Clinical trial NCT00787384: Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes
Official title: Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypereosinophilic Syndrome
Chronic Eosinophilic Leukemia
Chronic Idiopathic Hypereosinophilia
Keywords: Hypereosinophilic syndrome (HES)
chronic eosinophilic leukaemia (CEL)
chronic idiopathic hypereosinophilia (CIH)
Imatinib
Response
Timing to response
Lead sponsor: Northern Italy Leukemia Group
Sponsor class: OTHER
First posted: 2008-11-07
Enrollment: 25
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate
Secondary outcomes:
measure: Safety: Adverse events and serious adverse events
measure: Time to response
measure: Diagnostic profile of Imatinib-responsive cases
measure: Duration of responses following drug withdrawal after 12 weeks
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: USC Ematologia Ospedali Riuniti di Bergamo
city: Brescia
country: Italy
facility: Divisione di Ematologia Spedali Civili di Brescia
city: Firenze
country: Italy
facility: USC Ematologia Azienda Ospedaliera Università Careggi
city: Vicenza
country: Italy
facility: UO Ematologia, Azienda Ospedaliera ULSS6
Study officials:
affiliation: USC Ematologia Ospedali Riuniti di Bergamo
name: Renato Bassan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 responsive patients in hypereosinophilic syndromes. Br J Haematol. 2009 Dec;147(5):681-5. doi: 10.1111/j.1365-2141.2009.07893.x. Epub 2009 Sep 4.