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

Study Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hypereosinophilic Syndrome; Chronic Eosinophilic Leukemia (CEL); Myeloproliferative Disorders	Drug: STI571	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Official Title:	Open Label Pilot Phase II Study of STI571 in the Treatment of Patients With Idiopathic Hypereosinophilic Syndrome (HES) and Eosinophilic Leukemias
Study Start Date :	March 2003

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Rate of complete response (CR) in all patients at 3rd month

Secondary Outcome Measures :

1. Duration of response (CR)
2. Overall survival at 12th month

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Contacts

Contact: Giovanni Martinelli, MD	+39 051 6363829	gmartino@alma.unibo.it
Contact: Livia Galletti, PhD	+39 051 6363829	acute@med.unibo.it

Locations

Italy
Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna	Recruiting
Bologna, Italy, 40138
Principal Investigator: Giovanni Martinelli, MD
Sub-Investigator: Michela Rondoni, MD
Sub-Investigator: Pier Paolo Piccaluga, MD, PhD
Sub-Investigator: Stefania Paolini, MD
Dipartimento di Medicina Interna - Università di Genova	Recruiting
Genova, Italy, 16100
Contact: Marco Gobbi, MD +39 010 3532395 gobbi@unige.it
Principal Investigator: Marco Gobbi, MD
Dipartimento di Biochimica e Biotecnologie Mediche - Università degli Studi di Napoli "Federico II"	Recruiting
Napoli, Italy, 80131
Contact: Fabrizio Pane, MD + 39 081 7463135 fabpane@unina.it
Principal Investigator: Fabrizio Pane, MD
Divisione di Ematologia - Università degli Studi di Napoli "Federico II"	Recruiting
Napoli, Italy, 80131
Contact: Lucio Catalano, MD + 39 081 7462068 lcatalan@unina.it
Principal Investigator: Bruno Rotoli, MD
Sub-Investigator: Lucio Catalano, MD
S.C. Medicina Interna II ed Ematologia - Laboratorio di Medicina Interna e Molecolare - A.O. San Luigi	Recruiting
Orbassano, Italy, 10043
Contact: Emanuela Messa, MD +39 0119026721 emanuelamessa@yahoo.it
Contact: Daniela Cilloni, MD +39 0119026610 daniela.cilloni@unito.it
Principal Investigator: Giuseppe Saglio, MD
Sub-Investigator: Emanuela Messa, MD
Sub-Investigator: Daniela Cilloni, MD
Divisione di Ematologia - IRCCS Policlinico S. Matteo	Recruiting
Pavia, Italy, 27100
Contact: Serena Merante, MD +39 0382502250 s.merante@smatteo.pv.it
Principal Investigator: Mario Lazzarino, MD
Sub-Investigator: Serena Merante, MD
U.O. Ematologia - Dipartimento di Oncologia ed Ematologia, Presidio Ospedaliero di Ravenna	Recruiting
Ravenna, Italy, 48100
Contact: Eliana Zuffa, MD +39 0544285752 e.zuffa@ausl.ra.it
Principal Investigator: Alfonso Zaccaria, MD
Sub-Investigator: Eliana Zuffa, MD
U.O. Ematologia - Arcispedale Santa Maria Nuova	Recruiting
Reggio Emilia, Italy, 42100
Contact: Paolo Avanzini, MD +39 0522296681 paolo.avanzini@asmn.re.it
Principal Investigator: Luigi Gugliotta, MD
Sub-Investigator: Paolo Avanzini, MD
Cattedra di Ematologia - Università "Tor Vergata"	Recruiting
Roma, Italy, 00133
Contact: Francesco Buccisano, MD +39 06 20902674 francesco.buccisano@uniroma2.it
Principal Investigator: Sergio Amadori, MD
Sub-Investigator: Francesco Buccisano, MD
Cattedra di Ematologia - Università "La Sapienza"	Recruiting
Roma, Italy, 00161
Contact: Giuliana Alimena, MD +39 06857951 alimena@bce.med.uniroma1.it
Principal Investigator: Franco Mandelli, MD
Sub-Investigator: Giuliana Alimena, MD
Divisione di Ematologia - Casa Sollievo della Sofferenza	Recruiting
San Giovanni Rotondo, Italy, 71013
Contact: Pellegrino Musto, MD +39 0882410539 p.musto@tin.it
Principal Investigator: Angelo Michele Carella, MD
Sub-Investigator: Pellegrino Musto, MD
U.O.C. Ematologia e Trapianti - Policlinico "Le Scotte"	Recruiting
Siena, Italy, 53100
Contact: Monica Bocchia, MD +39 0577586798 bocchia@unisi.it
Principal Investigator: Francesco Lauria, MD
Sub-Investigator: Monica Bocchia, MD
U.O. Medicina II Divisione - Ospedale Santa Chiara	Recruiting
Trento, Italy, 38100
Contact: Paolo Vivaldi, MD +39 0461903307 paolo.vivaldi@tn.it
Principal Investigator: Mauro Pedrazzoli, MD
Sub-Investigator: Paolo Vivaldi, MD
Sub-Investigator: Silvia Cerù, MD
Sub-Investigator: Anna Guella, MD
Clinica Ematologica - Policlinico Universitario	Recruiting
Udine, Italy, 33100
Contact: Mario Tiribelli, MD +39 0432559662 mtiribelli@hotmail.com
Principal Investigator: Renato Fanin, MD
Sub-Investigator: Mario Tiribelli, MD

Sponsors and Collaborators

University of Bologna

Novartis

Investigators

Principal Investigator:	Michele Baccarani, MD	Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

ClinicalTrials.gov Identifier:	NCT00276926 History of Changes
Other Study ID Numbers:	HES0203
First Posted:	January 13, 2006
Last Update Posted:	September 15, 2009
Last Verified:	September 2009

Keywords provided by University of Bologna:

Hypereosinophilic Syndrome; Eosinophilic leukemias; STI571 (Gleevec); PDGF receptor alpha	Familiar hypereosinophilia; Myeloproliferative disorder (MPD) with eosinophilia; myeloproliferative disorders/myelodysplastic syndromes

Additional relevant MeSH terms:

Hypereosinophilic Syndrome; Syndrome; Leukemia; Myeloproliferative Disorders; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases	Hematologic Diseases; Eosinophilia; Leukocyte Disorders; Imatinib Mesylate; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action