A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation
Start Date
11/5/2019
Completion Date
12/15/2027
Summary
Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia. In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.
Detailed Description
Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in one of six dose-escalation arms: 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 4 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 * Cohort 2D: Participants with acute leukemia (including KMT2Ar, NPM1m, NUP98r and other acute leukemias expected to have HOX/MEIS upregulation)
Eligibility Criteria
Age Range: No minimum to No maximum
Interventions
revumenib
cobicistat
Conditions
Locations
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
University Of California Care Medical Group - Norris Comprehensive Cancer Center And Hospital
Los Angeles, California 90033
United States
Stanford Cancer Institute
Palo Alto, California 94305
United States
University of Colorado
Aurora, Colorado 80045
United States
Florida Cancer Specialists and Research Institute
Sarasota, Florida 34232
United States
Moffitt Cancer Center
Tampa, Florida 33162
United States
Emory Winship Cancer Institute
Atlanta, Georgia 30322
United States
Children's Healthcare of Atlanta
Atlanta, Georgia 30329
United States
The University of Chicago Medical Center
Chicago, Illinois 60637
United States
University of Iowa Hospital
Iowa City, Iowa 52246
United States
Dana Farber Cancer Institute
Boston, Massachusetts 02215
United States
Washington University in St. Louis School of Medicine
St Louis, Missouri 63110
United States
Hackensack University Medical Center
Hackensack, New Jersey 07601
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Montefiore Medical Center
New York, New York 10467
United States
Duke University Medical Center
Durham, North Carolina 27110
United States
University of Cincinnati
Cincinnati, Ohio 45267
United States
Ohio State University
Columbus, Ohio 43201
United States
Oregon Health & Science University
Portland, Oregon 97239
United States
University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Huntsman Cancer Institute at the University of Utah
Salt Lake City, Utah 84112
United States
Peter MacCallum Cancer Centre (PMCC)
Melbourne, Victoria 3000
Australia
Royal Melbourne Hospital (RMH)
Parkville, Victoria 3050
Australia
Alfred Hospital
Melbourne, 3004
Australia
Sir Charles Gairdner Hospital
Nedlands, 6009
Australia
Royal North Shore Hospital
Saint Leonards, 2065
Australia
University Health Network
Toronto, M5G 2M9
Canada
The Hospital for Sick Children
Toronto,
Canada
Hospital Saint-Louis - APHP
Paris, 75010
France
Centre Hospitalier Universitaire (CHU) de Bordeaux
Pessac, 33604
France
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
France
Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP
Villejuif, 94805
France
University Hospital Of Ulm, Universitatsklinikum Ulm
Ulm, Baden-Wurttemberg 89081
Germany
Universitaetsklinikum Essen (AoR)
Essen, 45147
Germany
Universitaetsmedizin Greifswald
Greifswald, 17475
Germany
Universitaetsmedizin Der Johannes
Gutenberg, 55131
Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
Germany
University of Leipzig
Leipzig, 04103
Germany
Klinikum Nuernberg Nord
Nuremberg, 90419
Germany
Rambam Health Care Campus (RHCC)
Haifa, 3109601
Israel
Shaare Zedek Medical Center
Jerusalem, 9103102
Israel
Hadassah Medical Center- Ein Kerem
Jerusalem, 9112001
Israel
Galilee Medical Center
Nahariya, 2210010
Israel
Rabin Medical Center
Petah Tikva, 4941492
Israel
Sheba Medical Center
Ramat Gan, 52621
Israel
IRCCS Azienda Ospedaliero Universitaria di Bologna
Bologna, 40138
Italy
Istituto Romagnolo Per Lo Studio dei tumori Dino Amadori
Meldola, 47014
Italy
IRCCS-Istituto Europeo di Oncologia
Milan, 20141
Italy
Universita Cattolica Fondazione Policlinico Agostino Gemelli
Roma, 00168
Italy
S Bortolo Hospital AULSS 8 Berica
Vicenza, 36100
Italy
Vilnius University Hospital Santaros Klinikos
Vilnius, 08661
Lithuania
Princess Maxima Center for Pediatric Oncology
Utrecht, 3584 CS
Netherlands
Hospital Centro Comprensivo de Cancer UPR
San Juan, 00935
Puerto Rico
Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08908
Spain
Hospital Universitario Virgen del Rocio
Seville, 41013
Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Spain