Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes

Phase 2

Completed

• Conditions: Hypereosinophilic Syndrome; Chronic Eosinophilic Leukemia; Chronic Idiopathic Hypereosinophilia
• Interventions: Drug: Imatinib

• Registration Number: NCT00787384
• Lead Sponsor: Northern Italy Leukemia Group

Brief Summary

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 disease subtype; 3) long-term outcome of HES, CEL and CIH patients treated with Imatinib; 4) safety and tolerability of Imatinib administration.

Detailed Description

Hypereosinophilic syndrome (HES), chronic eosinophilic leukaemia (CEL) and chronic idiopathic hypereosinophilia (CIH) are rare disorders characterized by chronic hypereosinophilia with possible damage to various organs due to eosinophilic infiltration and release of cytokines. The therapies of these diseases are largely unsatisfactory and based on the use of a variety of antiproliferative drugs such as corticosteroids, interferon-alfa, cyclosporine, vincristine or hydroxyurea. More often the responses are transient and patients need numerous treatment lines.

In 2001 Schaller et al reported the first case of a patient with HES resistant to conventional treatment that responded to imatinib mesylate. (Schaller, MGM 2001). After that, many authors described cases with hypereosinophilia that achieve a rapid response to Imatinib and in 2003 Cools et al identified a novel tyrosine kinase generated from the fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFRalfa gene associated to hypereosinophilia.

The optimal dose of Imatinib in this setting of patients is still unknown; however, the demonstration of effective and safe clinical doses in a variety of currently studied malignant diseases, suggests that a dose of 100 mg/day increasing weekly of 100 mg/day (maximum dose 400 mg/day), may be employed.

We designed a phase II trial to investigate the clinical anti-proliferative activity, safety and tolerability of escalating doses of Imatinib (entry dose 100 mg/d)administered for 12 total weeks in HES, CEL and CIH patients.

Study Timeline

• Study Start: 2004-10
• Primary Completion: 2007-12
• Study Completion: 2007-12
• Study First Submitted: 2008-11-06
• Study First Submitted QC: 2008-11-06
• Study First Posted: 2008-11-07
• Status Verified: 2010-12
• Last Update Submitted: 2010-12-28
• Last Update Posted: 2010-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• patients with a diagnosis of HES, CEL and CIH, who are either previously untreated or have been treated with corticosteroids, cytotoxic drugs, and IFN.
• age > 15 years.
• signature of a written informed consent(by parents/tutors for patients aged < 18 years).

Exclusion Criteria

• patients with a diagnosis of secondary hypereosinophilia
• age < 15 years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Imatinib	Imatinib	Patients received oral imatinib 100 mg/d; in case of unsatisfactory response (less than complete) Imatinib could be increased by 100 mg/die on a weekly basis and up to a maximum of 400 mg/die. Imatinib was discontinued after 12 total weeks of therapy.

Primary Outcome Measures

Name	Time	Method
Response rate

Secondary Outcome Measures

Name	Time	Method
Safety: Adverse events and serious adverse events
Time to response
Diagnostic profile of Imatinib-responsive cases
Duration of responses following drug withdrawal after 12 weeks

Trial Locations

Locations (4)

USC Ematologia Ospedali Riuniti di Bergamo; 🇮🇹 Bergamo, Italy

Divisione di Ematologia Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

USC Ematologia Azienda Ospedaliera Università Careggi; 🇮🇹 Firenze, Italy

UO Ematologia, Azienda Ospedaliera ULSS6; 🇮🇹 Vicenza, Italy