Revumenib in Patients With Myelofibrosis

NCT07734077 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY-26-008645P01CA108671
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib/II 2 study investigating the safety and efficacy of revumenib in two cohorts of participants with myelofibrosis. COHORT-1 will investigate the safety of revumenib as monotherapy in participants with myelofibrosis previously treated with a JAK inhibitor. Following confirmation of safety in COHORT-1, the study will proceed with enrollment in COHORT-2, which will evaluate the efficacy and safety of revumenib in combination with a JAK inhibitor.

Conditions

Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis

Keywords

Myelofibrosis; Revumenib; JAK inhibitor

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT)

  (COHORT-1) Dose limiting toxicity (DLT) defined as according to the NCI CTCAE v6. AEs attributable to the study agents (possibly / probably / definitely related) will count towards the toxicity stopping boundaries. These include, but not limited to, neutrophil count decreased, thrombocytopenia, and other non-hematologic AEs

  2 months

• Number of Treatment related adverse events (AEs)

  (COHORT-1) Number of treatment specific adverse events (AEs) by CTCAE v6.0 (COHORT-2) during dose escalation phase

  6 months

• Overall response rate (ORR) for COHORT-2

  (COHORT-2) Overall response rate (ORR) defined as CR, PR, or CI by the revised IWG-MRT and ELN criteria after 6 cycles of therapy (each cycle is one month.)

  6 months

Secondary Outcomes (6)

• Overall response rate (ORR) for COHORT 1

  6 months

• Number of treatment related grade ≥ 3 AEs

  6 months

• Proportion of participants achieving CI

  3 months and 6 months

• Change in spleen volume

  3 months and 6 months

• Participants achieving anemia response

  6 months

Study Arms (2)

COHORT-1 (revumenib monotherapy)

EXPERIMENTAL

Revumenib monotherapy utilizing a 3+3 dose-escalation design

Drug: Revumenib

COHORT-2 (revumenib added to JAK inhibitor therapy)

EXPERIMENTAL

Dosage of revumenib from Cohort 1 plus JAK inhibitor therapy (ruxolitinib, fedratinib, or momelotinib)

Drug: Revumenib; Drug: Ruxolitinib; Drug: FEDRATINIB; Drug: Momelotinib

Interventions

Revumenib DRUG

Dose Level 1: Revumenib 160mg twice daily or 110mg twice daily Dose Level 2: Revumenib 270mg twice daily or 160mg twice daily

Also known as: Revuforj)

COHORT-1 (revumenib monotherapy); COHORT-2 (revumenib added to JAK inhibitor therapy)

Ruxolitinib DRUG

Part of routine care. Participants to continue on dosage as prescribed by provider, 5 to 20 mg BID

COHORT-2 (revumenib added to JAK inhibitor therapy)

FEDRATINIB DRUG

Part of routine care. Participants to continue on dosage as prescribed by provider, 100 mg to 400 mg daily.

COHORT-2 (revumenib added to JAK inhibitor therapy)

Momelotinib DRUG

Part of routine care. Participants to continue on dosage as prescribed by provider, 100 mg to 200 mg daily.

COHORT-2 (revumenib added to JAK inhibitor therapy)

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Adults ≥ 18 years of age at time of signing the informed consent
• Participants must voluntarily sign informed consent form (ICF) and be willing and able to adhere to the study visit schedule and all protocol requirements.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Participants must have a pathologically confirmed diagnosis of PMF, post-ET-MF or post-PV-MF as per the WHO diagnostic criteria, with intermediate-1 or higher risk disease by DIPSS (14.1).
• Criteria for COHORT-1 (Monotherapy): Treated with at least one prior line of JAK inhibitor therapy to which they were refractory/resistant, lost response, or intolerant, or is not a candidate for approved JAK inhibitor therapy per investigator judgement, and with one or more of the following features of active disease:
• Spleen palpable ≥ 5 cm below the left costal margin or \> 450cm3 by MRI/CT
• MPN-SAF TSS ≥ 10
• Transfusion dependence (requiring at least 6 units of PRBCs in the 12 weeks prior to study enrollment, for a hemoglobin \< 8.5g/dL in the absence of bleeding or treatment-induced anemia)
• Criteria for COHORT-2 (Combination therapy): Currently receiving treatment with an approved JAK inhibitor (including ruxolitinib, fedratinib, or momelotinib) with stable dose for at least 12 weeks prior to study enrollment, and with one or more of the following features of active disease:
• Spleen palpable ≥ 5 cm below the left costal margin or \> 450cm3 by MRI/CT
• MPN-SAF TSS ≥ 10
• Transfusion dependence (requiring at least 6 units of PRBCs in the 12 weeks prior to study enrollment, for a hemoglobin \< 8.5g/dL in the absence of bleeding or treatment-induced anemia)
• Adequate organ function as demonstrated by the following within 28 days prior to Cycle 1 Day 1:
• ALT (SGPT) and/or AST (SGOT) \< 3 × the upper limit of normal (ULN), or \< 5 × ULN if, upon judgment of the treating physician, it is believed to be due to MF-related extramedullary hematopoiesis (EMH);

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Treatment with any MF-directed therapy (including investigational therapies) within 2 weeks or 5 half-lives, whichever is shorter, of Cycle 1 Day 1
• Participants in COHORT-1 should not have received a JAK inhibitor within 14 days prior to Cycle 1 Day 1. Participants who remain on JAK inhibitor at time of screening should be tapered off per investigator discretion.
• Hydroxyurea is permitted until the day prior to C1D1, if needed for disease control.
• Undergone allogeneic hematopoietic stem cell transplant (allo-HSCT) within the last 6 months prior to enrollment, or with active GVHD and/or on immunosuppressive therapy.
• Not currently a candidate for allo-HSCT, per investigator discretion. Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible.
• Prior splenectomy, splenic irradiation, or splenic artery embolization within 6 months of C1D1
• GI disease meeting any of the following criteria:
• Impairment of GI function that could significantly alter the absorption of revumenib (eg. Gastric bypass, gastroparesis)
• Cirrhosis with a Child-Pugh score of B or C, or National Cancer Institute (NCI) Organ Dysfunction Working Group category of Severe Dysfunction
• Inability to swallow oral medications
• Any of the following cardiac abnormalities:
• Any of the following within the 6 months before study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident or transient ischemic attack. Participants with controlled atrial fibrillation are allowed to enroll
• QTcF (Fridericia's correction) \> 450ms at screening
• Diagnosis of suspicion of Long QT syndrome or family history of Long QT syndrome

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• John Mascarenhas: lead
• Syndax Pharmaceuticals: collaborator

Study Sites (1)

Icahn School of Medicine at the Mount Sinai Hospital

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

revumenib; ruxolitinib; fedratinib; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Anthony M Hunter, MD

  Emory University

  STUDY CHAIR

Central Study Contacts

Gillian Sanchez

CONTACT

(212) 241-1391; gillian.sanchez@mssm.edu

Shakira Forde

CONTACT

shakira.forde@mssm.edu

Study Design

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

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)