A pilot Phase II study of PHA-739358 in patients with Chronic Myeloid Leukemia relapsing on Gleevec or c-ABL therapy - ND
- Conditions
- Treatment of Chronic Myeloid LeukemiaMedDRA version: 9.1Level: LLTClassification code 10009013Term: Chronic myeloid leukaemia
- Registration Number
- EUCTR2006-006881-40-IT
- Lead Sponsor
- ERVIANO MEDICAL SCIENCES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 16
1.Patients with CML in chronic, accelerated or blast crisis phases , confirmed by bone marrow biopsy within 14 days of enrollment, relapsing on Gleevec or c-ABL therapy and preferably / 40 with T315I mutation in BCR-ABL kinase 2.Prior chemoimmunotherapy must have been completed 2 weeks before study treatment start. Treatment with hydroxyureas should be discontinued 1 day before initiating dosing with PHA-739358. 3.Age 18 years or greater 4.ECOG performance status of / 2 5.Normal blood pressure / 140/90 mmHg with or without hypertension treatment for at least one week 6.Adequate hepatic and renal function, as defined by serum transaminases / 2.5x ULN, bilirubin / 1.5x ULN, and creatinine / 1.5x ULN Grade 1 7.All acute toxic effects excluding alopecia of any prior therapy must have resolved to NCI CTCAE version 3.0 Grade / 1 8.Personally signed and dated IRB-approved informed consent form indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts 9.Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Major surgeries within 4 weeks from study treatment start or not fully recovered from any previous surgical procedure 2.Presence of central nervous system CNS leukemia 3.Active uncontrolled infection 4.Known history of human immunodeficiency virus HIV infection 5.Grade 3 or 4 bleeding 6.Abnormal LVEF 40 by TTE or 45 by MUGA scan performed within the last 2 weeks 7.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 8.Pregnancy or breast-feeding. Female patients must agree to avoid becoming pregnant during the study and in the following 90 days after the end of the treatment, be surgically sterile or be postmenopausal. Male patients must agree to use effective contraception and have no intention to father a child for 180 days after the end of treatment, or be surgically sterile. The definition of effective contraception will be based on the judgment of the principal Investigator or a designated associate 9.Presence of any medical/psychiatric condition or laboratory abnormalities which may limit full compliance with the study, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To explore the clinical efficacy of PHA-739358 in the targeted population of CML patients in terms of hematological response lasting at least 4 weeks To explore the clinical efficacy of PHA-739358 in terms of cytogenetic response in bone marrow, when it applies. To explore the response depending on status of T315I mutation in BCR-ABL kinase.;Secondary Objective: To explore the safety profile of PHA-739358 in CML To explore the pharmacokinetics profile of PHA-739358 and its N-oxide metabolite PHA-816359 in plasma To explore the modulation of histone H3 and CRKL phosphorylation after PHA-739358 administration To explore the relationship between PHA-739358 levels in plasma and the modulation of histone H3 and CRKL phosphorylation;Primary end point(s): Antileukemic response assessed as Complete Hematological Response CHR ; No Evidence of Leukemia NEL , Return to Chronic Phase RTC .Cytogenetic response assessed in bone marrow as Complete, Partial or Minor
- Secondary Outcome Measures
Name Time Method