E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Phase Chronic myelogenous leukemia (CP CML) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evalutate the efficacy and the feasibility of the adaptation of imatinib daily dose based on imatinib mesylate (Gleevec®, Laboratoires Novartis Pharma) plasmatic trough level in term of major molecular response at 12 months. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the cumulative rate of major cytogenetic response at 6 and12 months. To evaluate the cumulative rate of complete cytogenetic response at 6 and 12 months To evaluate the cumulative rate of complete molecular response at 3, 6, 9 and 12 months To evaluate the time to molecular response (major or complete) in each cohort To evaluate the tolerance of optimized imatinib therapy. To evaluate overall survival, progression free survival and event free survival at 5 years. To evaluate intra patient variations of imatinib dosage To correlate the imatinib trough level to the daily dose of imatinib To evaluate the impact of imatinib metabolites on efficacy and tolerance
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub study 1: SNPs polymorphisms associated to the major molecular response rate at 12 months in patients with CP CML and treated with imatinib. Objectives: The primary objective of this work is to identify SNPs polymorphisms associated to the major molecular response rate at 12 months in patients with CP CML and treated with imatinib as front line therapy. The secondary objectives are to correlate the SNPs polymorphism to the criteria of response defined par the European Leukemia Net, to the safety profil of imatinib, to the event free survival. We will also compare the SNPs profiles obtained with imatinib in order to identify key genes involved in the response to tyrosine kinase inhibitors |
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E.3 | Principal inclusion criteria |
1. Male or female patient ≥ 18 years 2. Philadelphia chromosome positive newly diagnosed chronic myelogenous leukaemia (≤ 4 months) in first chronic phase. 3. Not previously treated with tyrosine kinase inhibitors other than imatinib 4. Prior treatment with imatinib during less than 6 weeks 5. Signed written inform consent 6. Women of childbearing potential (WOCBP) must be using an adequate method of contraception
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E.4 | Principal exclusion criteria |
1. Patients with BCR-ABL positive, Philadelphia negative CML 2. Patient previously treated with TKI other than imatinib 3. Pregnancy 4. Active malignancy 5. Concurrent severe diseases which exclude the administration of therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
a. The major molecular response rate at 12 months in cohort 1. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 30 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |