Tyrosine Kinase Inhibitors for Hypereosinophilic Syndrome

Recruiting at 1 trial location

Overseen By Amy D Klion, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Imatinib, Ruxolitinib

Must not be taking: Fluconazole

Disqualifiers: Pregnancy, Systemic mastocytosis, HIV, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests imatinib (Gleevec), a tyrosine kinase inhibitor, to determine if it can safely and effectively reduce high eosinophil levels in people with hypereosinophilic syndrome (HES). Eosinophils, a type of white blood cell, can damage organs when present in excess. The trial seeks individuals with a specific form of HES linked to myeloid disorders or those unresponsive to standard treatments. Participants may qualify if diagnosed with HES and show signs of organ damage related to high eosinophil levels. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that other myelosuppressive agents (drugs that suppress bone marrow activity) will be tapered and discontinued during the first week of therapy with imatinib mesylate. It's best to discuss your current medications with the trial team.

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

Research has shown that imatinib is usually well tolerated by patients. In one study, only 3% to 5% of patients stopped taking it due to side effects. Another study found that serious side effects were rare, with few severe reactions, suggesting that imatinib is relatively safe for most people.

For ruxolitinib, studies have indicated it is also well tolerated. Common side effects include low red blood cell count (anemia) and low platelet count (thrombocytopenia), but these are generally manageable. In one case series, over 80% of patients went into remission, suggesting the treatment is both effective and safe.

Both treatments have demonstrated promising safety in earlier research. While individual experiences may vary, these studies suggest the treatments are generally safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Imatinib and Ruxolitinib for treating Hypereosinophilic Syndrome because they offer unique approaches compared to existing options. Unlike standard treatments that primarily aim to control symptoms, Imatinib works by specifically targeting tyrosine kinases, enzymes that play a crucial role in the overproduction of certain white blood cells. This targeted action could potentially lead to more effective management of the condition. Ruxolitinib, on the other hand, targets a different pathway by inhibiting Janus kinases, which are involved in the immune response. This distinct mechanism may help reduce inflammation and improve symptoms in a novel way. Both treatments represent a shift towards more precise, mechanism-based therapies for Hypereosinophilic Syndrome.

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

Research has shown that the drug imatinib mesylate (Gleevec), which participants in this trial may receive, can help treat hypereosinophilic syndrome (HES). Studies indicate that about 47% of patients responded to the treatment, with nearly 19% experiencing a complete improvement in their blood condition in about 1.5 months. Some patients remained in remission for more than three months. Another treatment option in this trial is ruxolitinib. A study found that it significantly reduced eosinophil counts, which are often elevated in people with HES. This reduction suggests that ruxolitinib could effectively manage HES symptoms. Both treatments show promise, but results can vary depending on the individual. ^{2 3 6 7 8}

Who Is on the Research Team?

Amy D Klion, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for individuals with myeloid hypereosinophilic syndrome, characterized by high eosinophil counts and organ damage. Participants must be at least 2 years old for imatinib or 18+ for ruxolitinib therapy, agree to use effective contraception, and have no secondary causes of their condition. Those already on imatinib may join the dose reduction part of the study.

Inclusion Criteria

Negative serum beta-hCG 24 hours prior to drug administration for women of childbearing potential to exclude early pregnancy

I am willing and able to follow all study rules and attend all appointments.

I have been diagnosed with hypereosinophilic syndrome, showing high eosinophil levels and organ damage.

Exclusion Criteria

Pregnant or nursing women

I am HIV positive or have another known immunodeficiency.

My condition is D816V KIT-positive systemic mastocytosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive imatinib mesylate daily, with weekly monitoring for the first month, then biweekly for 3 months, and monthly thereafter

12 months

Weekly visits for the first month, biweekly for 3 months, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment, with clinical assessments every 3 months

5 years

Every 3 months

Open-label extension

Participants may continue treatment with imatinib mesylate if stable dosing is achieved

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Imatinib

Trial Overview

The trial tests tyrosine kinase inhibitors: imatinib mesylate (Gleevec) starting at 400 mg daily, potentially reduced to 100 mg; and ruxolitinib in eligible patients. It aims to reduce blood eosinophilia in myeloid HES patients, assessing safety and efficacy through regular clinical evaluations.

How Is the Trial Designed?

Group I: Ruxolitinib Experimental Treatment 1 Intervention

open label ruxolitinib treatment

Group II: Imatinib Experimental Treatment 1 Intervention

open label imatinib mesylate treatment

Imatinib is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Gleevec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in United States as Gleevec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in Canada as Glivec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in Japan as Glivec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Approved in Switzerland as Gleevec for:

• Chronic myeloid leukemia
• Gastrointestinal stromal tumors
• Dermatofibrosarcoma protuberans
• Systemic mastocytosis
• Hypereosinophilic syndrome

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Imatinib-mesylate was effective in treating hypereosinophilic syndrome (HES) in three out of four patients, demonstrating its potential as a treatment option.

However, the response to imatinib varied significantly among patients, with only one achieving prolonged remission, suggesting that individual disease mechanisms may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity of response to imatinib-mesylate (glivec) in patients with hypereosinophilic syndrome: implications for dosing and pathogenesis. Musto, P., Falcone, A., Sanpaolo, G., et al.[2019]

Imatinib mesylate was found to induce a durable and complete clinical and biological remission in a 32-year-old man with idiopathic hypereosinophilic syndrome within just 3 weeks, after previous treatments failed.

This treatment appears to be very safe and effective, although the exact mechanism of how it works in this specific syndrome remains unclear, suggesting that other oncogenes may be involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complete remission with imatinib mesylate (Glivec) of an idiopathic hypereosinophilic syndrome associated with a cutaneous mastocytosis after failure of interferon-alpha]. Pottier, P., Planchon, B., Grossi, O.[2019]

Hypereosinophilic syndromes (HES) are linked to immunological issues and can involve various cell types, including T lymphocytes that produce cytokines like IL-5, which play a role in the disease's pathology.

Imatinib mesylate, originally used for chronic myelogenous leukemia, has been effective in treating certain subgroups of HES, particularly those with increased bone marrow mast cells, indicating a potential targeted therapy approach for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hypereosinophilic syndromes: still more heterogeneity. Gleich, GJ., Leiferman, KM.[2022]

Imatinib mesylate has shown efficacy in treating hypereosinophilic syndromes (HES), benefiting about 65% of patients, particularly those with the FIP1L1-PDGFRA fusion gene, which is linked to the overproduction of eosinophils.

The study reviewed clinical features and treatment outcomes in 94 patients, highlighting the importance of identifying specific genetic markers like PDGFRA rearrangements to tailor effective therapies for HES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib mesylate as a novel treatment option for hypereosinophilic syndrome: two case reports and a comprehensive review of the literature. Müller, AM., Martens, UM., Hofmann, SC., et al.[2016]

A 25-year-old man with a rare FIP1L1-PDGFRA-negative hypereosinophilic syndrome experienced severe symptoms, including pericardial effusion and pleuritis, which improved significantly after starting treatment with imatinib mesylate.

Imatinib mesylate, typically used for myeloid variants, showed efficacy in this case, allowing the patient to discontinue corticosteroids after 7 months and remain asymptomatic for 23 months, suggesting its potential as a treatment option for similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficiency of imatinib in polyserositis revealing a FIP1L1-PDGFRA-negative hypereosinophilic syndrome]. Green, L., Kahn, JE., Dufour, JF., et al.[2016]

Idiopathic hypereosinophilic syndrome (HES) can be effectively treated with the tyrosine kinase inhibitor imatinib, especially in patients with the FIP1L1-PDGFRA fusion gene, which predicts a positive response to the treatment.

Imatinib is generally safe with minimal side effects, although there have been rare reports of acute left ventricular dysfunction in some patients during the first week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia]. Chrobák, L., Voglová, J.[2006]

The discovery of the FIP1L1-PDGFRA fusion gene in idiopathic hypereosinophilic syndrome highlights its classification as a chronic eosinophilic leukemia, which affects treatment approaches and understanding of the disease's molecular basis.

Imatinib mesylate (Gleevec) has been shown to effectively target the FIP1L1-PDGFRA fusion kinase, providing a rational treatment option, although resistance may develop, necessitating alternative therapies like PKC412.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Cools, J., Stover, EH., Wlodarska, I., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00787384

Efficacy of Imatinib Mesylate in Hypereosinophilic ...

The study was performed to assess: 1) clinical activity of Imatinib in patients with HES, CEL and CIH; 2) correlation between Imatinib activity and specific ...

2.

haematologica.org

haematologica.org/article/view/4556

The efficacy of imatinib mesylate in patients with FIP1L1 ...

Four of 36 patients achieved a CHR in 1 month, and another patient in 3 months, for an overall CHR rate of 14% (5/36). All five patients who achieved CHR lost ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11637715/

Imatinib is effective in some PDGFRA/B‐negative ...

Respective overall and complete haematological response rates were 46.9% and 18.8%, and the median time to response was 1.5 months. The ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497120506307

Efficacy of imatinib mesylate in the treatment of idiopathic ...

Five patients responded: 4 achieved sustained complete remission lasting a median of 12+ weeks (range, 9+ to 36+ weeks), and 1 had a transient response. One ...

5.

ashpublications.org

ashpublications.org/blood/article/101/9/3391/105823/Imatinib-therapy-for-hypereosinophilic-syndrome

Imatinib therapy for hypereosinophilic syndrome and other ...

We have previously reported the efficacy of imatinib mesylate for the treatment of 5 patients with HES.9 Here, we describe treatment ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/18950453/

Safety and efficacy of imatinib in chronic eosinophilic ...

Overall, imatinib was well tolerated with a low incidence of grade III/IV toxicities. These data confirmed the long-term efficacy of imatinib for PDGFR- ...

7.

mpnresearchfoundation.org

mpnresearchfoundation.org/news/gleevecr-approved-in-the-us-for-five-rare-life-threatening-disorders-with-limited-treatment-options/

GLEEVEC(R) APPROVED IN THE US FOR FIVE RARE ...

Therapy with Gleevec was discontinued for adverse events in 3% to 5% of adult patients with Ph+ CML or Kit+ GIST. None of the 5 patients in the ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2025/219097Orig1s000MedR.pdf

219097Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov

Considering safety and if bioequivalence is established, the clinical review team recommends regular approval of imatinib oral solution, 80 mg/ ...