E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
newly-diagnosed chronic-phase Chronic myeloid leukaemia (CML) |
|
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 |
|
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 compare 5-year Event Free Survival (EFS) between the two treatment arms. The study is powered to demonstrate superiority of the dasatinib arm over the imatinib arm. |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the rate of complete cytogenetic response after two years of study therapy in each of the treatment arms and the cumulative incidence of such responses with each of the regimens. The study is powered to demonstrate superiority of the dasatinib arm over the imatinib arm. 2. To compare the treatment faliure rates (TFR) at 5 years between the two arms of the study 3. To compare the rates of complete haematologic response (CHR) in patients treated with these regimens in each of the treatment arms 4. To compare the level of 'molecular response (BCR-ABL/ABL ratio by real time PCR) in each of the treatment arms 5. To compare the tolerability between the regimens. This will in part be incorporated into the treatment failure assessment. 6. To assess quality of life between the regimens 7. To assess the broad comparative costs between the regimens 8. To compare overall survival at 2 and 5 years |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients 18 years of age or older. 2. Patients must have all of the following: i) be enrolled within 3 months of initial diagnosis of CML-CP (date of initial diagnosis is the date of first cytogenetic analysis), ii) cytogenetic confirmation of the Philadelphia chromosome or variants of (9;22) translocations; patients may have secondary chromosomal abnormalities in addition to the Philadelphia chromosome. iii) (a) < 15% blasts in peripheral blood and bone marrow; (b) < 30% blasts plus promyelocytes in peripheral blood and bone marrow; (c) < 20% basophils in peripheral blood, (d) a platelet count of 100 x 109/L platelets or higher iv) no evidence of extramedullary leukaemic involvement, with the exception of hepatosplenomegaly. 3. Written voluntary informed consent. |
|
E.4 | Principal exclusion criteria |
1. Patients with Ph-negative, BCR-ABL-positive, disease are NOT eligible for the study. 2. Any prior treatment for CML with: any tyrosine kinase inhibitor (eg imatinib, dasatinib, nilotinib); busulphan; interferon-alpha; homoharringtonine; cytosine arabinoside; any other investigational agents (hydroxyurea and anagrelide are the only drugs permitted). NB patients will be ineligible for the study if they have received ANY prior therapy with interferon-alpha or imatinib. NO exceptions. 3. Patients who received prior chemotherapy, including regimens used in peripheral blood progenitor cells (PBPCs) mobilisation for haematopoietic progenitor-cell transplantation. (It is allowable to collect unmobilised PBPCs at diagnosis.) 4. Patient who have had any form of prior haemopoietic stem cell transplant, either autograft or allograft. 5. Patients with an ECOG Performance Status Score of 3 or greater. 6. Patients with serum bilirubin, SGOT/AST,! SGPT/ALT, or creatinine concentrations > 2.0 x the institutional upper limit of the normal range (IULN). 7. Patients with International normalised ratio (INR) or partial thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulants. 8. Patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina, or Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria. 9. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required. 10. Patients who have undergone major surgery within 4 weeks of Study Day 1, or who have not recovered from prior major surgery. 11. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to Study Day 1, and (d) male or female of childbearing potential unwilling to use barrier contr! aceptive precautions throughout the trial (postmenopausal women must b e amenorrheaic for at least 12 months to be considered of non-childbearing potential). 12. Patients with a history of another malignancy either currently or within the past five years, with the exception of basal cell skin carcinoma or cervical carcinoma in situ. 13. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To compare 5-year Event Free Survival (EFS) between the two treatment arms. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 130 |
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
|
The end of the study for each individual patient is defined as date on which the patient reaches study visit 15 (60 months on study) unless the patient has discontinued prematurely before reaching visit 15. The end of the study is defined as the date on which the last patient continuing in the study reaches the last visit 15. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
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 |