Efficacy of Imatinib Mesylate in Hypereosinophilic Syndromes (NILG-HES1-03)

Therapeutic and Biological Effects of Imatinib Mesylate in Primary Hypereosinophilic Syndromes

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.

Study Overview

• Status: Completed
• Conditions: Hypereosinophilic Syndrome; Chronic Eosinophilic Leukemia; Chronic Idiopathic Hypereosinophilia
• Intervention / Treatment: Drug: Imatinib

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 Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24128
    • USC Ematologia Ospedali Riuniti di Bergamo
  • Brescia, Italy
    • Divisione di Ematologia Spedali Civili di Brescia
  • Firenze, Italy, 50134
    • USC Ematologia Azienda Ospedaliera Università Careggi
  • Vicenza, Italy, 36100
    • UO Ematologia, Azienda Ospedaliera ULSS6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate

Secondary Outcome Measures

Outcome Measure
Time to response
Safety: Adverse events and serious adverse events
Diagnostic profile of Imatinib-responsive cases
Duration of responses following drug withdrawal after 12 weeks

Collaborators and Investigators

• Sponsor: Northern Italy Leukemia Group
• Investigators: Principal Investigator: Renato Bassan, MD, USC Ematologia Ospedali Riuniti di Bergamo

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: November 6, 2008
• First Submitted That Met QC Criteria: November 6, 2008
• First Posted (Estimate): November 7, 2008

Study Record Updates

• Last Update Posted (Estimate): December 29, 2010
• Last Update Submitted That Met QC Criteria: December 28, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: Response; Imatinib; Hypereosinophilic syndrome (HES); chronic eosinophilic leukaemia (CEL); chronic idiopathic hypereosinophilia (CIH); Timing to response
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Hematologic Diseases; Leukocyte Disorders; Eosinophilia; Syndrome; Hypereosinophilic Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: NILG-HES1-03; EUDRACT 2004-002280-24