Fedratinib for Leukemia

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Chemotherapy, Immunomodulatory, Ruxolitinib, others

Disqualifiers: Pregnancy, Encephalopathy, Liver disease, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called fedratinib (also known as Inrebic) to evaluate its effectiveness and safety for individuals with certain blood cancers, such as myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic neutrophilic leukemia (CNL). Participants will take fedratinib daily to determine its impact on managing their condition. Suitable candidates have a confirmed diagnosis of one of these specific blood disorders and experience issues like an enlarged spleen affecting daily life. The study aims to determine if fedratinib can serve as a beneficial treatment option. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as chemotherapy, immunomodulatory drugs, and some other specific treatments. However, you can continue taking hydroxyurea if it's being used to control leukocytosis and has been stable for more than 14 days before starting the study drug.

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

Research has shown that fedratinib has undergone safety testing in several studies. In one study, about 1% of patients experienced possible cases of Wernicke's encephalopathy, a rare brain disorder, highlighting the need to monitor vitamin B1 (thiamine) levels in patients taking the drug. Additionally, studies indicate that patients generally tolerate fedratinib's side effects. Many patients, including those unable to use other JAK inhibitors for blood disorders, have used it safely. Overall, fedratinib is considered safe enough for further study in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia, which often include chemotherapy and stem cell transplants, Fedratinib acts on a unique pathway by targeting the JAK2 enzyme, which plays a crucial role in the growth of cancer cells. This specific mechanism of action could offer a new option for patients who might not respond well to existing therapies. Researchers are excited about Fedratinib because it represents a potential shift towards more targeted and possibly less toxic treatment strategies for leukemia, offering hope for improved outcomes with fewer side effects.

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

Research has shown that fedratinib, which participants in this trial will take, may help treat certain blood disorders, specifically myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic neutrophilic leukemia (CNL). One study found that 85% of patients with symptoms who took the treatment for at least 24 weeks felt much better. Another study reported a 32% average reduction in spleen size in patients treated for the same period. These findings suggest that fedratinib might effectively reduce symptoms and improve the quality of life for people with these conditions. ^{4 6 7 8 9}

Who Is on the Research Team?

Andrew Kuykendall, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults with certain blood disorders like MDS/MPNs or CNL, who can swallow pills and have not been treated with fedratinib before. They must understand the study and agree to use effective contraception. Excluded are those with thiamine deficiency, serious infections, on specific drugs that affect fedratinib, pregnant women, or those with other major health issues.

Inclusion Criteria

Patient must be able to adhere to the study visit schedule and other protocol requirements

Patient must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted

I am able to become pregnant and agree to use strong birth control or abstain from sex during the study.

Exclusion Criteria

I had major surgery or radiation therapy within the last four weeks.

I agree to use effective contraception while on the study treatment.

Patient with known human immunodeficiency virus (HIV), active infectious Hepatitis B (Hep B), and/or active Hepatitis C (Hep C)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fedratinib by mouth once a day every day of each 28-day cycle

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fedratinib

Trial Overview The trial is testing the effectiveness of a pill called fedratinib for treating blood disorders such as MDS/MPNs and CNL. It aims to see how safe it is for patients and if there are any side effects when taking this medication.

How Is the Trial Designed?

Group I: Treatment with Fedratinib Experimental Treatment 1 Intervention

Participants will taken Fedratinib by mouth once a day every day of each 28 day cycle.

Fedratinib is already approved in United States, European Union for the following indications:

Approved in United States as Inrebic for:

• Myelofibrosis

Approved in European Union as Inrebic for:

• Myelofibrosis

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

Published Research Related to This Trial

In the phase II JAKARTA2 study involving 97 patients with intermediate- or high-risk myelofibrosis who were resistant or intolerant to ruxolitinib, fedratinib demonstrated a spleen volume response rate of 31%, indicating its efficacy in reducing spleen size.

Despite the positive outcomes, the treatment was associated with significant side effects, including grade 3-4 anemia in 38% of patients and thrombocytopenia in 22%, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure. Harrison, CN., Schaap, N., Vannucchi, AM., et al.[2022]

Citations

1. 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 ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/481/530695/A-Phase-2-Study-of-Fedratinib-in-Patients-with-MDS

A Phase 2 Study of Fedratinib in Patients with MDS/MPN and ... Among 13 pts with symptomatic disease at baseline who were treated for ≥ 24 weeks, 11 (85%) experienced an improvement in TSS by an average of - ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39265613/

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 ...

4. targetedonc.com targetedonc.com/view/fedratinib-shows-promise-in-chronic-neutrophilic-leukemia-and-mds-mpn

Fedratinib Shows Promise in Chronic Neutrophilic ... Among those treated for ≥24 weeks, spleen volume decreased by an average of 32%, and 85% showed symptomatic improvement. Responses were enriched ...

5. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(23)02130-4/fulltext

Real-World Use of Fedratinib for Myelofibrosis Following ... Patient-reported outcomes were also evaluated: Myelofibrosis Symptom Assessment Form (MFSAF) data revealed an improvement in Total Symptom Score ...

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

Fedratinib, a newly approved treatment for patients with ... Suspected cases of Wernicke's encephalopathy were reported during fedratinib trials in ~1% of patients; thiamine levels should be monitored ...

7. inrebicpro.com inrebicpro.com/efficacy-safety

INREBIC® (fedratinib) Efficacy and Safety | For Healthcare ... INREBIC as initial JAK therapy was studied in a pivotal Phase 3 trial. Efficacy and safety were established in the JAKARTA trial.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12008686/

Fedratinib in 2025 and beyond: indications and future ... Fedratinib has data supporting its use in the second-line setting after intolerance or resistance to first-line JAKi, as well as randomized phase 3 data in ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/inrebic-epar-product-information_en.pdf

Inrebic, INN-fedratinib - EMA Summary of the safety profile. The overall safety information of Inrebic was assessed in 608 patients who received continuous doses of Inrebic in Phase 1, 2 ...