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

Myeloproliferative Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00276926
• Other study ID #: HES0203
• Status: Recruiting
• Phase: Phase 2
• First received: January 12, 2006
• Last updated: September 14, 2009
• Start date: March 2003

Study information

• Verified date: September 2009
• Source: University of Bologna
• Contact: Giovanni Martinelli, MD
• Phone: +39 051 6363829
• Email: gmartino[@]alma.unibo.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines AgencyItaly: Ethics Committee
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

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

Intervention

Drug:
• STI571

Locations

Country	Name	City	State
Italy	Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli" Università degli Studi di Bologna	Bologna
Italy	Dipartimento di Medicina Interna - Università di Genova	Genova
Italy	Dipartimento di Biochimica e Biotecnologie Mediche - Università degli Studi di Napoli "Federico II"	Napoli
Italy	Divisione di Ematologia - Università degli Studi di Napoli "Federico II"	Napoli
Italy	S.C. Medicina Interna II ed Ematologia - Laboratorio di Medicina Interna e Molecolare - A.O. San Luigi	Orbassano
Italy	Divisione di Ematologia - IRCCS Policlinico S. Matteo	Pavia
Italy	U.O. Ematologia - Dipartimento di Oncologia ed Ematologia, Presidio Ospedaliero di Ravenna	Ravenna
Italy	U.O. Ematologia - Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Cattedra di Ematologia - Università "La Sapienza"	Roma
Italy	Cattedra di Ematologia - Università "Tor Vergata"	Roma
Italy	Divisione di Ematologia - Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	U.O.C. Ematologia e Trapianti - Policlinico "Le Scotte"	Siena
Italy	U.O. Medicina II Divisione - Ospedale Santa Chiara	Trento
Italy	Clinica Ematologica - Policlinico Universitario	Udine

Sponsors (2)

Lead Sponsor	Collaborator
University of Bologna	Novartis

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete response (CR) in all patients at 3rd month
Secondary	Duration of response (CR)
Secondary	Overall survival at 12th month