Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes

Overview

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.

Full Title of Study: “Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2007

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.

Interventions

  • 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.

Arms, Groups and Cohorts

  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Response rate

Secondary 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 15 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Northern Italy Leukemia Group
  • Provider of Information About this Clinical Study
    • Dr Renato Bassan, NILG
  • Overall Official(s)
    • Renato Bassan, MD, Principal Investigator, USC Ematologia Ospedali Riuniti di Bergamo

Citations Reporting on Results

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.

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