Comparing Momelotinib and Ruxolitinib in People With Untreated Myelofibrosis and Low Blood Cell Counts

NCT07498205 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 26CTP.LEUK02
• Study Type: interventional
• Target: 268
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to compare momelotinib and ruxolitinib as treatments for myelofibrosis with low blood cell counts. Both drugs are approved by the FDA to treat myelofibrosis. The study asks which drug does a better job at shrinking the spleen.

Conditions

Myelofibrosis; Myelofibrosis (MF)

Keywords

Myelofibrosis; momelotinib; ruxolitinib

Outcome Measures

Primary Outcomes (1)

• To estimate and compare the proportion of participants achieving a dual response [SVR35] and transfusion independence response from red blood cell transfusions.

  To estimate and compare the proportion of patients achieving a dual response both spleen response \[SVR35\] and transfusion independence response \[TI-R\] from red blood cell transfusions at week 24 post-Step 1 randomization in JAK-inhibitor naïve participants with myelofibrosis treated with momelotinib versus ruxolitinib.

  24 weeks after randomization

Secondary Outcomes (14)

• TI-R Rate

  24 weeks after Step 1 Randomization

• SVR35 at week 24 post-randomization

  24 weeks after Step 1 Randomization

• OS

  96 weeks after Step 1 Randomization

• PFS

  96 weeks after Step 1 Randomization

• SVR35 at week 24 post-randomization

  24 weeks after Step 1 Randomization

Other Outcomes (5)

• Symptom Burden

  96 weeks after Step 1 Randomization

• MF-SAF Scores

  96 weeks after Step 1 Randomization

• FACT-An Scores

  96 weeks after Step 1 Randomization

Study Arms (2)

Momelotinib

ACTIVE COMPARATOR

Momelotinib

Drug: Momelotinib

Ruxolitinib

ACTIVE COMPARATOR

Ruxolitinib

Drug: Ruxolitinib

Interventions

Momelotinib DRUG

200 mg daily x 96 weeks.

Also known as: JAK-inihibitor

Momelotinib

Ruxolitinib DRUG

Twice daily per treating investigator discretion not to exceed protocol specified guidelines.

Also known as: JAK-inihibitor

Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• Participants must have confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (PV) MF or post-essential thrombocythemia (ET) MF as assessed by the treating physician per 2022 WHO classification, and confirmed by a bone marrow biopsy within four years.
• Participants must have a spleen measuring ≥ 450 cm3 by MRI within 14 days prior to Step 1 registration. For participants with a medical contraindication to MRI or if MRI is unavailable, a CT scan may be performed.
• Participants must have DIPSS risk category of Intermediate-1, Intermediate-2 or High per Dynamic International Prognostic Scoring System (DIPSS) for MF.
• Participants must have blasts \<10% in peripheral blood within 28 days of Step 1 registration. If bone marrow biopsy performed within 28 days prior to Step 1 registration blasts must be \<10% as well.
• Participants must have discontinued all drugs used to treat MF, including hydroxyurea, peginterferon alfa-2a, ropeginterferon alfa-2b, anagrelide or busulfan ≥ 14 days prior to Step 1 registration.
• Participants must be ≥ 18 years old at the time of registration.
• Participants must have Zubrod/ECOG Performance Status of 0-2.
• Participants must have a complete medical history and physical exam within 28 days prior to Step 1 registration.
• Participants must meet hematologic parameters within 28 days prior to Step 1 registration.
• Participants must have a calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to Step 1 registration. For creatinine clearance formula see the tools on the CRA Workbench https://txwb.crab.org/TXWB/Tools.aspx.
• Participants must be able to take orally administered medication and comply with the oral regimen.
• Participants with a history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at Step 1 registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to Step 1 registration.
• Participants with a history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to Step 1 registration, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to Step 1 registration, if indicated.
• Participants must be offered the opportunity to participate in specimen banking.

You may not qualify if:

• Participants must have discontinued all drugs used to treat MF, including hydroxyurea, peginterferon alfa-2a, ropeginterferon alfa-2b, anagrelide or busulfan ≥ 14 days prior to Step 1 registration.
• Participants must not be considered eligible for hematopoietic stem cell transplantation (HSCT) or have prior HSCT for MF.
• Participants must not have received prior JAK or ACVR1 inhibitor treatment.
• Participants must not have received investigational therapy within 14 days prior to Step 1 registration.
• Participants must not have had a prior splenectomy.
• Participants must not have had splenic irradiation within 90 days prior to Step 1 registration.
• Participants must not have received prior chemotherapy for their MF (e.g., hypomethylating agent, hypomethylating agent + venetoclax).
• Participants must not have had major surgery within 21 days prior to Step 1 registration.
• Participants must not have received a live vaccine within 14 days prior to Step 1 registration.
• Participants must not have grade 2 or higher peripheral neuropathy.
• Participants must not have clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; or unstable angina pectoris. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
• Participants must not have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Participants must not have history of stroke, reversible ischemic neurologic deficit, or transient ischemic attack within 90 days prior to Step 1 registration.
• Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Participants with curatively treated basal or squamous cell skin cancer, superficial bladder cancer, in situ cervical cancer and/or in situ breast cancer may be enrolled.
• Participants must not have uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) as determined by the local investigator.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

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

Condition Hierarchy (Ancestors)

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

Study Officials

• Alexander Coltoff, MD

  SWOG Network Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SWOG Clinical Trials Partnerships SWOG Clinical Trials Partnerships

CONTACT

210-614-8808; ctp@swog.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 27, 2026
• Study Start (Estimated): August 8, 2026
• Primary Completion (Estimated): August 8, 2029
• Study Completion (Estimated): August 8, 2031
• Last Updated: April 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share