NILG-HES1-03: Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes

Sponsor

Northern Italy Leukemia Group (Other)

Overall Status

Completed

CT.gov ID

NCT00787384

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

6.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypereosinophilic Syndrome Chronic Eosinophilic Leukemia Chronic Idiopathic Hypereosinophilia	Drug: Imatinib	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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. Other Names: Gleevec

Arm

Intervention/Treatment

Experimental: 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.

Drug: Imatinib

Other Names:

Gleevec

Outcome Measures

Primary Outcome Measures

Response rate []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	USC Ematologia Ospedali Riuniti di Bergamo	Bergamo	Italy	24128
2	Divisione di Ematologia Spedali Civili di Brescia	Brescia	Italy
3	USC Ematologia Azienda Ospedaliera Università Careggi	Firenze	Italy	50134
4	UO Ematologia, Azienda Ospedaliera ULSS6	Vicenza	Italy	36100