RecruitingPhase 1 / Phase 2

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
30 Days and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests revumenib for acute leukemia, a fast-growing blood cancer, including leukemia that came back or did not respond to treatment. It aims to find a safe dose and learn how well the drug works. Some study groups require certain gene changes in the leukemia cells.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have active acute leukemia or leukemia with certain gene changes that can still be found in the bone marrow. Some groups allow very small amounts of disease or disease only outside the bone marrow.
  • For Phase 2, have leukemia that came back or did not respond to treatment. Each group has rules about leukemia type and gene changes, such as KMT2A, NPM1, or NUP98.
  • Be at least 30 days old. People taking revumenib with cobicistat must weigh at least 35 kg. Group 2D requires age 18 or older and weight of at least 40 kg.
  • Have a white blood cell count below 25,000 per microliter. Treatment to lower this count may be allowed before joining.
  • Meet the study’s rules for daily activity and organ health. Most side effects from past treatment must be mild or gone; exceptions apply for nerve damage and hair loss.
  • Meet the waiting periods after past cancer treatments or a stem cell transplant. These periods depend on the treatment and study group.
  • Meet your study group’s medicine rules. Phase 1 groups have different rules for medicines that change how the body breaks down revumenib.
  • If able to become pregnant, agree to use highly effective birth control during the study and for 120 days after the last dose.

Who can't join

  • Have active acute promyelocytic leukemia, a specific leukemia type, or active disease in the brain or spinal cord. In Phase 2 groups 2A–2C, relapse only outside the bone marrow is also excluded.
  • Have a detectable amount of HIV in the blood within the past 6 months, or have hepatitis B or C.
  • Are pregnant or breastfeeding.
  • Have certain serious heart problems, a stroke, or a mini-stroke within the past 6 months, or a heart rhythm test called QTc above 450 milliseconds.
  • Have an upper digestive tract problem that could affect swallowing or absorbing the drug, or moderate to severe liver scarring.
  • Have signs of graft-versus-host disease, where donor cells attack the body, within the past 4 weeks. Transplant patients must also be off certain immune-suppressing medicines for at least 4 weeks, with limited steroid exceptions.
  • Have another cancer within the past 2 years, except certain treated early cancers or a slow-growing lymphoma that meets the study’s rules.
  • Need medicines that may cause certain heart rhythm changes, except medicines specifically allowed by the study.

Simplified for readability. The official criteria below are what the study team uses.

Official 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.

Study sites (22)

CA

CO

FL

GA

IA

IL

MA

MO

NC

NJ

NY

OH

OR

PA

TX

UT