Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP
Villejuif, , France
University Hospital Of Ulm, Universitatsklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
Universitaetsklinikum Essen (AoR)
Essen, , Germany
Universitaetsmedizin Greifswald
Greifswald, , Germany
Universitaetsmedizin Der Johannes
Gutenberg, , Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, , Germany
University of Leipzig
Leipzig, , Germany
Klinikum Nuernberg Nord
Nuremberg, , Germany
Rambam Health Care Campus (RHCC)
Haifa, , Israel
Shaare Zedek Medical Center
Jerusalem, , Israel
Hadassah Medical Center- Ein Kerem
Jerusalem, , Israel
Galilee Medical Center
Nahariya, , Israel
Rabin Medical Center
Petah Tikva, , Israel
Sheba Medical Center
Ramat Gan, , Israel
IRCCS Azienda Ospedaliero Universitaria di Bologna
Bologna, , Italy
Istituto Romagnolo Per Lo Studio dei tumori Dino Amadori
Meldola, , Italy
IRCCS-Istituto Europeo di Oncologia
Milan, , Italy
Universita Cattolica Fondazione Policlinico Agostino Gemelli
Roma, , Italy
S Bortolo Hospital AULSS 8 Berica
Vicenza, , Italy
Vilnius University Hospital Santaros Klinikos
Vilnius, , Lithuania
Princess Maxima Center for Pediatric Oncology
Utrecht, , Netherlands
Hospital Centro Comprensivo de Cancer UPR
San Juan, , Puerto Rico
Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals
L'Hospitalet de Llobregat, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, , Spain
Countries
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Central Contacts
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Facility Contacts
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Manjyot Nanhwan
Role: primary
Shirley Sian
Role: primary
Kyle Denzel Cobarrubias
Role: primary
Katelyn Anttila
Role: primary
Terri Peterson, RN
Role: primary
Shannon Gleason, MLS, CCRC
Role: primary
Howie Weiner, CCRP
Role: primary
Morgan Johnson
Role: primary
Lindsay Rae
Role: backup
Hannah Hartman
Role: primary
Madeline Stowe
Role: backup
Kait Tkachuk
Role: primary
Karen Fehn
Role: primary
Joel Victor
Role: backup
Linda Brown
Role: primary
Nadia Osman
Role: primary
Molly Brandenburg
Role: primary
OHSU Knight Cancer Institute Clinical Trials
Role: primary
Robin E Blauser, BSN RN
Role: primary
Ghayas Issa, MD
Role: primary
Farha Inam
Role: primary
Cathy Tran
Role: primary
Aiman Siddiqi
Role: primary
Karine Celli-Lebras
Role: primary
Thomas Grenier
Role: primary
Alexandre Deloire
Role: primary
Mathilde Petit
Role: primary
Julia Birken
Role: primary
Berit Riemer
Role: primary
Conny Schuck
Role: primary
Petra Kuehne
Role: primary
Jana Heinrichs-Knopf
Role: primary
Florian Schindler
Role: primary
Hadil Asadi
Role: primary
Dafna Laufer
Role: primary
Leah Greenfeld
Role: primary
Role: backup
Lana Saada
Role: primary
Contact: Sharon Hercman Dachevsky
Role: primary
Yuval Carmel
Role: primary
Francesco Ingletto
Role: primary
Federica Frabetti
Role: primary
Liliana Calabrese
Role: primary
Gulia De Santis
Role: primary
Irene Mutterle
Role: primary
Andrejus Cernovas
Role: primary
Secretary Trial and Data Centrum
Role: primary
Doris E. Cuadrado Landrau
Role: primary
Anna Valer
Role: primary
Laura More
Role: primary
Elisa Gonzales
Role: primary
References
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Arellano ML, Thirman MJ, DiPersio JF, Heiblig M, Stein EM, Schuh AC, Zucenka A, de Botton S, Grove CS, Mannis GN, Papayannidis C, Perl AE, Issa GC, Aldoss I, Bajel A, Dickens DS, Kuhn MWM, Mantzaris I, Raffoux E, Traer E, Amitai I, Dohner H, Greco C, Kovacsovics T, McMahon CM, Montesinos P, Pigneux A, Shami PJ, Stone RM, Wolach O, Harpel JG, Chudnovsky Y, Yu L, Bagley RG, Smith AR, Blachly JS. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood. 2025 Aug 28;146(9):1065-1077. doi: 10.1182/blood.2025028357.
Issa GC, Aldoss I, Thirman MJ, DiPersio J, Arellano M, Blachly JS, Mannis GN, Perl A, Dickens DS, McMahon CM, Traer E, Zwaan CM, Grove CS, Stone R, Shami PJ, Mantzaris I, Greenwood M, Shukla N, Cuglievan B, Kovacsovics T, Gu Y, Bagley RG, Madigan K, Chudnovsky Y, Nguyen HV, McNeer N, Stein EM. Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). J Clin Oncol. 2025 Jan;43(1):75-84. doi: 10.1200/JCO.24.00826. Epub 2024 Aug 9.
Issa GC, Aldoss I, DiPersio J, Cuglievan B, Stone R, Arellano M, Thirman MJ, Patel MR, Dickens DS, Shenoy S, Shukla N, Kantarjian H, Armstrong SA, Perner F, Perry JA, Rosen G, Bagley RG, Meyers ML, Ordentlich P, Gu Y, Kumar V, Smith S, McGeehan GM, Stein EM. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. 2023 Mar;615(7954):920-924. doi: 10.1038/s41586-023-05812-3. Epub 2023 Mar 15.
Sasca D, Guezguez B, Kuhn MWM. Next generation epigenetic modulators to target myeloid neoplasms. Curr Opin Hematol. 2021 Sep 1;28(5):356-363. doi: 10.1097/MOH.0000000000000673.
Jimenez JA, Apfelbaum AA, Hawkins AG, Svoboda LK, Kumar A, Ruiz RO, Garcia AX, Haarer E, Nwosu ZC, Bradin J, Purohit T, Chen D, Cierpicki T, Grembecka J, Lyssiotis CA, Lawlor ER. EWS-FLI1 and Menin Converge to Regulate ATF4 Activity in Ewing Sarcoma. Mol Cancer Res. 2021 Jul;19(7):1182-1195. doi: 10.1158/1541-7786.MCR-20-0679. Epub 2021 Mar 19.
Related Links
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Related Info
Related Info
Other Identifiers
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2020-004104-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
SNDX-5613-0700
Identifier Type: -
Identifier Source: org_study_id