A Study of Ruxolitinib in Combination With Ulixertinib in People With Myelofibrosis

NCT06773195 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 24-157
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 9

Brief Summary

The researchers are doing this study to find out whether the combination of ruxolitinib and ulixertinib is a safe and effective treatment for people with myelofibrosis. The researchers will test different doses of ulixertinib to find the highest dose that causes few or mild side effects in participants when given in combination with ruxolitinib.

Conditions

Myelofibrosis

Keywords

post-ET myelofibrosis; post-PV myelofibrosis,; post-pre-fibrotic myelofibrosis; JAK/MEK inhibition; Ruxolitinib; Ulixertinib

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity evaluable participants

  If none of the initial 3 patients in a cohort experience a dose limiting toxicity (DLT), then the next dose level will be studied in another cohort of 3 patients. If 1 of the initial 3 patients at a given dose level experience a DLT, up to 3 additional patients will be treated at that same dose level. Escalation will continue if not more than 1 of the 6 patients experience a DLT.

  up to 28 days

• Response to therapy

  as defined by International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT working criteria)

  at week 25

Study Arms (1)

JAK/MEK inhibition with Ruxolitinib and Ulixertinib

EXPERIMENTAL

Phase 1: There are 3 planned dose levels of ulixertinib (450 mg BID, 300 mg BID, or 150 mg BID) in combination with ruxolitinib for 28 day cycles. A 3+3 dose escalation design will be used to determine the RP2D of ulixertinib with ruxolitinib. Phase 2: Participants will be treated with ulixertinib at the RP2D determined from the phase 1 part of the study in combination with ruxolitinib for 28 day cycles.

Drug: Ulixertinib; Drug: Ruxolitinib

Interventions

Ulixertinib DRUG

There are 3 planned dose levels of ulixertinib(450 mg BID, 300 mg BID, or 150 mg BID)

JAK/MEK inhibition with Ruxolitinib and Ulixertinib

Ruxolitinib DRUG

Ruxolitinib for 28 day cycles.

JAK/MEK inhibition with Ruxolitinib and Ulixertinib

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of primary myelofibrosis, post-ET myelofibrosis, post-PV myelofibrosis, or post-pre-fibrotic myelofibrosis by WHO 2016 criteria.
• Age ≥18 years.
• Receiving ruxolitinib monotherapy for at least 3 months with stable dose (10 mg BID to 20mg BID) for at least 4 weeks before first dose of study drug. Note: stable ruxolitinib dosing should be achieved according to strict adherence to dose modification/reduction guidelines detailed in the ruxolitinib package insert, for patients with renal impairment, and/or hepatic impairment.
• Must have DIPSS+ intermediate 2 or greater risk disease, or MIPSS70+ intermediate or greater risk disease
• Persistent disease despite ruxolitinib monotherapy, as demonstrated by:
• o Grade 2 or 3 reticulin/collagen fibrosis on bone marrow AND
• Splenomegaly (palpable at least 5cm below subcostal margin/or spleen volume \> 450cm\^3) OR
• Active symptoms (MPN-SAF TSS score \>10 with at least one MPNSAF TSS score \>5 or two scores \>3) OR
• ECOG performance status ≤2
• Participants must have adequate organ and marrow function as defined below unless the elevated laboratory values are attributable to Gilbert's Syndrome with Sponsor review and approval:
• Absolute neutrophil count ≥ 0.5 K/mcL
• Platelets ≥ 50 K/mcL
• Direct bilirubin ≤ 1.5 times institutional upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times institutional upper limit of normal (ULN
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN

You may not qualify if:

• Use of experimental drug therapy for MF or any other standard drug with the exception of hydroxyurea or ruxolitinib within 2 weeks of starting combination therapy and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better. Hydroxyurea may be utilized to control leukocytosis for up to 4 weeks during study
• Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Unwilling to receive red blood cell transfusion to treat low hemoglobin.
• Participants who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib and ulixertinib.
• Participants requiring any medications or substances that are strong inhibitors or inducers of 3A4, strong inhibitors of CYP1A2 and CYP2D6, and inhibitors of Pglycoprotein (P-gp). Strong inhibitors or inducers of 3A4, strong inhibitors of CYP1A2 and CYP2D6, and inhibitors of P-gp must be stopped within 14 days (or 5 half-lives) of study commencement. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Participants who are pregnant or breastfeeding.
• Pregnant women are excluded from this study because ruxolitinib and ulixertinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib and ulixertinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib and ulixertinib.
• Active bacterial, fungal, or viral infection requiring treatment.
• Participants with chronic Human immunodeficiency virus (HIV) or hepatitis B or C viral infection.
• HIV-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: testing does not have to be performed during screening unless participant has known or suspected history of HIV.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Presence of active interstitial lung disease or pneumonitis.
• History of cardiovascular risk factors:
• Clinically significant, uncontrolled arrythmias and/or conduction abnormalities. Participants with controlled atrial fibrillation \>30 days prior to study initiation are eligible.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• BioMed Valley Discoveries, Inc: collaborator
• Incyte Corporation: collaborator

Study Sites (9)

Massachusetts General Hospital (Data Collection Only)

Boston, Massachusetts, 02114, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited 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

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ulixertinib; ruxolitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Raajit Rampal, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raajit Rampal, MD, PhD

CONTACT

646-608-3746; rampalr@mskcc.org

Prioty Islam, MD, MS

CONTACT

646-608-4273

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: January 14, 2025
• Study Start: January 7, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (9)