Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis (ODYSSEY)

April 17, 2026 updated by: GlaxoSmithKline

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

The purpose of this Phase 2 study is to evaluate the efficacy and safety of momelotinib (MMB) in combination with luspatercept (LUSPA) in participants with transfusion dependence (TD) primary myelofibrosis (PMF) or Post-polycythemia vera (PV)/ essential thrombocythemia (ET) myelofibrosis (MF) who are either janus kinase (JAK) inhibitor (JAKi) naïve or experienced.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

68

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lynda Foltz
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Principal Investigator:
          • Vikas Gupta
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jonathan How
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Shireen Sirhan
  • France
      • Angers, France, 49933
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Francoise BOYER
        • Contact:
        • Contact:
      • Brest, France, 29609
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jean Christophe IANOTTO
      • Lyon, France, 69004
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Fiorenza BARRACO
        • Contact:
        • Contact:
      • Nice, France, 06202
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael Loschi
      • Nîmes, France, 30029
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Stefan Wickenhauser
      • Paris, France, 75010
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Jean-Jacques Kiladjian
        • Contact:
        • Contact:
      • Poitiers, France, 86021
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jose Torregrosa Diaz
  • Germany
      • Essen, Germany, 45147
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Joachim R. Goethert
      • Jena, Germany, 07747
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Carl Crodel
      • Lübeck, Germany, 23538
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nikolas von Bubnoff
      • Mannheim, Germany, 68167
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Andreas Reiter
  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • FRANCESCA PALANDRI
        • Contact:
        • Contact:
      • Catania, Italy, 95123
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Giuseppe Palumbo
      • Florence, Italy, 50134
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Alessandro Vannucchi
        • Contact:
        • Contact:
      • Meldola FC, Italy, 47014
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Alessandro Lucchesi
        • Contact:
        • Contact:
      • Milan, Italy, 20122
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Barbara Mora
      • Roma, Italy, 161
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Massimo Breccia
  • Spain
      • Badalona, Spain, 08005
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • Blanca Xicoy Cirici
        • Contact:
        • Contact:
      • Barcelona, Spain, 8035
        • Recruiting
        • GSK Investigational Site
        • Principal Investigator:
          • María Laura Fox
        • Contact:
        • Contact:
      • Las Palmas, Spain, 35020
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Maria Teresa Gomez Casares
      • Madrid, Spain, 28034
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Valentin Garcia
      • Madrid, Spain, 28009
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Santiago Osorio Prendes
      • Málaga, Spain, 29010
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Regina Garcia Delgado
      • Valencia, Spain, 46026
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Elvira Mora Castera
  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kristen Pettit
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Brian Chernak
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jonathan Abbas
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Prithviraj Bose
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • GSK Investigational Site
        • Contact:
        • Contact:
        • Principal Investigator:
          • Vivian Oehler

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Momelotinib + Luspatercept
Participants with transfusion dependent primary myelofibrosis or post- PV/ ET myelofibrosis that is JAKi naïve or JAKi experienced will receive momelotinib and luspatercept.
Drug: Momelotinib
Momelotinib will be administered orally.
Other Names:
  • Ojjaara; CYT387
Drug: Luspatercept
Luspatercept will be administered subcutaneously.
Other Names:
  • REBLOZYL; ACE-536

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants with TI Response by Week 24
Time Frame: Up to Week 24
TI response is defined as not requiring red blood cell (RBC) transfusion (except in the case of clinically overt bleeding) for any ≥12-week interval.
Up to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
Time Frame: Up to approximately 36 weeks
Up to approximately 36 weeks
Number of Participants with Clinically Important Changes in Laboratory Parameters, Vital Signs, and Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame: Up to Week 24
Up to Week 24
Percentage of Participants with TI at the End of Week 24
Time Frame: Up to Week 24
TI was defined as not requiring RBC transfusion (except in the case of clinically overt bleeding) for ≥12 weeks preceding Week 24, with all hemoglobin (Hgb) levels during the ≥12-week interval of ≥8 g/dL (except in the case of clinically overt bleeding).
Up to Week 24
Plasma Concentration of MMB
Time Frame: Up to Week 24
Up to Week 24
Plasma Concentration of Morpholino Lactam (M21)
Time Frame: Up to Week 24
Up to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 28, 2025

Primary Completion (Estimated)

March 19, 2027

Study Completion (Estimated)

March 17, 2028

Study Registration Dates

First Submitted

July 19, 2024

First Submitted That Met QC Criteria

July 19, 2024

First Posted (Actual)

July 24, 2024

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 17, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 220752
  • 2024-518225-15 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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