STEPWISE DOSE ESCALATION METHOD FOR NILOTINIB STOP TRIAL IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA (STEP STOP TRIAL) : A MULTICENTER PHASE 2 TRIAL
(Abstract release date: 05/19/16)
EHA Library. Ota K. 06/09/16; 134725; PB1825
Dr. Ken Ota
Contributions
Contributions
Abstract
Abstract: PB1825
Type: Publication Only
Background
The STIM trial, stood in innovative point of view, indicate that imatinib may be successfully stopped in patients with deep molecular responses. Subsequently, the feasibility of various TKIs discontinuation trials have been investigated. The most important factor in TKIs discontinuation trials is the molecular response of BCR-ABL. The molecular response affected by many factors, such as Sokal score, percentage of basophil, additional chromosome anomaly and so on. Another important factor for the success of TKIs stop study is adverse events of TKIs itself. Several patients are not able to continue the TKIs by the adverse events.
Aims
Stepwise dose escalation method of NIL improved the proportion of patients who had treatment free Remission or not. A prospective, multicenter, single-arm phase 2 trial was conducted.
Methods
The Stepwise Dose Escalation Method for Nilotinib Stop trial in Patients with Chronic Myeloid Leukemia (Step Stop trial) was a prospective, multicenter, single-arm phase 2 trial. Adult CML-CP patients with newly diagnosed or experienced TKIs (imatinib, dasatinib or nilotinib) was enrolled. The first half of this study was “stepwised induction (achieve CMR) and consolidation (for 2 years) phase”, stepwise dose escalation of NIL was conducted to avoid discontinuation of NIL by the adverse events. And the second half was “stop and monitoring phase”.Eligible patients were administered nilotinib with stepwise dose escalation method, i.e. 150mg per day for 2 weeks, 300mg per day for 2 weeks, 450mg per day for 2 weeks, and a final dose, 600㎎ per day was continued. After achieve MR4.5, patients was received nilotinib consolidation therapy for 2 years. The primary end point was the proportion of patients who had treatment free remission at 12 months from the final day of the administration. The trough levels of NIL were examined and relapse was defined as a loss of MMR.
Results
Between November 2013 and August 2015, 26 patients was enrolled. 22 patients were previous treated and 4 patients were newly diagnosed. 16 patients were male and 10 patients were female. A median age was 55.2 years old (range 30-79). 21 patients were PS0, and 5 patients were PS 1. No patients were dropped out of stepwise Dose Escalation phase and consolidation phase. A total of 21 pts were found adverse events (81%), and 14 pts were found cutis such as itching and rash (54%). No severe adverse event was found and tolerability for NIL administration was 100%.No significant changes were found in the peripheral Lymphocytes count (CD3+, CD19+, and CD16+56+), but NK activities were significantly increased between before and after treatment by NIL (n=25, Before:6.184(%), After 9.48(%),. ⊿%：+53%, p-value 0.004).
Conclusion
The sustainable rate of the chemotherapy by NIL for CML-CP was 100% by the stepwise dose escalation method. These method may improve CML treatment. NK activities might be induced by NIL. Primary endpoint of this study,the proportion of patients who had treatment free remission at 12 months, would be presentated at EHA after day.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
Type: Publication Only
Background
The STIM trial, stood in innovative point of view, indicate that imatinib may be successfully stopped in patients with deep molecular responses. Subsequently, the feasibility of various TKIs discontinuation trials have been investigated. The most important factor in TKIs discontinuation trials is the molecular response of BCR-ABL. The molecular response affected by many factors, such as Sokal score, percentage of basophil, additional chromosome anomaly and so on. Another important factor for the success of TKIs stop study is adverse events of TKIs itself. Several patients are not able to continue the TKIs by the adverse events.
Aims
Stepwise dose escalation method of NIL improved the proportion of patients who had treatment free Remission or not. A prospective, multicenter, single-arm phase 2 trial was conducted.
Methods
The Stepwise Dose Escalation Method for Nilotinib Stop trial in Patients with Chronic Myeloid Leukemia (Step Stop trial) was a prospective, multicenter, single-arm phase 2 trial. Adult CML-CP patients with newly diagnosed or experienced TKIs (imatinib, dasatinib or nilotinib) was enrolled. The first half of this study was “stepwised induction (achieve CMR) and consolidation (for 2 years) phase”, stepwise dose escalation of NIL was conducted to avoid discontinuation of NIL by the adverse events. And the second half was “stop and monitoring phase”.Eligible patients were administered nilotinib with stepwise dose escalation method, i.e. 150mg per day for 2 weeks, 300mg per day for 2 weeks, 450mg per day for 2 weeks, and a final dose, 600㎎ per day was continued. After achieve MR4.5, patients was received nilotinib consolidation therapy for 2 years. The primary end point was the proportion of patients who had treatment free remission at 12 months from the final day of the administration. The trough levels of NIL were examined and relapse was defined as a loss of MMR.
Results
Between November 2013 and August 2015, 26 patients was enrolled. 22 patients were previous treated and 4 patients were newly diagnosed. 16 patients were male and 10 patients were female. A median age was 55.2 years old (range 30-79). 21 patients were PS0, and 5 patients were PS 1. No patients were dropped out of stepwise Dose Escalation phase and consolidation phase. A total of 21 pts were found adverse events (81%), and 14 pts were found cutis such as itching and rash (54%). No severe adverse event was found and tolerability for NIL administration was 100%.No significant changes were found in the peripheral Lymphocytes count (CD3+, CD19+, and CD16+56+), but NK activities were significantly increased between before and after treatment by NIL (n=25, Before:6.184(%), After 9.48(%),. ⊿%：+53%, p-value 0.004).
Conclusion
The sustainable rate of the chemotherapy by NIL for CML-CP was 100% by the stepwise dose escalation method. These method may improve CML treatment. NK activities might be induced by NIL. Primary endpoint of this study,the proportion of patients who had treatment free remission at 12 months, would be presentated at EHA after day.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
Abstract: PB1825
Type: Publication Only
Background
The STIM trial, stood in innovative point of view, indicate that imatinib may be successfully stopped in patients with deep molecular responses. Subsequently, the feasibility of various TKIs discontinuation trials have been investigated. The most important factor in TKIs discontinuation trials is the molecular response of BCR-ABL. The molecular response affected by many factors, such as Sokal score, percentage of basophil, additional chromosome anomaly and so on. Another important factor for the success of TKIs stop study is adverse events of TKIs itself. Several patients are not able to continue the TKIs by the adverse events.
Aims
Stepwise dose escalation method of NIL improved the proportion of patients who had treatment free Remission or not. A prospective, multicenter, single-arm phase 2 trial was conducted.
Methods
The Stepwise Dose Escalation Method for Nilotinib Stop trial in Patients with Chronic Myeloid Leukemia (Step Stop trial) was a prospective, multicenter, single-arm phase 2 trial. Adult CML-CP patients with newly diagnosed or experienced TKIs (imatinib, dasatinib or nilotinib) was enrolled. The first half of this study was “stepwised induction (achieve CMR) and consolidation (for 2 years) phase”, stepwise dose escalation of NIL was conducted to avoid discontinuation of NIL by the adverse events. And the second half was “stop and monitoring phase”.Eligible patients were administered nilotinib with stepwise dose escalation method, i.e. 150mg per day for 2 weeks, 300mg per day for 2 weeks, 450mg per day for 2 weeks, and a final dose, 600㎎ per day was continued. After achieve MR4.5, patients was received nilotinib consolidation therapy for 2 years. The primary end point was the proportion of patients who had treatment free remission at 12 months from the final day of the administration. The trough levels of NIL were examined and relapse was defined as a loss of MMR.
Results
Between November 2013 and August 2015, 26 patients was enrolled. 22 patients were previous treated and 4 patients were newly diagnosed. 16 patients were male and 10 patients were female. A median age was 55.2 years old (range 30-79). 21 patients were PS0, and 5 patients were PS 1. No patients were dropped out of stepwise Dose Escalation phase and consolidation phase. A total of 21 pts were found adverse events (81%), and 14 pts were found cutis such as itching and rash (54%). No severe adverse event was found and tolerability for NIL administration was 100%.No significant changes were found in the peripheral Lymphocytes count (CD3+, CD19+, and CD16+56+), but NK activities were significantly increased between before and after treatment by NIL (n=25, Before:6.184(%), After 9.48(%),. ⊿%：+53%, p-value 0.004).
Conclusion
The sustainable rate of the chemotherapy by NIL for CML-CP was 100% by the stepwise dose escalation method. These method may improve CML treatment. NK activities might be induced by NIL. Primary endpoint of this study,the proportion of patients who had treatment free remission at 12 months, would be presentated at EHA after day.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
Type: Publication Only
Background
The STIM trial, stood in innovative point of view, indicate that imatinib may be successfully stopped in patients with deep molecular responses. Subsequently, the feasibility of various TKIs discontinuation trials have been investigated. The most important factor in TKIs discontinuation trials is the molecular response of BCR-ABL. The molecular response affected by many factors, such as Sokal score, percentage of basophil, additional chromosome anomaly and so on. Another important factor for the success of TKIs stop study is adverse events of TKIs itself. Several patients are not able to continue the TKIs by the adverse events.
Aims
Stepwise dose escalation method of NIL improved the proportion of patients who had treatment free Remission or not. A prospective, multicenter, single-arm phase 2 trial was conducted.
Methods
The Stepwise Dose Escalation Method for Nilotinib Stop trial in Patients with Chronic Myeloid Leukemia (Step Stop trial) was a prospective, multicenter, single-arm phase 2 trial. Adult CML-CP patients with newly diagnosed or experienced TKIs (imatinib, dasatinib or nilotinib) was enrolled. The first half of this study was “stepwised induction (achieve CMR) and consolidation (for 2 years) phase”, stepwise dose escalation of NIL was conducted to avoid discontinuation of NIL by the adverse events. And the second half was “stop and monitoring phase”.Eligible patients were administered nilotinib with stepwise dose escalation method, i.e. 150mg per day for 2 weeks, 300mg per day for 2 weeks, 450mg per day for 2 weeks, and a final dose, 600㎎ per day was continued. After achieve MR4.5, patients was received nilotinib consolidation therapy for 2 years. The primary end point was the proportion of patients who had treatment free remission at 12 months from the final day of the administration. The trough levels of NIL were examined and relapse was defined as a loss of MMR.
Results
Between November 2013 and August 2015, 26 patients was enrolled. 22 patients were previous treated and 4 patients were newly diagnosed. 16 patients were male and 10 patients were female. A median age was 55.2 years old (range 30-79). 21 patients were PS0, and 5 patients were PS 1. No patients were dropped out of stepwise Dose Escalation phase and consolidation phase. A total of 21 pts were found adverse events (81%), and 14 pts were found cutis such as itching and rash (54%). No severe adverse event was found and tolerability for NIL administration was 100%.No significant changes were found in the peripheral Lymphocytes count (CD3+, CD19+, and CD16+56+), but NK activities were significantly increased between before and after treatment by NIL (n=25, Before:6.184(%), After 9.48(%),. ⊿%：+53%, p-value 0.004).
Conclusion
The sustainable rate of the chemotherapy by NIL for CML-CP was 100% by the stepwise dose escalation method. These method may improve CML treatment. NK activities might be induced by NIL. Primary endpoint of this study,the proportion of patients who had treatment free remission at 12 months, would be presentated at EHA after day.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
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