RECRUITING
Phase 1 / Phase 2
ClinicalTrials.gov
A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation
Sponsor: Syndax Pharmaceuticals • ClinicalTrials.gov ID: NCT04065399
Registry updated: 2026-10-09
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Check Eligibility →Description
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.
Interventions
-
revumenib
(Drug)
revumenib orally
-
cobicistat
(Drug)
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
Eligibility criteria
Key Inclusion Criteria:
Participants must have active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020), or acute leukemia harboring KMT2A rearrangement, NUP98 rearrangement, or NPM1 mutation that have detectable disease in the bone marrow.
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.
* Cohort 2D: Documented R/R acute leukemia with a genetic mutation expected to lead to HOX/MEIS upregulation (for example, KMT2Ar, NPM1m, and NUP98r), including participants who are MRD-positive by multiparametric flow cytometry or molecular methods only, and including participants with isolated extramedullary disease.
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. Participants intended to receive SNDX-5613 in combination with cobicistat must weigh ≥35 kilograms (kg). Participants in Cohort 2D must be ≥18 years of age and have a body weight ≥40 kg.
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.
Phase 1 and Phase 2 Cohorts 2A-2C only:
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.
Phase 2 Cohort 2D only:
At least 14 days since any other investigational or commercially available antileukemic therapy, with the following exceptions:
1. Cytoreductive therapy with hydroxyurea, low-dose cytarabine (20 mg/square meter (m\^2)/day subcutaneously \[SC\] for 10 days) or low-dose etoposide (up to 200 mg/day orally for 10 days) may be administered concurrently with SNDX-5613.
2. Intrathecal chemotherapy for CNS prophylaxis is permitted at the treating physician's discretion.
3. Steroids at physiologic dosing (equivalent to ≤10 mg prednisone daily for participants ≥18 years or ≤10 mg/m\^2/day for participants \<18 years) or for cytoreductive therapy.
14. Adequate organ function.
15. If of childbearing potential, willing to use a highly effective method of contraception from the time of enrollment through 120 days following the last study drug dose.
Key Exclusion Criteria:
Participants meeting any of the following criteria are not eligible for study participation:
1. Diagnosis of active acute promyelocytic leukemia.
2. Isolated extramedullary relapse (Phase 2 Cohorts 2A-2C 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 and gastroparesis).
* 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.
Note: Other protocol defined inclusion/exclusion criteria may apply.
Conditions
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Mixed Lineage Acute Leukemia
Mixed Phenotype Acute Leukemia
Acute Leukemia of Ambiguous Lineage
Locations
- 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
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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.
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