Study of STI571 in the Treatment of Patients With Idiopathic Hypereosinophilic Syndrome (HES) and Eosinophilic Leukemias

September 14, 2009 updated by: University of Bologna

Open Label Pilot Phase II Study of STI571 in the Treatment of Patients With Idiopathic Hypereosinophilic Syndrome (HES) and Eosinophilic Leukemias

The purpose of this study is to assess the clinical anti-proliferative activity of STI571 (Glivec®, Novartis, Pharma) in patients with HES defined as:

  1. Idiopathic Hypereosinophilic Syndrome (secondary HES), defined as a peripheral blood eosinophilia greater than 1,500 cells/µL for longer than 6 months, absence of other apparent aetiologies for eosinophilia and with or without signs and symptoms of organ involvement, irrespective to expression of any of imatinib targets (c-Kit receptor, PDGFR, bcr-abl receptor) on bone marrow cells.
  2. Familiar hypereosinophilia defined as a peripheral blood eosinophilia greater than 1,500 cells/µL for longer than 6 months, absence of other apparent aetiologies for eosinophilia and signs and symptoms of organ involvement, irrespective to expression of any of imatinib targets (c-Kit receptor, PDGFR, bcr-abl receptor) on bone marrow cells, and with a recognized or reported cases of hypereosinophilia in the patient's family.
  3. Chronic myeloproliferative disorder, defined as chronic eosinophilic leukemia (CEL) with the presence of blasts (>10%) in the bone marrow (BM), or the presence of immature eosinophils in different tissues, or an aggressive clinical course or the presence of clonal cytogenetic anomalies.
  4. Myeloproliferative disorder (MPD) with eosinophilia, eosinophilic leukemia or chronic myelomonocytic leukemia [myeloproliferative disorders/myelodysplastic syndromes (MPD/MDS)] with evidence of:

    • t(5;12)(q33;p13) by cytogenetic or fluorescent in situ hybridization (FISH) analysis, or
    • ETV6/TEL-PDGFRB fusion transcript by reverse transcription polymerase chain reaction (RT-PCR), or
    • PDGFRB disruption, assessed or suspected, by other translocations with additional partner genes (H4, HIP1, CEV14 and Rab5) 5, or
    • MPD/MDS who have constitutive activation of the gene for platelet-derived growth factor receptor beta (PDGFRB) 6 by point mutations

Study Overview

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Bologna, Italy, 40138
        • Recruiting
        • Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna
        • Sub-Investigator:
          • Michela Rondoni, MD
        • Sub-Investigator:
          • Pier Paolo Piccaluga, MD, PhD
      • Genova, Italy, 16100
        • Recruiting
        • Dipartimento di Medicina Interna - Università di Genova
        • Contact:
      • Napoli, Italy, 80131
        • Recruiting
        • Dipartimento di Biochimica e Biotecnologie Mediche - Università degli Studi di Napoli "Federico II"
        • Contact:
      • Napoli, Italy, 80131
        • Recruiting
        • Divisione di Ematologia - Università degli Studi di Napoli "Federico II"
        • Contact:
        • Principal Investigator:
          • Bruno Rotoli, MD
        • Sub-Investigator:
          • Lucio Catalano, MD
      • Orbassano, Italy, 10043
        • Recruiting
        • S.C. Medicina Interna II ed Ematologia - Laboratorio di Medicina Interna e Molecolare - A.O. San Luigi
        • Contact:
        • Contact:
        • Principal Investigator:
          • Giuseppe Saglio, MD
        • Sub-Investigator:
          • Daniela Cilloni, MD
      • Pavia, Italy, 27100
        • Recruiting
        • Divisione di Ematologia - IRCCS Policlinico S. Matteo
        • Contact:
        • Principal Investigator:
          • Mario Lazzarino, MD
        • Sub-Investigator:
          • Serena Merante, MD
      • Ravenna, Italy, 48100
        • Recruiting
        • U.O. Ematologia - Dipartimento di Oncologia ed Ematologia, Presidio Ospedaliero di Ravenna
        • Contact:
        • Sub-Investigator:
          • Eliana Zuffa, MD
      • Reggio Emilia, Italy, 42100
        • Recruiting
        • U.O. Ematologia - Arcispedale Santa Maria Nuova
        • Contact:
        • Sub-Investigator:
          • Paolo Avanzini, MD
      • Roma, Italy, 00133
        • Recruiting
        • Cattedra di Ematologia - Università "Tor Vergata"
        • Contact:
        • Sub-Investigator:
          • Francesco Buccisano, MD
      • Roma, Italy, 00161
        • Recruiting
        • Cattedra di Ematologia - Università "La Sapienza"
        • Contact:
        • Principal Investigator:
          • Franco Mandelli, MD
        • Sub-Investigator:
          • Giuliana Alimena, MD
      • San Giovanni Rotondo, Italy, 71013
        • Recruiting
        • Divisione di Ematologia - Casa Sollievo della Sofferenza
        • Contact:
          • Pellegrino Musto, MD
          • Phone Number: +39 0882410539
          • Email: p.musto@tin.it
        • Sub-Investigator:
          • Pellegrino Musto, MD
      • Siena, Italy, 53100
        • Recruiting
        • U.O.C. Ematologia e Trapianti - Policlinico "Le Scotte"
        • Contact:
        • Sub-Investigator:
          • Monica Bocchia, MD
      • Trento, Italy, 38100
        • Recruiting
        • U.O. Medicina II Divisione - Ospedale Santa Chiara
        • Contact:
        • Principal Investigator:
          • Mauro Pedrazzoli, MD
        • Sub-Investigator:
          • Paolo Vivaldi, MD
        • Sub-Investigator:
          • Silvia Cerù, MD
        • Sub-Investigator:
          • Anna Guella, MD
      • Udine, Italy, 33100
        • Recruiting
        • Clinica Ematologica - Policlinico Universitario
        • Contact:
        • Sub-Investigator:
          • Mario Tiribelli, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Presence of primary or secondary HES
  2. Not a candidate for allogeneic bone marrow transplantation.
  3. ECOG performance score of 0, 1, 2 or 3 (Karnofsky performance score > 40%).
  4. Life expectancy > 4 weeks.
  5. Adequate hepatic and renal function, as defined by serum transaminases < 2.5x upper limits of normal (ULN), bilirubin < 1.5x ULN, and creatinine < 1.5x ULN.
  6. Age 18 years or greater.
  7. Post-menopausal, surgically sterile, or taking effective contraception in female patients.
  8. Documentation of written informed consent to participate in the trial.
  9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

The presence of any of the following will exclude a subject from study enrollment:

  1. Patients with clear evidence of secondary hypereosinophilia.
  2. Acute myeloblastic leukemia with inv(16) positive blast or
  3. CBFb-MYH11 transcripts positive leukemia
  4. Lack of recovery from the acute toxic effects of previous chemotherapy [to common toxicity criteria (CTC) grade > 1] with the exception of chemotherapy-induced alopecia.
  5. Treatment with any investigational agent within 4 weeks prior to study therapy.
  6. Major surgeries within 4 weeks from study start or not fully recovered from any previous surgical procedure.
  7. Presence of any medical or psychiatric condition which may limit full compliance with the study or increase the risk associated with study participation or study drug administration, including but not limited to
  8. Presence of central nervous system (CNS) illness and involvement of disease.
  9. Active uncontrolled bacterial infection.
  10. Known human immunodeficiency virus (HIV) infection.
  11. Grade 3 or 4 bleeding.
  12. Significant cardiovascular disease (i.e., uncontrolled arrhythmias, unstable angina), or a major thromboembolic event (myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, or non-catheter-related deep-vein thrombosis) in the last 6 months. Due to the low cardiac toxicity profile of Glivec, it is not considered an exclusion criterion if the presence of severe complications to the viscera, among which cardiopathies, and in particular endomyocardial fibrosis, is due or considered to be due to HES.
  13. Increased blood eosinophil counts due to the presence of physician-diagnosed asthma. However, due to low pulmonary toxicity profile of Glivec, it is not considered an exclusion criterion, if HES is associated with asthma, and the presence of severe complications damaging the lungs, are considered due to HES.
  14. Pregnancy or breast-feeding.
  15. Malabsorption syndromes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Rate of complete response (CR) in all patients at 3rd month

Secondary Outcome Measures

Outcome Measure
Duration of response (CR)
Overall survival at 12th month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2003

Study Registration Dates

First Submitted

January 12, 2006

First Submitted That Met QC Criteria

January 12, 2006

First Posted (Estimate)

January 13, 2006

Study Record Updates

Last Update Posted (Estimate)

September 15, 2009

Last Update Submitted That Met QC Criteria

September 14, 2009

Last Verified

September 1, 2009

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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