Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes

NCT ID: NCT00787384

Last Updated: 2010-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2007-12-31

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Gleevec

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

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northern Italy Leukemia Group

OTHER

Sponsor Role: lead

Responsible Party

NILG

Principal Investigators

Renato Bassan, MD

Role: PRINCIPAL_INVESTIGATOR

USC Ematologia Ospedali Riuniti di Bergamo

Locations

USC Ematologia Ospedali Riuniti di Bergamo

Bergamo, Bergamo, Italy

Divisione di Ematologia Spedali Civili di Brescia

Brescia, Brescia, Italy

USC Ematologia Azienda Ospedaliera Università Careggi

Florence, Firenze, Italy

UO Ematologia, Azienda Ospedaliera ULSS6

Vicenza, Vicenza, Italy

Countries

Italy

References

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.

Reference Type: RESULT

PMID: 19735261 (View on PubMed)

Other Identifiers

EUDRACT 2004-002280-24

Identifier Type: -

Identifier Source: secondary_id

NILG-HES1-03

Identifier Type: -

Identifier Source: org_study_id