Momelotinib + Luspatercept for Myelofibrosis

(ODYSSEY Trial)

Recruiting at 13 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Steroids, CYP3A4 inducers, ESAs

Disqualifiers: Invasive malignancy, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with myelofibrosis, a bone marrow disorder that can lead to a need for blood transfusions. Researchers are testing two drugs, momelotinib and luspatercept (which helps improve red blood cell production), to determine if they can reduce the need for transfusions and enhance participant safety. The trial seeks participants with transfusion-dependent myelofibrosis who have either not tried or have already used certain existing treatments. Participants should regularly require blood transfusions due to their condition. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop any active anti-myelofibrosis therapy at least 1 week before starting the study. Steroids for myelofibrosis must be stopped 14 days before the study, and certain other medications like potent CYP3A4 inducers should be stopped 14 days prior. Please consult with the study team for guidance on other medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using momelotinib and luspatercept together may help treat patients with transfusion-dependent myelofibrosis. In earlier studies, some patients taking momelotinib experienced side effects such as low platelet counts, diarrhea, infections, and liver problems. However, not all patients had these side effects, and their severity varied.

Early results also suggest that momelotinib might help some patients live longer. Luspatercept is already approved for treating other blood disorders, indicating its safety for people. While both treatments have been studied individually, their combination is still being tested for safety and effectiveness. Joining this study offers a chance to see if this new combination can benefit people with similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Momelotinib and Luspatercept for myelofibrosis because it offers a novel approach to treating this condition. Unlike standard treatments, such as JAK inhibitors that primarily target inflammation, Momelotinib not only inhibits JAK pathways but also reduces hepcidin levels, potentially alleviating anemia. Luspatercept further complements this by enhancing red blood cell production, offering a unique dual-action strategy that directly addresses both anemia and disease symptoms. This innovative combination could provide more comprehensive relief for patients, tackling aspects of myelofibrosis that current therapies might not fully address.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

Studies have shown that momelotinib can reduce symptoms such as an enlarged spleen and low blood cell counts in people with myelofibrosis. Luspatercept has improved anemia (low red blood cell count) and reduced the need for blood transfusions in patients with myelofibrosis. In this trial, participants will receive a combination of momelotinib and luspatercept to address both the symptoms of myelofibrosis and the need for blood transfusions. Research indicates that using momelotinib and luspatercept together could provide a more comprehensive approach to managing myelofibrosis by targeting different aspects of the disease. Early findings suggest this combination could be promising for patients who either haven't tried JAK inhibitors or didn't benefit sufficiently from them. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high to intermediate risk primary myelofibrosis or post-PV/ET myelofibrosis, as per specific criteria. Participants can be new to JAK inhibitor treatment or have had previous treatments but must require regular blood transfusions due to low hemoglobin levels.

Inclusion Criteria

I have been diagnosed with PMF or myelofibrosis following PV/ET, according to WHO or IWG-MRT standards.

I have taken JAK inhibitors for myelofibrosis, or stopped due to side effects or needing blood transfusions.

My condition is classified as high or intermediate risk by DIPSS standards.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive momelotinib and luspatercept for the treatment of transfusion dependent myelofibrosis

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Luspatercept
• Momelotinib

Trial Overview The study tests the combination of two drugs, Momelotinib and Luspatercept, in patients who depend on transfusions due to myelofibrosis. It aims to see if this drug duo is effective and safe for those who are either new or experienced with JAK inhibitor therapies.

How Is the Trial Designed?

Group I: Momelotinib + Luspatercept Experimental Treatment 2 Interventions

Participants with transfusion dependent primary myelofibrosis or post- PV/ ET myelofibrosis that is JAKi naïve or JAKi experienced will receive momelotinib and luspatercept.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06517875

NCT06517875 | Study of Momelotinib in Combination With ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06517875?term=MOMELOTINIB&rank=5

Study of Momelotinib in Combination With Luspatercept ... 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 ...

3. ashpublications.org ashpublications.org/bloodadvances/article/8/17/4511/516341/Safety-and-efficacy-of-luspatercept-for-the

Safety and efficacy of luspatercept for the treatment of anemia ... In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8824279/

Updates on Clinical Trials for Myelofibrosis Momelotinib and pacritinib are JAKi in phase III trials with encouraging results for improving splenomegaly or cytopenias (Harrison et al., 2019; Tefferi et al.

5. withpower.com withpower.com/trial/phase-2-polycythemia-vera-11-2024-0bc53

Momelotinib + Luspatercept for 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 ...

6. mpn-hub.com mpn-hub.com/medical-information/novel-treatments-momelotinib-and-luspatercept

Novel treatments: Momelotinib and luspatercept A pooled survival analysis from the SIMPLIFY trials suggested that momelotinib was associated with a survival benefit in patients who became TI.

7. ctsearchsupport.org ctsearchsupport.org/clinical-trials/study-of-momelotinib-in-combination-with-luspatercept-in-participants-with-transfusion-dependent-myelofibrosis

Trial Summary | NMDP℠ CTSS To find out if the combination of luspatercept and momelotinib is safe and works well to treat transfusion-dependent myelofibrosis.

8. bloodcancerstoday.com bloodcancerstoday.com/post/odyssey-will-adding-luspatercept-to-momelotinib-reduce-transfusion-dependence-in-patients-with-mf-and-anemia

The Phase 2 Odyssey is Underway for Patients With ... The Odyssey study will evaluate the combination of momelotinib and luspatercept in patients with transfusion-dependent myelofibrosis (MF), ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12058967/

Momelotinib in JAK2 inhibitor-naïve myelofibrosis Common treatment-emergent adverse events included thrombocytopenia (10%, ≥grade 3 6%), diarrhea (12%), infections (9%), hepatotoxicity (6%), and ...