E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Chronic Myeloid Leukemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009013 |
E.1.2 | Term | Chronic myeloid leukaemia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
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 |
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E.4 | Principal exclusion criteria |
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 |
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E.5 End points |
E.5.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 22 |
E.8.9.2 | In all countries concerned by the trial months | 0 |