E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic phase chronic myelogenous leukaemia (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 reduce the rate of adverse event observed in de novo CML in chronic phase patients treated with dasatinib 100 mg QD. |
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E.2.2 | Secondary objectives of the trial |
To compare the rate of treatment interruptions To compare the cumulative duration of dasatinib interruption. To compare the median dose of dasatinib administered during the first 12 months To compare the mean dose of dasatinib administered during the first 12 months To compare the cumulative rate of complete cytogenetic response at 6, 12 and 18 months and every 12 months thereafter To compare the cumulative rate of major molecular response at 3, 6, 12, 18 months and every 6 months thereafter. To compare the cumulative rate of complete molecular response at 3, 6, 12 and 18 months and every 6 months thereafter To compare the time to molecular response (major or complete) To analyse the relationship between peak plasmatic level (Cmax) and efficacy in the three arms To compare the progression free survival at 5 years in the three arms To compare the event free survival at 5 years in the three arms To compare the overall survival at 5 years in the three arms
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patient ≥ 18 years 2. ECOG Performance Status score 0-2 3. Philadelphia chromosome positive newly diagnosed chronic myelogenous leukaemia (≤ 3 months) in chronic phase. 4. Not previously treated except with hydroxyurea 5. Signed written inform consent 6. Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional ULN; ALT and AST ≤ 2.5 times the institutional upper limit of normal (ULN). 7. Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN. 8. 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 3. Pregnancy 4. Active malignancy 5. Uncontrolled or significant cardiovascular disease 6. Patients with QTc > 450 ms 7. Significant bleeding disorder unrelated to CML 8. Concurrent severe diseases which exclude the administration of therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Primary endpoint : The cumulative rate of significant adverse events defined by all grade fluid retention, all grade pleural effusion, haematological grade 3-4 adverse events related to dasatinib and/or all adverse event leading to dasatinib interruption within the first year of therapy. 2. Secondary endpoints : a. The rate of treatment interruptions in the three arms. b. The cumulative duration of dasatinib interruption during the first 12 months of therapy c. The median dose of dasatinib administered during the first 12 months of therapy d. The mean dose of dasatinib administered during the first 12 months of therapy e. Complete cytogenetic response at 6, 12 and 18 months and every 12 months thereafter in the three arms f. Major molecular response at 3, 6, 12 and 18 months and every 6 months thereafter defined by a standardized BCR-ABL/ABL ratio ≤0.1% in the three arms g. Complete molecular response 3, 6, 12 and 18 months and every 6 months thereafter defined by an undetectable BCR-ABL transcript at the sensitivity level of 10-5 in the three arms h. Time to molecular response (major or complete) i. Relationship between peak plasmatic level (Cmax) and efficacy in the three arms j. Relationship between through plasmatic level (Cmin) and efficacy in the three arms k. Progression free survival at 5 years in the three arms l. Event free survival at 5 years in the three arms
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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 | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 23 |
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 | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |