Clinical Trial: Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes
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 Summary:
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.
Sponsor: Northern Italy Leukemia Group
Current Primary Outcome: Response rate
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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
Original Secondary Outcome: Same as current
Information By: Northern Italy Leukemia Group
Dates:
Date Received: November 6, 2008
Date Started: October 2004
Date Completion:
Last Updated: December 28, 2010
Last Verified: December 2010
