ENESTfreedom
A Single-arm, Multicenter, Nilotinib Treatment-free Remission Study in Patients With BCR-ABL1 Positive Chronic Myelogenous Leukemia in Chronic Phase Who Have Achieved Durable Minimal Residual Disease (MRD) Status on First Line Nilotinib Treatment.
Phase 2N = 215NCT01784068
- Population
- Adults with Ph+ CML in chronic phase, MR4.5 and at least 2 years of frontline nilotinib
- Design
- Single-arm phase 2 trial. Patients with Ph+ CML in chronic phase and MR4.5 (BCR-ABL1 0.0032% or less on the International Scale) after at least 2 years of frontline nilotinib entered a 1-year nilotinib consolidation phase; those with sustained deep molecular response stopped treatment and entered the treatment-free remission (TFR) phase. Patients who lost major molecular response (BCR-ABL1 0.1% or less on the International Scale) restarted nilotinib.
- Primary endpoint
- TFR
- Arms
- Nilotinib consolidation, then discontinuation (experimental, n = 215): Frontline nilotinib continued for a 1-year consolidation phase, then stopped; restart on loss of major molecular response
- People
- Hochhaus A, senior author Saglio G
Show the numbers
| Endpoint | Analysis | Nilotinib consolidation, then discontinuation | Control | Effect |
|---|---|---|---|---|
| TFR190 patients who entered the TFR phase (215 entered the consolidation phase)Proportion of patients still in major molecular response or better 48 weeks after stopping nilotinib (the primary end point) | primaryHochhaus 2017 | 51.6% (44.2–58.9%) | — | 98 of 190 patients. Median duration of nilotinib before stopping was 43.5 months. 86 patients restarted nilotinib after loss of major molecular response; by the data cutoff 98.8% of them regained MMR and 88.4% regained MR4.5. Musculoskeletal pain-related events occurred in 24.7% of patients in the TFR phase (16.3% in the consolidation phase). The prespecified null hypothesis (TFR rate of 50% or less) could not be rejected because the lower limit of the 95% CI was below 50%. Data cutoff 30 November 2015, by which time all patients who entered the TFR phase had completed at least 48 weeks of TFR, entered the reinitiation phase or discontinued. |
| Endpoint | Analysis | Nilotinib consolidation, then discontinuation | Control | Effect |
|---|---|---|---|---|
| TFR190 patients who entered the TFR phase (215 entered the consolidation phase)Proportion of patients still in major molecular response or better 48 weeks after stopping nilotinib (the primary end point) | primaryHochhaus 2017 | 51.6% (44.2–58.9%) | — | 98 of 190 patients. Median duration of nilotinib before stopping was 43.5 months. 86 patients restarted nilotinib after loss of major molecular response; by the data cutoff 98.8% of them regained MMR and 88.4% regained MR4.5. Musculoskeletal pain-related events occurred in 24.7% of patients in the TFR phase (16.3% in the consolidation phase). The prespecified null hypothesis (TFR rate of 50% or less) could not be rejected because the lower limit of the 95% CI was below 50%. Data cutoff 30 November 2015, by which time all patients who entered the TFR phase had completed at least 48 weeks of TFR, entered the reinitiation phase or discontinued. |