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 |
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 |
Main objective: Assessment of treatment-free remission (persistence of MMR) after sec-ond attempt of TKI discontinuation in patients who failed a relapsed in the EURO-SKI study or under EURO-SKI like conditions Patients must have received least three years of further TKI treatment of which the two last years should be dasatinib. The patients must have been in MR4 for at least one year.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: 1.Identification of clinical and biological factors correlating with the persistence of MMR or better after stopping TKI a second time. 2.Estimation of overall and progression free survival 3.Evaluation of medico-economic impact of stopping TKI a second time. 4.Time to re-achievement of MR4 after restart of therapy following a second molecular relapse 5.Assessment of incidence of any AEs (e.g. from treatment related musculoskeletal AE ) that arise after stopping TKI treatment a sec-ond time.
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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 |
1. Immunophenotyping of lymphocyte subsets. 2. Assessment of antileukemic cytotoxic T-cell responses. 3. Plasma cytokine profiling. 4. Functional assessments of NK and T cells. 5. Immunological monitoring-plasmacytoid DCs. 6. Evaluation of soluble CD62L levels and TACE. activity as relapse risk sensing tools. 7. TCR repertoire analysis by deep sequencing. 8. Kir genotyping. 9. Cytof-based Immune-phospho-flow cytometry
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E.3 | Principal inclusion criteria |
1.CML in CP under TKI treatment after failing a prior attempt to stop treatment within EURO-SKI or outside the study but according to EURO-SKI trial procedures. For the latter group this requires at least 3 years of TKI treatment (first line or second line due to intolerance to first line) before first stop, and MR4 for at least one year before stopping, 2.Treated with TKI for at least one year after having failed a prior at-tempt to stop TKI. Previous TKI can be any. 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 hematological relapse after first stop of TKI. 2.Previous AP/BC at any time in the history of the disease. 3.Restart of TKI without loss of MMR after first stop 4.Current participation in another clinical study. 5.Previous or planned allogeneic stem cell transplantation. 6.Patients with contra-in dications to dasatinib therapy due to comor-bidities. 7.Subjects with acute hepatitis B virus (HBV) infections. 8.Uncontrolled or significant cardiovascular disease. 9. Pulmonary arterial hypertension 9.Pleural or pericardial effusions of any grade at study entry 11. History of significant bleeding disorder unrelated to CML 12 .A third stopping attempt. |
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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 a second time (survival without loss of major molecular response, MMR, defined as BCR-ABL1 > 0.1% on IS at one time point). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 and 12 months after discontinuing TKI a second time. |
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E.5.2 | Secondary end point(s) |
Assessment of: 1.Number of patients who re-achieved stable MR4, and were offered study participation; proportion of patients who accept/refuse study participation. 2.Clinical and biological factors correlating with persistence of MMR or better after second TKI stop (BCR-ABL level before 2nd stop, Sokal score, gender, duration and type of TKI-treatment, duration of first TKI-stop, immunological biomarkers) 3.Overall and progression-free survival and the occurrence of a restart of TKI without prior molecular relapse. 4.Net treatment cost savings from the time off TKI therapy a second time considering also the more frequent PCR monitoring. 5.Time to reachievement of MR4 after second loss of MMR. 6.Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AE’s.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 years after stop of TKI therapy |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | 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 | No |
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 | No |
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 | 19 |
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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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 |