Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes

Hypereosinophilic Syndrome Clinical Trial

— NILG-HES1-03  

Official title:

Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00787384
• Other study ID #: NILG-HES1-03
• Secondary ID: EUDRACT 2004-002
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2008
• Last updated: December 28, 2010
• Start date: October 2004
• Est. completion date: December 2007

Study information

• Verified date: December 2010
• Source: Northern Italy Leukemia Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Eosinophilic Leukemia
• Chronic Idiopathic Hypereosinophilia
• Eosinophilia
• Hypereosinophilic Syndrome
• Syndrome

Intervention

Drug:
• 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 wsa discontinued after 12 total weeks of therapy.

Locations

Country	Name	City	State
Italy	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

Sponsors (1)

Lead Sponsor	Collaborator
Northern Italy Leukemia Group

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Intermesoli T, Delaini F, Acerboni S, Salmoiraghi S, Spinelli O, Guerini V, Vannucchi AM, Mappa S, Rossi G, Rossi V, Di Bona E, Paratore S, Carobbio A, Rambaldi A, Barbui T, Bassan R. A short low-dose imatinib trial allows rapid identification of responsi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate			No
Secondary	Safety: Adverse events and serious adverse events			Yes
Secondary	Time to response			No
Secondary	Diagnostic profile of Imatinib-responsive cases			No
Secondary	Duration of responses following drug withdrawal after 12 weeks			No