Fedratinib for Myeloproliferative Disorders

Overseen By Maria Urdiales

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: JAK2 inhibitors, Chemotherapy

Disqualifiers: Acute GVHD, Wernicke's encephalopathy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of fedratinib (also known as Inrebic) for treating individuals with myeloproliferative neoplasms (MPNs), a group of diseases affecting blood cell production, after a stem cell transplant. Participants will take varying doses of fedratinib to determine the most effective dose. This trial may suit individuals who have had a successful stem cell transplant for MPNs and are not experiencing disease progression. 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 treatment.

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

Research shows that fedratinib is generally well-tolerated by people with certain blood disorders. This treatment has already received approval in the United States for adults with myelofibrosis, a type of blood cancer. Studies have found that common side effects while taking fedratinib include low red blood cell count (anemia), stomach issues, and changes in liver function. Medical help usually manages these side effects.

However, another drug similar to fedratinib has been linked to heart problems, such as heart attacks or strokes. Monitoring for these issues during treatment is crucial. Overall, current safety data suggests fedratinib is generally safe when used as directed, but ongoing monitoring in trials will provide more information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for myeloproliferative disorders, which often include medications like hydroxyurea and ruxolitinib that typically target specific pathways or reduce blood cell counts, Fedratinib works by inhibiting the Janus kinase 2 (JAK2) enzyme. This mechanism offers a fresh approach by directly targeting the molecular drivers of the disease. Researchers are excited about Fedratinib because it has the potential to specifically address the underlying cause of the disorder, possibly leading to more effective management of symptoms and disease progression. Additionally, its oral administration makes it convenient for patients, potentially improving adherence to treatment.

What evidence suggests that fedratinib might be an effective treatment for myeloproliferative disorders?

Research has shown that fedratinib may help treat conditions like myeloproliferative neoplasms (MPNs). In studies, about 30-45% of patients experienced a noticeable decrease in spleen size, and 35-40% reported overall improvement. One study found that 53% of patients responded well after 24 weeks, with clear improvements in symptoms and spleen size. Additionally, patients taking fedratinib lived longer than those who did not. This trial will evaluate different dosages of fedratinib to determine the most effective dose. These findings suggest that fedratinib could be a promising treatment option for patients with MPNs after a transplant. ^{5 6 7 8 9}

Who Is on the Research Team?

Taiga Nishihori, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults with myeloproliferative neoplasms who've had a stem cell transplant can join this trial. They should be in good physical condition, understand the study, and follow its schedule. Women of childbearing age must test negative for pregnancy and use effective birth control; men must also practice safe sex or abstinence.

Inclusion Criteria

I have skin GVHD but am responding to a low dose of prednisone.

I am able to care for myself and perform daily activities.

I have a Philadelphia chromosome negative blood disorder and had a bone marrow transplant.

Exclusion Criteria

I have been diagnosed with chronic liver disease.

I am currently receiving treatment for acute GVHD affecting my gut or liver.

Thiamine levels below the normal range

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive fedratinib at varying doses to determine the Recommended Phase 2 Dose (RP2D)

Up to 1 year

Treatment Phase 2

Participants receive fedratinib at the RP2D determined in Phase 1

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Fedratinib

Trial Overview The trial is testing fedratinib pills as a maintenance therapy to prevent cancer from returning after a stem cell transplant. Participants will take the medication orally to see if it's effective and safe in maintaining their health post-transplant.

How Is the Trial Designed?

Group I: Phase 2: Treatment at Recommended Phase 2 Dose (RP2D) Experimental Treatment 1 Intervention

Participants will take fedratinib at the dose determined in the phase 1 portion of this study, once daily by mouth.

Group II: Phase 1: Dose Level 3 Experimental Treatment 1 Intervention

Participants will take 400 mg fedratinib once daily by mouth.

Group III: Phase 1: Dose Level 2 Experimental Treatment 1 Intervention

Participants will take 300 mg fedratinib once daily by mouth.

Group IV: Phase 1: Dose Level 1 Experimental Treatment 1 Intervention

Participants will take 200 mg fedratinib once daily by mouth.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11845104/

Real-world treatment patterns and health outcomes for ... Kaplan-Meier estimates of median progression-free and overall survival from initiation were 23.8 months (95% CI, 21.1–27.6) and 29.8 months (95% ...

2. nature.com nature.com/articles/s41408-025-01211-1

Fedratinib for the treatment of myelofibrosis In these trials, fedratinib achieved significant spleen volume reduction in ~30–45% of patients and improvement in total symptom scores in 35–40 ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/8/1907/535590/Fedratinib-in-2025-and-beyond-indications-and

Fedratinib in 2025 and beyond: indications and future ... Survival at 1 year after ruxolitinib was 71.6% in the fedratinib group vs 47.9% in the non-fedratinib group. Frontline, JAKi naive. JAKARTA was a phase 3 trial ...

4. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00212-6/abstract

Efficacy and safety of fedratinib in patients with ... At data cutoff (Dec 27, 2022), median survival follow-up was 64·5 weeks (IQR 37·9–104·9). SVR35 at end of cycle 6 was seen in 48 (36%) of 134 ...

5. targetedonc.com targetedonc.com/view/fedratinib-shows-promise-in-rare-myeloproliferative-neoplasms

Fedratinib Shows Promise in Rare Myeloproliferative ... A total of 53% of patients achieved a response at 24 weeks, including 50% symptom responses and 37.5% spleen responses. Of those treated for ≥24 ...

6. nature.com nature.com/articles/s41375-020-0954-2

Fedratinib, a newly approved treatment for patients with ... Fedratinib is a selective oral JAK2 inhibitor recently approved in the United States for treatment of adult patients with intermediate-2 or high-risk MF.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38838026/

Safety and efficacy of fedratinib in patients with ... The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients.

8. inrebicpro.com inrebicpro.com/efficacy-safety

INREBIC® (fedratinib) Efficacy and Safety | For Healthcare ... Major Adverse Cardiac Events (MACE): Another JAK inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke in ...

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2330618

Safety and Efficacy of Fedratinib in Patients With Primary or ... Common adverse events with fedratinib treatment were anemia, gastrointestinal symptoms, and increased levels of liver transaminases, serum ...