E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive 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 | 10054352 |
E.1.2 | Term | Chronic phase chronic myeloid leukemia |
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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 compare the best confirmed complete cytogenetic response (CCyR) rates within 12 months in newly diagnosed chronic phase CML subjects treated with dasatinib 100 mg QD versus imatinib 400 mg QD. |
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E.2.2 | Secondary objectives of the trial |
• To compare the following efficacy parameters within 12 months: major molecular response rate (MMR); major cytogenetic response rate (MCyR); complete hematologic response (CHR). • To compare the following study parameters at any time: Best overall MMR, CCyR, MCyR and CHR rate; Durations of and times to MMR, CCyR, MCyR and CHR; Progression-free survival (PFS) and overall survival (OS); Time to treatment failure (TTF). • To evaluate the toxicity profile for each treatment arm. • To explore the development of BCR-ABL point mutations in both treatment arms. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Subjects able to provide written informed consent. 2) Patients must have Ph+ CML in CP which is defined by the presence of all of the following criteria: < 15% blasts in peripheral blood and bone marrow. < 30% blasts plus promyelocytes in peripheral blood and bone marrow. < 20% basophils in the peripheral blood. ≥ 100 x 10E9/L platelets. No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly. Ph+ or variants must be demonstrated by BM cytogenetics. 3) Previously untreated chronic CML [less than 4 weeks (28 days) of imatinib are allowed provided the subject did not experience grade 3-4 hematologic or nonhematologic toxicity attributed to imatinib] 4) Subjects must be enrolled in this study within approximately 3 months (90 days) after the date of first being diagnosed with CML, based on cytogenetic test results of bone marrow, demonstrating the presence of the Philadelphia chromosome or variants of the (9;22) translocation. Subjects are allowed to have secondary chromosomal abnormalities (i.e., clonal evolution) in addition to the Philadelphia chromosome and remain eligible. 5) ECOG Performance Status (PS) Score 0 - 2. 6) Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (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) Men and women, ages 18 years and older. 9) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month (4 weeks) before and at least 1 month (4 weeks) after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. 10) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. |
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E.4 | Principal exclusion criteria |
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one month (4 weeks) before and for at least 1 month (4 weeks) after the last dose of study medication. 2) WOCBP using a prohibited contraceptive method (Not applicable for this study). 3) Women who are pregnant or breastfeeding. 4) Women with a positive pregnancy test at enrollment or prior to administration of study medication. 5) Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one month (4 weeks) after completion of study medication. 6) A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy. 7) Known pleural effusion at baseline. 8) Uncontrolled or significant cardiovascular disease, including any of the following: A myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure within 3 months; Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe); Prolonged QTcF interval > 450 msec on pre-entry ECG 9) History of significant bleeding disorder unrelated to CML, including: Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease); Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies). 10) Prior chemotherapy for peripheral stem cell mobilization. (Prior collection of unmobilized peripheral blood stem cells is permitted). 11) Prior or concurrent malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer; cervical carcinoma in situ; adequately treated Stage I or II cancer from which the subject is currently in complete remission; or any other cancer from which the subject has been disease-free for three years. 12) Evidence of digestive dysfunction that would prevent administration of study therapy by mouth. 13) Any prior treatment with interferon 14) Any prior treatment with dasatinib 15) Any other prior systemic treatments, with anti-CML activity [except for anagrelide, hydroxyurea (HU) or 4 weeks (28 days) of imatinib]. 16) Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes. Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is greater) prior to the first dose of study therapy. Amiodarone must be discontinued for at least 14 days prior to randomization. 17) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the rate of best confirmed CCyR within 12 months. CCyR will be assessed via cytogenetic analysis of bone marrow biopsy/aspirate specimens. Cytogenetic analysis will occur at the local institutions and be reported via CRF. Toxic effects will be assessed continuously and reported for all treated subjects. Adverse events and other symptoms will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
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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 | 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 | 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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 62 |
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 | 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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Last follow up visit of the last patient |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |