E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) |
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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 establish whether 800 mg Gleevec/Glivec (as 400 mg bid) improves efficacy in newly diagnosed, previously untreated CML-CP patients as compared to 400 mg by the evaluation of the rate of molecular response at 12 months as measured by log reduction of Bcr-Abl transcript as detected by RT-PCR |
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E.2.2 | Secondary objectives of the trial |
(for full list see protocol) •To determine the rate of hematologic response •To determine the rate of complete cytogenetic response (CCyR) •To evaluate the time to (CCyR), molecular response, and complete molecular response •To compare the percentage of patients with a ≥ 3 log reduction in Bcr-Abl transcripts and with undetectable levels at 12 months and yearly thereafter •To evaluate progression-free survival (PFS) at 5 years •To evaluate the safety profile of Gleevec/Glivec when given at 800 mg daily administered as 400 mg bid •To evaluate the actual dose-intensity delivered amongst the two treatment arms •To validate molecular response (MR) as a prognostic factor for time-to-progression (TTP) •To evaluate quality of life (QoL) and healthcare resource utilization •To determine the pharmacokinetic characteristics following 400 mg versus 800 mg •To investigate tumor-specific mutations |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Ability to provide written informed consent prior to participation to the study. 2. Male or female patients ≥ 18 and ≤ 75 years of age 3. Patients within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis) 4. Diagnosis of chronic myelogenous leukemia in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Bcr-Abl 5. Documented chronic phase CML as defined by: • < 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 109/L (≥ 100,000 /mm3) platelets • No evidence of extramedullary leukemic involvement, with the exception of hepatospenomegaly 6. Adequate end organ function as defined by: • total bilirubin < 1.5 x ULN • SGOT and SGPT < 2.5 x UNL • creatinine < 1.5 x ULN 7. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug |
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E.4 | Principal exclusion criteria |
1. Patients in late chronic phase, accelerated phase, or blastic phase are excluded 2. Patients who have received other investigational agents 3. Patients who received Gleevec/Glivec for any duration prior to study entry, with the exception of those patients successfully completing [CSTIA2107] study immediately prior to the participation in this study 4. Patient received any treatment for CML prior to study entry for longer than 1 month with the exception of hydroxyurea and/or anagrelide 5. Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention 6. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). 7. Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes, chronic renal disease) 8. Patient previously received radiotherapy to ≥ 25% of the bone marrow 9. Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery 10. Patients with an ECOG Performance Status Score ≥ 3 11. Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulants 12. Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required 13. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent 14. Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the rate of molecular response (MR) at 12 months as measured by log reduction of Bcr-Abl transcript as detected by RT-PCR |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | 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) | 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.8.5 | The trial involves multiple Member States | Yes |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 5 |