Momelotinib for Myelofibrosis

Overseen By Gabriela Hobbs, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Momelotinib

Must not be taking: JAK inhibitors, Immunosuppressants

Disqualifiers: Surgery, Infection, Liver disease, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called momelotinib to determine its safety and tolerability for people with myelofibrosis, a type of bone marrow cancer, during and after a bone marrow transplant. Participants will receive momelotinib alongside their usual transplant procedure to assess its effectiveness and how the body processes it. The trial seeks individuals with confirmed myelofibrosis who need a bone marrow transplant and may have specific risk factors, such as requiring frequent blood transfusions or possessing certain genetic markers. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

If you are currently taking JAK inhibitors other than momelotinib, you will need to switch to momelotinib before starting the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that momelotinib is likely to be safe for humans?

Research has shown that momelotinib is generally well-tolerated by patients with myelofibrosis. Studies have found that patients taking momelotinib often experience a good response and improvements in quality of life, particularly for anemia-related symptoms. Long-term safety data indicate that many patients continued treatment for several years, suggesting that serious side effects might not be common.

In one study, only a small percentage of patients experienced severe issues over a long treatment period, suggesting the drug might be safe for long-term use. However, since this trial is in its early stages, discussing any concerns with the study team is advisable. They can provide detailed information about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Momelotinib is unique because it offers a fresh approach to treating myelofibrosis, a type of bone marrow cancer, by targeting specific pathways involved in disease progression. Unlike other treatments that primarily focus on symptom management and blood transfusions, Momelotinib works by inhibiting the JAK1, JAK2, and ACVR1 pathways, potentially reducing the need for transfusions and improving overall blood counts. Researchers are excited about Momelotinib because it could streamline the treatment process by being administered orally, enhancing patient convenience and adherence, especially when combined with standard hematopoietic cell transplantation.

What evidence suggests that momelotinib might be an effective treatment for myelofibrosis?

Research has shown that momelotinib may help treat myelofibrosis, a type of bone marrow disorder. In studies, patients taking momelotinib reported a better quality of life, particularly those with anemia, a condition characterized by a lack of healthy red blood cells. One study found that 71.5% of patients who took momelotinib as part of a combination treatment responded positively after three months. Another study showed that momelotinib helped 30% of patients stop needing blood transfusions after 24 weeks. In this trial, participants will receive momelotinib alongside standard of care hematopoietic cell transplantation (HCT). These findings suggest that momelotinib could be a useful option for managing symptoms of myelofibrosis. ^{3 6 7 8 9}

Who Is on the Research Team?

Gabriela Hobbs, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with myelofibrosis who haven't been treated with JAK inhibitors, are eligible for a specific type of bone marrow transplant (HCT), and meet certain disease severity criteria. They must not be pregnant, agree to use contraception, and have no recent major surgeries or other serious health conditions.

Inclusion Criteria

I am not currently taking JAK inhibitors for myelofibrosis.

I am over 18 years old.

Participants must have specific donor types for HCT eligibility

Exclusion Criteria

I have not had major surgery or taken new, unapproved drugs or immunosuppressants recently.

I had cancer before, but it meets the trial's specific criteria.

Pregnant, lactating, planning pregnancy, or unwilling to use contraception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Pre-Transplant

Participants receive reduced intensity conditioning regimen before HCT, including Fludarabine and Mephalan, and start momelotinib 7 days before HCT

1 week

1 visit (in-person)

Hematopoietic Cell Transplantation (HCT)

Participants undergo standard of care allogeneic HCT and continue momelotinib treatment

1 day

1 visit (in-person)

Post-Transplant Treatment

Participants continue momelotinib treatment for up to 1 year post-HCT, with dose adjustments as needed

364 days

Follow-up

Participants are monitored for safety, effectiveness, and incidence of GVHD and other outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Momelotinib

Trial Overview The study tests the safety of momelotinib in patients with myelofibrosis during and after undergoing hematopoietic cell transplantation (HCT). It's an early-phase trial at one center where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Momelotinib + Standard of Care (SOC) Hematopoietic Cell Transplantation (HCT) Experimental Treatment 1 Intervention

Momelotinib will be administered orally once daily at a pre-determined dose starting 7 days before standard of care (SOC) hematopoietic cell transplantation (HCT) and for up to 1 year after HCT, for a total of 13 28-day cycles. Participants will receive SOC HCT and HCT treatment including: reduced intensity conditioning (RIC) regimen before HCT (Fludarabine, Mephalan), and tacrolimus and methotrexate after HCT, all administered according to SOC.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

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GlaxoSmithKline

Chief Executive Officer since 2017

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GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006532/

Real world outcomes of momelotinib in myelofibrosis patients ... At the 3-month follow-up, the overall response rate (major + minor) was 71.5% in the combination treatment group and 50% in the monotherapy ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6652/528227/Efficacy-and-Safety-of-Momelotinib-in

Efficacy and Safety of Momelotinib in Myelofibrosis: A ... Conclusions: MF patients treated with momelotinib demonstrated good response and improved quality of life, particularly in anemia-related ...

3. mpn-hub.com mpn-hub.com/medical-information/momelotinib-for-the-treatment-of-mf-long-term-data

Momelotinib for the treatment of MF: Long-term data At Week 24, transfusion independence response rates were 30% with momelotinib and 20% with danazol.6 At Week 48, 57% of patients who continued ...

4. nature.com nature.com/articles/s41408-025-01275-z.pdf

Real world outcomes of momelotinib in myelofibrosis ... MoReLife – real-life data support the potential of momelotinib as a safe and effective treat- ment option for cytopenic myelofibrosis patients.

5. jh.elmerpub.com jh.elmerpub.com/JH/article/view/2094

Efficacy and Safety of Momelotinib in Myelofibrosis Primary outcomes included spleen volume reduction (≥ 35%) and anemia response (transfusion independence). Secondary endpoints included symptom ...

6. nature.com nature.com/articles/s41408-025-01275-z

Real world outcomes of momelotinib in myelofibrosis ... Our results support that momelotinib is an effective and well-tolerated treatment for MF patients in routine clinical practice, demonstrating ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10368854/

Momelotinib long-term safety and survival in myelofibrosis As of the data cutoff (3 December 2021), 12.1% of patients were treated for ≥5 years, including 75% of patients (88/118) who continued momelotinib in the XAP; ...

8. mpn-hub.com mpn-hub.com/medical-information/long-term-survival-and-safety-outcomes-with-momelotinib

Long-term survival and safety outcomes with momelotinib Long-term survival data · Death: 45.2% vs 44.2%. · Leukemic transformation: 6.7% vs 1.9%. · Median OS: 2.9 years vs 3.1 years (hazard ratio, [HR], ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124094783

Efficacy and Safety of Momelotinib in Myelofibrosis: A ... Conclusions: MF patients treated with momelotinib demonstrated good response and improved quality of life, particularly in anemia-related ...