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Combining Momelotinib and Luspatercept for Myelofibrosis Treatment

A Phase 2 Open-label Study to Evaluate Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Primary or Secondary Myelofibrosis

Phase 2 Interventional GlaxoSmithKline · NCT06517875

This study is testing if combining two medications, momelotinib and luspatercept, can help people with myelofibrosis who need blood transfusions feel better and reduce their transfusion needs.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment68 (estimated)
Ages18 Years and up
SexAll
SponsorGlaxoSmithKline Industry-sponsored
Drugs / interventionsruxolitinib, fedratinib, momelotinib
Locations33 sites (Ann Arbor, Michigan and 32 other locations)
Trial IDNCT06517875 on ClinicalTrials.gov

What this trial studies

This Phase 2 study evaluates the safety and efficacy of momelotinib in combination with luspatercept for patients with transfusion-dependent primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis. Participants must be either naïve to JAK inhibitors or have previously been treated with specific JAK inhibitors. The study aims to assess the impact of this combination therapy on patients' transfusion needs and overall health outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed diagnoses of primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis who are transfusion-dependent.

Not a fit: Patients who do not have transfusion-dependent myelofibrosis or those with other forms of myelofibrosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the need for blood transfusions in patients with myelofibrosis.

How similar studies have performed: Other studies have shown promising results with JAK inhibitors and therapies targeting anemia in myelofibrosis, suggesting potential for success with this combination approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Is age ≥18 years.
2. Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post-PV/ET myelofibrosis in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria.
3. JAKi naïve or previously treated with either ruxolitinib or fedratinib for PMF or Post-PV/ET myelofibrosis for ≥90 days, or ≥28 days if JAKi therapy is complicated by RBC transfusion requirement of ≥4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma.
4. High risk, intermediate-2, or intermediate-1 risk as defined by Dynamic International Prognostic Scoring System (DIPSS) \[Passamonti, 2010\] or DIPSS-plus \[Gangat, 2011\].
5. TD defined as requiring RBC transfusion ≥4 units or HgB \< 8 g/dL in the 8 weeks prior to the first dose of study treatment (NOTE: 2 consecutive Hgb \< 8 g/dL, at least 1 week apart are required; Hgb values impacted by transfusions are excluded). Only transfusions given when Hgb levels are ≤9.5 g/dL are counted towards TD. RBC transfusions given for clinically overt bleeding, or accident/injury (as assessed by the investigator) are not counted towards TD.

Exclusion Criteria:

1. History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (e.g., uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study intervention or result in inability to swallow oral medications.
2. Participants with an invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years.
3. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, gastrointestinal bleeding, or thalassemia.
4. Uncontrolled intercurrent illness:

   1. Active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial);
   2. Significant active or chronic bleeding event ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to the first dose of study treatment; or
   3. Uncontrolled acute and chronic liver disease (e.g., Child-Pugh score ≥10) OR has current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
5. Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, that is not resolved at the time of the first dose of study treatment.
6. Any of the following in conditions within 6 months prior to the first dose of study intervention:

   1. Unstable angina pectoris; OR
   2. Symptomatic congestive heart failure; OR
   3. Uncontrolled cardiac arrhythmia
7. QTc interval \>450 msec or QTc \>480 msec for participants with bundle branch block.
8. Participants with stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to the first dose of study intervention.
9. History of porphyria.
10. Presence of peripheral neuropathy ≥Grade 2 per CTCAE v5.0.
11. Use of the following treatments within the time periods noted NOTE: All active anti-MF therapy must discontinue at least 1 week prior to the start of baseline MFSAF recording (Study Day -7):

    1. Active anti-MF therapy within 28 days or 5 half-lives, whichever is shorter (exception is prior JAKi therapy).
    2. Steroid use for the treatment of myelofibrosis is prohibited within 14 days prior to the first dose of study treatment until discontinuation of study treatment. Supportive care including steroids for non-myelofibrosis indications may be used.
    3. Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of study intervention.
    4. Any prior investigational agent for myelofibrosis within 4 weeks prior to the first dose of study treatment.
    5. Erythropoiesis stimulating agent (ESA) within 4 weeks prior to the first dose of study treatment.
    6. Splenic irradiation within 3 months prior to the first dose of study treatment.
12. Prior treatment with MMB.
13. Prior treatment with TGF-β pathway ligand traps (e.g., luspatercept or sotatercept).
14. Prior splenectomy.
15. Inability or unwillingness to comply with the protocol restrictions on myelofibrosis therapy and other medications prior to and during study treatment.
16. Unresolved non-hematologic toxicities from prior therapies that are \>Grade 1 per CTCAE v5.0 unless otherwise specified.
17. Known positive status for human immunodeficiency virus (HIV).
18. Hepatitis A, B, or C status as defined below:

    1. Chronic active or acute viral hepatitis A.
    2. Active Hepatitis B infection indicated by the presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to the first dose of study intervention.
    3. Positive hepatitis C antibody test result at screening or within 3 months before the first dose of study intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained.
19. Women who are already pregnant or lactating.

Where this trial is running

Ann Arbor, Michigan and 32 other locations

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 Primary MyelofibrosisMyelofibrosisPost-polycythemia Vera MyelofibrosisPost-essential Thrombocythemia MyelofibrosisMomelotinibLuspaterceptSecondary MyelofibrosisJAK inhibitor
Last reviewed 2026-06-10 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.