A Study of Revumenib and Mezigdomide in People With Leukemia

NCT07356154 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-229
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to find out whether the combination of mezigdomide and revumenib is a safe treatment for people with relapsed or refractory KMT2A-r, NUP98-r, and NPM1-m acute leukemias.

Conditions

Leukemia; Acute Leukemia; Relapse Leukemia; Refractory Leukemia; Refractory Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia

Keywords

Leukemia; Acute Leukemia; Relapse Leukemia; Refractory Leukemia; Refractory Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia; Memorial Sloan Kettering Cancer Center; 25-229

Outcome Measures

Primary Outcomes (1)

• Phase I: Maximum Tolerated Dose

  Maximum Tolerated Dose/MTD is defined as the highest dose level in which 6 participantshave been treated with at most 1 instance of dose limiting toxicities/DLT.

  1 year

Study Arms (5)

Phase 1A

EXPERIMENTAL

The first cohort of 3 patients will be treated at dose level 1A

Drug: Revumenib; Drug: Mezigdomide

Phase 1B

EXPERIMENTAL

The next cohort of patients will not be treated until toxicity has been evaluated in the current cohort of patients.

Drug: Revumenib; Drug: Mezigdomide

Phase 1C

EXPERIMENTAL

The next cohort of patients will not be treated until toxicity has been evaluated in the current cohort of patients.

Drug: Revumenib; Drug: Mezigdomide

Phase 2: Menin Inhibitor Naive Cohort

EXPERIMENTAL

In the menin-inhibitor naïve cohort, there will be up to 24 patients, including up to 6 patients from the phase I portion of the study

Drug: Revumenib; Drug: Mezigdomide

Phase 2: Menin Inhibitor Exposed Cohort

EXPERIMENTAL

In the menin-inhibitor exposed cohort, there will be up to 16 patients, including up to 6 patients from the phase I portion of the study

Drug: Revumenib; Drug: Mezigdomide

Interventions

Revumenib DRUG

Revumenib is a novel menin inhibitor

Also known as: SNDX-5613

Phase 1A; Phase 1B; Phase 1C; Phase 2: Menin Inhibitor Exposed Cohort; Phase 2: Menin Inhibitor Naive Cohort

Mezigdomide DRUG

Mezigdomide (CC-92480) is an investigational CELMoD.

Also known as: CC-92480

Phase 1A; Phase 1B; Phase 1C; Phase 2: Menin Inhibitor Exposed Cohort; Phase 2: Menin Inhibitor Naive Cohort

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 12 years of age at the time of signing the informed consent form (ICF).
• Participant must weigh at least 40 kg
• Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
• Participant has relapsed/refractory acute leukemia defined acute myeloid leukemia, acute lymphoblastic leukemia, or mixed phenotype acute leukemia after as failure of at least 1 prior line of therapy (can be either primary refractory disease or progression during or after treatment)
• Participant has confirmed acute leukemia with detectable NPM1c, KMT2A translocation, or NUP98 translocation.
• At MSK, NPM1 testing utilizes MSK-REACT, a rapid multi-gene NGS panel used in all new AML diagnoses that is clinically validated by the Laboratory of Diagnostic Molecular Pathology pursuant to the requirements of CLIA'88 and approved by New York State, or MSK-IMPACT, a multi-gene NGS panel, which is authorized by the FDA. At non-MSK sites, NPM1 testing may be performed in local CLIA-certified laboratories using validated clinical assays with capable of detecting NPM1c variants at a frequency of ≥5%. Eligible patients must have an NPM1c (nucleophosmin) exon 12 variant as determined by these assays.
• At MSK, KMT2A and NUP98 testing will utilize chromosomal analysis and fluorescence in situ hybridization studies. At non-MSK sites, testing may be performed in local CLIA-certified laboratories using validated clinical assays with performance characteristics sufficient to detect relevant translocations. Eligible patients must have a KMT2A or NUP98 translocation as determined by these assays
• The patient's chart will be utilized for screening purposes
• Regarding prior treatment with a menin inhibitor:
• Participants enrolled in Phase 1 have no requirements regarding prior treatment with a menin inhibitor
• Participants enrolled in Phase 2, cohort 1, are required to be menin inhibitor naïve (no previous treatment with a menin inhibitor)
• Participants enrolled in Phase 2, cohort 2, are required to be menin inhibitor exposed (previous treatment received a menin inhibitor)
• Regarding prior alloSCT, at 60 days must have elapsed from day of transplant and at least 4 weeks must have elapsed from first dose of donor lymphocyte infusion.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 (if aged ≥18 years); Karnofsky Performance Scale of ≥50 (if aged ≥16 years and \<18 years); Lansky Performance Score of ≥50 (if aged \<16 years).
• Participant must have a WBC count \<25,000/μL at the time of initiation of study drug (leukapheresis may be performed and/or hydroxyurea may be administered to decrease the WBC count to \<25,000/μL).

You may not qualify if:

• Participants with acute promyelocytic leukemia
• Participants with isolated myeloid sarcoma
• Participants who have previously received mezigdomide.
• Participants with immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, disseminated intravascular coagulation, or uncontrolled tumor lysis syndrome.
• Participant has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the treating investigator, would make the patient inappropriate for entry into the study.
• Participants with concurrent other malignancy that will confound interpretation of study endpoints.
• Participants who have received other anti-leukemia therapy within 5 half-lives of the agent or 14 days, whichever is sooner, prior to study treatment and if toxicity related to said agent has not resolved; exceptions of acceptable concomitant therapies are listed below
• Concomitant cytoreductive therapy in the form of hydroxyurea, corticosteroids, or cytarabine is permitted.
• Concomitant therapy in the form of intrathecal chemotherapy for CNS treatment, is permitted.
• Radiation therapy is not permitted except for localized palliative radiation to focal lesions after discussion with the Medical Monitor for patients who have progressed but remain on the study due to perceived clinical benefit per Investigator assessment
• Participant has significant active cardiac disease within 6 months prior to start of study treatment, including New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke.
• Participant has QTc interval (i.e., Fridericia's correction \[QTcF\]) ≥ 450 ms (mean of triplicate ECG) or other factors that increase the risk of QT prolongation or ventricular arrhythmic events (e.g., family history of long QT interval syndrome). Patients with a QTcF over 450 ms due to a bundle branch block or a pacemaker may participate in the study with approval of the study principal investigator.
• Participant has active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Participant is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (10)

City of Hope Cancer Center (Data collection only)

Duarte, California, 91010, United States

NOT YET RECRUITING

Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Rockville Centre, New York, 11553, United States

RECRUITING

University of North Carolina (Data Collection Only)

Chapel Hill, North Carolina, 27514, United States

NOT YET RECRUITING

MD Anderson Cancer Center (Data Collection Only)

Houston, Texas, 77030, United States

NOT YET RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute

Interventions

revumenib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Eytan Stein, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eytan Stein, MD

CONTACT

646-608-3749; SteinE@mskcc.org

Neerav Shukla, MD

CONTACT

212-639-5158; shuklan@MSKCC.ORG

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: January 21, 2026
• Study Start: January 16, 2026
• Primary Completion (Estimated): January 16, 2029
• Study Completion (Estimated): January 16, 2029
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (10)