Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes (NILG-HES1-03)
Chronic Eosinophilic Leukemia
Chronic Idiopathic Hypereosinophilia
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes|
- Response rate [ Designated as safety issue: No ]
- Safety: Adverse events and serious adverse events [ Designated as safety issue: Yes ]
- Time to response [ Designated as safety issue: No ]
- Diagnostic profile of Imatinib-responsive cases [ Designated as safety issue: No ]
- Duration of responses following drug withdrawal after 12 weeks [ Designated as safety issue: No ]
|Study Start Date:||October 2004|
|Study Completion Date:||December 2007|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
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.
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.
Other Name: Gleevec
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00787384
|USC Ematologia Ospedali Riuniti di Bergamo|
|Bergamo, Italy, 24128|
|Divisione di Ematologia Spedali Civili di Brescia|
|USC Ematologia Azienda Ospedaliera Università Careggi|
|Firenze, Italy, 50134|
|UO Ematologia, Azienda Ospedaliera ULSS6|
|Vicenza, Italy, 36100|
|Principal Investigator:||Renato Bassan, MD||USC Ematologia Ospedali Riuniti di Bergamo|