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Revumenib treatment for relapsed/refractory leukemias with specific genetic mutations

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

Phase1; Phase2 Interventional Syndax Pharmaceuticals · NCT04065399

This study is testing a new drug called revumenib to see if it can help people with certain types of relapsed or hard-to-treat leukemias that have specific genetic changes.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment447 (estimated)
Ages30 Days and up
SexAll
SponsorSyndax Pharmaceuticals Industry-sponsored
Drugs / interventionschimeric antigen receptor, chemotherapy, Immunotherapy, Radiation, prednisone
Locations57 sites (Duarte, California and 56 other locations)
Trial IDNCT04065399 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of revumenib in patients with relapsed or refractory leukemias, particularly those with MLL/KMT2A gene rearrangements or NPM1 mutations. The study consists of a Phase 1 dose escalation to determine the maximum tolerated dose and a Phase 2 expansion to assess the drug's effectiveness and safety across specific leukemia subtypes. Participants will be assigned to different arms based on their concurrent medications and genetic profiles. The trial aims to provide a targeted treatment approach for acute leukemias.

Who should consider this trial

Good fit: Ideal candidates include individuals with active acute leukemia and specific genetic mutations or rearrangements.

Not a fit: Patients without active disease or those not harboring the targeted genetic mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with difficult-to-treat leukemias.

How similar studies have performed: Other studies have shown promise with targeted therapies in leukemia, suggesting potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Duarte, California and 56 other locations

+7 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Acute Myeloid LeukemiaAcute Lymphoblastic LeukemiaMixed Lineage Acute LeukemiaMixed Phenotype Acute LeukemiaAcute Leukemia of Ambiguous LineageAMLALLMPAL
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.