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

NCT ID: NCT00276926

Last Updated: 2009-09-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-03-31

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

Conditions

Hypereosinophilic Syndrome; Chronic Eosinophilic Leukemia (CEL); Myeloproliferative Disorders

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Interventions

STI571

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

University of Bologna

OTHER

Sponsor Role: lead

Principal Investigators

Michele Baccarani, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna

Locations

Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna

Bologna, , Italy

Site Status: RECRUITING

Dipartimento di Medicina Interna - Università di Genova

Genova, , Italy

Site Status: RECRUITING

Dipartimento di Biochimica e Biotecnologie Mediche - Università degli Studi di Napoli "Federico II"

Napoli, , Italy

Site Status: RECRUITING

Divisione di Ematologia - Università degli Studi di Napoli "Federico II"

Napoli, , Italy

Site Status: RECRUITING

S.C. Medicina Interna II ed Ematologia - Laboratorio di Medicina Interna e Molecolare - A.O. San Luigi

Orbassano, , Italy

Site Status: RECRUITING

Divisione di Ematologia - IRCCS Policlinico S. Matteo

Pavia, , Italy

Site Status: RECRUITING

U.O. Ematologia - Dipartimento di Oncologia ed Ematologia, Presidio Ospedaliero di Ravenna

Ravenna, , Italy

Site Status: RECRUITING

U.O. Ematologia - Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status: RECRUITING

Cattedra di Ematologia - Università "Tor Vergata"

Roma, , Italy

Site Status: RECRUITING

Cattedra di Ematologia - Università "La Sapienza"

Roma, , Italy

Site Status: RECRUITING

Divisione di Ematologia - Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Site Status: RECRUITING

U.O.C. Ematologia e Trapianti - Policlinico "Le Scotte"

Siena, , Italy

Site Status: RECRUITING

U.O. Medicina II Divisione - Ospedale Santa Chiara

Trento, , Italy

Site Status: RECRUITING

Clinica Ematologica - Policlinico Universitario

Udine, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Giovanni Martinelli, MD

Role: CONTACT

gmartino@alma.unibo.it

+39 051 6363829

Livia Galletti, PhD

Role: CONTACT

acute@med.unibo.it

+39 051 6363829

Facility Contacts

Marco Gobbi, MD

Role: primary

gobbi@unige.it

+39 010 3532395

Fabrizio Pane, MD

Role: primary

fabpane@unina.it

+ 39 081 7463135

Lucio Catalano, MD

Role: primary

lcatalan@unina.it

+ 39 081 7462068

Emanuela Messa, MD

Role: primary

emanuelamessa@yahoo.it

+39 0119026721

Daniela Cilloni, MD

Role: backup

daniela.cilloni@unito.it

+39 0119026610

Serena Merante, MD

Role: primary

s.merante@smatteo.pv.it

+39 0382502250

Eliana Zuffa, MD

Role: primary

e.zuffa@ausl.ra.it

+39 0544285752

Paolo Avanzini, MD

Role: primary

paolo.avanzini@asmn.re.it

+39 0522296681

Francesco Buccisano, MD

Role: primary

francesco.buccisano@uniroma2.it

+39 06 20902674

Giuliana Alimena, MD

Role: primary

alimena@bce.med.uniroma1.it

+39 06857951

Pellegrino Musto, MD

Role: primary

p.musto@tin.it

+39 0882410539

Monica Bocchia, MD

Role: primary

bocchia@unisi.it

+39 0577586798

Paolo Vivaldi, MD

Role: primary

paolo.vivaldi@tn.it

+39 0461903307

Mario Tiribelli, MD

Role: primary

mtiribelli@hotmail.com

+39 0432559662

Other Identifiers

HES0203

Identifier Type: -

Identifier Source: org_study_id