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

Sponsor

University of Bologna (Other)

Overall Status

Unknown status

CT.gov ID

NCT00276926

Collaborator

Novartis (Industry)

Locations

Study Details

Study Description

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:

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.
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.
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.
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

Study Type:

Interventional

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 :

Mar 1, 2003

Outcome Measures

Primary Outcome Measures

Rate of complete response (CR) in all patients at 3rd month []

Secondary Outcome Measures

Duration of response (CR) []
Overall survival at 12th month []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Presence of primary or secondary HES
Not a candidate for allogeneic bone marrow transplantation.
ECOG performance score of 0, 1, 2 or 3 (Karnofsky performance score > 40%).
Life expectancy > 4 weeks.
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.
Age 18 years or greater.
Post-menopausal, surgically sterile, or taking effective contraception in female patients.
Documentation of written informed consent to participate in the trial.
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:

Patients with clear evidence of secondary hypereosinophilia.
Acute myeloblastic leukemia with inv(16) positive blast or
CBFb-MYH11 transcripts positive leukemia
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.
Treatment with any investigational agent within 4 weeks prior to study therapy.
Major surgeries within 4 weeks from study start or not fully recovered from any previous surgical procedure.
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
Presence of central nervous system (CNS) illness and involvement of disease.
Active uncontrolled bacterial infection.
Known human immunodeficiency virus (HIV) infection.
Grade 3 or 4 bleeding.
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.
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.
Pregnancy or breast-feeding.
Malabsorption syndromes

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna	Bologna	Italy	40138
2	Dipartimento di Medicina Interna - Università di Genova	Genova	Italy	16100
3	Dipartimento di Biochimica e Biotecnologie Mediche - Università degli Studi di Napoli "Federico II"	Napoli	Italy	80131
4	Divisione di Ematologia - Università degli Studi di Napoli "Federico II"	Napoli	Italy	80131
5	S.C. Medicina Interna II ed Ematologia - Laboratorio di Medicina Interna e Molecolare - A.O. San Luigi	Orbassano	Italy	10043
6	Divisione di Ematologia - IRCCS Policlinico S. Matteo	Pavia	Italy	27100
7	U.O. Ematologia - Dipartimento di Oncologia ed Ematologia, Presidio Ospedaliero di Ravenna	Ravenna	Italy	48100
8	U.O. Ematologia - Arcispedale Santa Maria Nuova	Reggio Emilia	Italy	42100
9	Cattedra di Ematologia - Università "Tor Vergata"	Roma	Italy	00133
10	Cattedra di Ematologia - Università "La Sapienza"	Roma	Italy	00161
11	Divisione di Ematologia - Casa Sollievo della Sofferenza	San Giovanni Rotondo	Italy	71013
12	U.O.C. Ematologia e Trapianti - Policlinico "Le Scotte"	Siena	Italy	53100
13	U.O. Medicina II Divisione - Ospedale Santa Chiara	Trento	Italy	38100
14	Clinica Ematologica - Policlinico Universitario	Udine	Italy	33100