DESTINY
A Trial of De-escalation and Stopping Treatment in Chronic Myeloid Leukaemia Patients With Excellent Responses to Tyrosine Kinase Inhibitor Therapy
Phase 2N = 174NCT01804985
- Population
- Adults (18 years and older) with CML in first chronic phase, at least 3 years of TKI, in stable MR4 (BCR-ABL1:ABL1 below 0.01%) or in stable MMR but not MR4 for 12 months or longer
- Design
- Non-randomised phase 2 trial at 20 UK hospitals; interim analysis. Patients received half their standard TKI dose for 12 months (imatinib 200 mg daily, dasatinib 50 mg daily or nilotinib 200 mg twice daily). Molecular recurrence was defined as loss of MMR (BCR-ABL1:ABL1 ratio above 0.1%) on two consecutive samples. Primary endpoint of the interim analysis: the proportion of patients who lost MMR on de-escalation and regained MMR on TKI resumption.
- Arms
- MR4 cohort (experimental, n = 125): Half standard TKI dose for 12 months; stable MR4 at entry
- MMR cohort (experimental, n = 49): Half standard TKI dose for 12 months; stable MMR but not MR4 at entry
- People
- Clark RE, senior author Copland M
Molecular recurrenceHR 0.12
Show the numbers
| Endpoint | Analysis | MR4 cohort / MMR cohort | Control | Effect |
|---|---|---|---|---|
| Molecular recurrenceEvaluable patients: 121 in the MR4 cohort and 48 in the MMR cohort (the abstract states analyses were by intention to treat)Loss of MMR (BCR-ABL1:ABL1 ratio above 0.1%) on two consecutive samples during 12 months of half-dose TKI | interimClark 2017 | 2% | — | HR 0.12P=0.00073 of 121 evaluable patients in the MR4 cohort (2%; 90% CI 0.2 to 4.8) and 9 of 48 in the MMR cohort (19%; 90% CI 9.5 to 28.0). The hazard ratio of 0.12 has a 90% CI of 0.04 to 0.37 (not a 95% interval), so the interval is stated here and not in the interval field; it compares the MR4 cohort with the MMR cohort. Overall 12 of 174 patients (7%) had molecular recurrence, all regained MMR within 4 months of resuming full-dose TKI (median 77 days). Recurrence was unrelated to previous TKI or duration of TKI therapy. |
| Endpoint | Analysis | MR4 cohort / MMR cohort | Control | Effect |
|---|---|---|---|---|
| Molecular recurrenceEvaluable patients: 121 in the MR4 cohort and 48 in the MMR cohort (the abstract states analyses were by intention to treat)Loss of MMR (BCR-ABL1:ABL1 ratio above 0.1%) on two consecutive samples during 12 months of half-dose TKI | interimClark 2017 | 2% | — | HR 0.12P=0.00073 of 121 evaluable patients in the MR4 cohort (2%; 90% CI 0.2 to 4.8) and 9 of 48 in the MMR cohort (19%; 90% CI 9.5 to 28.0). The hazard ratio of 0.12 has a 90% CI of 0.04 to 0.37 (not a 95% interval), so the interval is stated here and not in the interval field; it compares the MR4 cohort with the MMR cohort. Overall 12 of 174 patients (7%) had molecular recurrence, all regained MMR within 4 months of resuming full-dose TKI (median 77 days). Recurrence was unrelated to previous TKI or duration of TKI therapy. |
Appears in
Sources
Clark RE, Polydoros F, Apperley JF, Milojkovic D, Pocock C, Smith G, et al. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematol. 2017;4(7):e310-e316.