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.
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)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
447
revumenib orally
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
RECRUITINGUniversity Of California Care Medical Group - Norris Comprehensive Cancer Center And Hospital
Los Angeles, California, United States
RECRUITINGStanford Cancer Institute
Palo Alto, California, United States
RECRUITINGUniversity of Colorado
Aurora, Colorado, United States
Number of participants with dose-limiting toxicities (DLTs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Time frame: Approximately 1 year
Number of participants with treatment-emergent adverse events (TEAEs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Time frame: Approximately 1 year
Cmax (Phase 1)
Maximum plasma concentration (Cmax) of revumenib and relevant metabolites (Phase 1)
Time frame: Approximately 1 year
Tmax (Phase 1)
Time to observed maximum plasma concentration of revumenib and relevant metabolites (Phase 1)
Time frame: Approximately 1 year
AUC0-t (Phase 1)
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of revumenib and relevant metabolites (Phase 1)
Time frame: Approximately 1 year
CR+CRh rate (Phase 2 [Cohorts 2A-2C])
To assess the complete remission (CR) and complete remission with partial hematologic recovery (CRh) rate (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
Number of participants with TEAEs (Phase 2 [Cohorts 2A-2C])
Assessed by the NCI CTCAE version 5.0 (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
Cmax (Phase 2 [Cohort 2D])
Cmax of revumenib (Phase 2 \[Cohort 2D\])
Time frame: Approximately 3 years
AUC0-tau (Phase 2 [Cohort 2D])
Area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC0-tau) of revumenib (Phase 2 \[Cohort 2D\])
Time frame: Approximately 3 years
Transfusion independence (Phase 2 [Cohorts 2A-2C])
Transfusion independence is defined as any transfusion-free period lasting for at least 56 consecutive days
Time frame: Approximately 3 years
CRc rate (Phase 2 [Cohorts 2A-2C])
To assess the composite definition of complete remission (CRc) rate (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
ORR (CRc+ morphological leukemia-free state [MLFS] + partial remission [PR]) (Phase 2 [Cohorts 2A-2C])
To assess the overall response rate (ORR) of revumenib (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
TTR (Phase 2 [Cohorts 2A-2C])
To assess the time to response (TTR) of revumenib (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 34 months
DOR (Phase 2 [Cohorts 2A-2C])
To assess the duration of response (DOR) of revumenib (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
EFS (Phase 2 [Cohorts 2A-2C])
To assess the event free survival (EFS) of revumenib (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
OS (Phase 2 [Cohorts 2A-2C])
To assess overall survival (OS) of revumenib (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 5 years
Cmax (Phase 2 [Cohorts 2A-2C])
Cmax of revumenib and relevant metabolites (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
Tmax (Phase 2 [Cohorts 2A-2C])
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Florida Cancer Specialists and Research Institute
Sarasota, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
COMPLETEDEmory Winship Cancer Institute
Atlanta, Georgia, United States
RECRUITINGChildren's Healthcare of Atlanta
Atlanta, Georgia, United States
COMPLETEDThe University of Chicago Medical Center
Chicago, Illinois, United States
RECRUITINGUniversity of Iowa hospital
Iowa City, Iowa, United States
RECRUITING...and 47 more locations
Tmax of revumenib and relevant metabolites (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
AUC0-t (Phase 2 [Cohorts 2A-2C])
AUC0-t of revumenib and relevant metabolites (Phase 2 \[Cohorts 2A-2C\])
Time frame: Approximately 3 years
Number of participants with TEAEs (Phase 2 [Cohort 2D])
Assessed by the NCI CTCAE version 5.0 (Phase 2 \[Cohort 2D\]))
Time frame: Approximately 3 years