E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Myeloid Leukemia, a type of chronic blood cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
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 |
Assessment of treatment-free remission (persistence of major molecular response,MMR) after attempt of TKI discontinuation in patients who have been treated in the Nord CML 007 study. Patients must have received at least Three years of TKI treatment. The patients must have been in MR4 for at least one year.
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E.2.2 | Secondary objectives of the trial |
Identification of clinical and biological factors correlating with the persistence of MMR or better after stopping TKI .
Estimation of overall and progression free survival.
Time to re-achievement of MR4 after restart of therapy following a molecular relapse.
Assessment of incidence of any AEs (e.g. treatment related muscu-loskeletal AE) that arise after stopping TKI treatment .
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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 |
Scientific sub studies of the immune system and stem cell biology |
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E.3 | Principal inclusion criteria |
1. CML in chronic phase under TKI treatment in the Nord CML007 study
2. Treated with TKI for at least three years and in MR4 for at least one year.
3. Typical BCR/ABL1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis or later during the disease course.
4. 18 years or older.
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E.4 | Principal exclusion criteria |
1. Previous AP/BC at any time in the history of the disease.
2. Current participation in another clinical study.
3. Planned allogeneic stem cell transplantation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients maintaining MMR at 6 and 12 months after discontinuing TKI (survival without loss of major molecular response, MMR, defined as BCR-ABL1 >0.1% on IS in two consecutive samples. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Assessment of:
1. Clinical and biological factors correlating with persistence of MMR or better after TKI stop (BCR-ABL level before 2nd stop, Sokal score, gender, duration and type of TKI-treatment, immunological biomarkers)
2. Number of patients who achieve stable MR4, and can be offered study participation; overall and progression-free survival and the occurrence of a restart of TKI without prior molecular relapse.
3. Time to re-achievement of MR4 after loss of MMR.
4. Adverse events related to TKI stop, clinical and biological factors correlated to development of these AEs.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical factors: baseline
Immunological biomarkers: baseline, 1 month, 6 months and at relapse when applicable
Overall and progression-free survial: month 36
Time to re-achievement of MR4: 12 months after relapse
Edverse events: month 36 |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life analysis is included
Several measurements of lymphocytes and stem cells for identification of good markers |
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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 | No |
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 |
Comparison with historical controls |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | No |
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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Patients are followed for Three years after TKI discontinuation. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |