Trial Outcomes & Findings for Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukaemia (CML) in Chronic Phase Who Are Intolerant to Prior Tyrosine Kinase Inhibitors. (NCT NCT02108951)
NCT ID: NCT02108951
Last Updated: 2017-10-27
Results Overview
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
TERMINATED
PHASE3
20 participants
Baseline, 96 weeks (24 months)
2017-10-27
Participant Flow
Participant milestones
| Measure |
Nilotinib
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Overall Study
STARTED
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20
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Overall Study
COMPLETED
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4
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Overall Study
NOT COMPLETED
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16
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Reasons for withdrawal
| Measure |
Nilotinib
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Overall Study
Lost to Follow-up
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1
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Overall Study
Patient's/guardian's decision
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1
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Overall Study
Study Terminated by Sponsor
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14
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Baseline Characteristics
Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukaemia (CML) in Chronic Phase Who Are Intolerant to Prior Tyrosine Kinase Inhibitors.
Baseline characteristics by cohort
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Age, Continuous
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53.9 years
STANDARD_DEVIATION 15.1 • n=5 Participants
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Sex: Female, Male
Female
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14 Participants
n=5 Participants
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Sex: Female, Male
Male
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6 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline, 96 weeks (24 months)Population: The full analysis set (FAS) consists of all patients enrolled into the study.
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
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50 Percentage of participants
Interval 27.2 to 72.8
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PRIMARY outcome
Timeframe: Baseline, 48 weeks (12 months), 96 weeks (24 months)Population: The full analysis set (FAS) consists of all patients enrolled into the study. Analysis of MR4.0 was undertaken on the subgroup of the FAS that was not at MR4.0 at baseline.
Molecular Response (MR4.0) rate is defined as the percentage of patients who have achieved a 4-log reduction in BCR-ABL levels at 12 months and 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patients were classified as achieving a 1 log reduction in BCR-ABL.
Outcome measures
| Measure |
Nilotinib
n=17 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
Within 12 months
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65 Percentage of participants
Interval 38.3 to 85.8
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Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
Within 24 months
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71 Percentage of participants
Interval 44.0 to 89.7
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PRIMARY outcome
Timeframe: Baseline, 48 weeks (12 months), 96 weeks (24 months)Population: The full analysis set (FAS) consists of all patients enrolled into the study.Analysis of MMR was undertaken on the subgroup of the FAS that was not at MMR at baseline.
Major Molecular Response (MMR) rate is defined as the percentage of patients who have achieved a 3 log reduction in BCR-ABL levels at 12 months and at 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood at the 12 and 24 months following the commencement of nilotinib therapy. MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 \* the baseline Value, the patient will be classified as achieving a 1 log drop.
Outcome measures
| Measure |
Nilotinib
n=8 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
Within 12 months
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75 Percentage of participants
Interval 34.9 to 96.8
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Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
Within 24 months
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75 Percentage of participants
Interval 34.9 to 96.8
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PRIMARY outcome
Timeframe: Baseline, 96 weeks (24 months)Population: The full analysis set (FAS) consists of all patients enrolled into the study.
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. Deep molecular response (MR4.5) rate was defined as the percentage of patients who have achieved a 4.5-log reduction (MR4.5) in BCR-ABL levels during the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
Achieved MR4.5
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56.1 months
Standard Deviation 42.06
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Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
Did not achieve MR4.5
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45.9 months
Standard Deviation 47.81
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PRIMARY outcome
Timeframe: Baseline, 96 weeks (24 months)Population: The full analysis set (FAS) consists of all patients enrolled into the study. 'n' in categories indicates patients achieved or did not achieve MR4.5 during 24 months
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 achieved (n=10): No response at baseline
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3 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 achieved : MMR at baseline
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4 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 achieved : MR4.0 at baseline
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1 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 achieved: MR4.5 at baseline
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2 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 not achieved: No response at baseline
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5 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 not achieved: MMR at baseline
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5 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 not achieved: MR4.0 at baseline
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0 Participants
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Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
MR4.5 not achieved: MR4.5 at baseline
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0 Participants
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SECONDARY outcome
Timeframe: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96Population: Full analysis set. n = number of patients with evaluable data at the defined time point
No response corresponds to a BCR-ABL ratio \< 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Baseline : No Response
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40.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 4: No response
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33.3 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 8: No response
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26.3 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 12: No response
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15.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 24: No response
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18.8 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 36: No response
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6.7 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 48: No response
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7.1 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 60: No response
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0.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 72: No response
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0.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 84: No response
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0.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 96/End of study: No response
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5.6 percentage of patients
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SECONDARY outcome
Timeframe: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96Population: Full analysis set. n = number of patients with evaluable data at the defined time point
MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Baseline : MMR
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45.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 4: MMR
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55.6 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 8: MMR
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36.8 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 12: MMR
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40.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 24: MMR
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31.3 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 36: MMR
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26.7 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 48: MMR
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28.6 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 60: MMR
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12.5 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 72: MMR
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0.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 84: MMR
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0.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 96/End of study: MMR
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33.3 percentage of patients
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SECONDARY outcome
Timeframe: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96Population: Full analysis set
MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Baseline : MR4.0
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5.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 4: MR4.0
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5.6 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 8: MR4.0
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15.8 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 12: MR4.0
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10.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 24: MR4.0
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18.8 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 36: MR4.0
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20.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 48: MR4.0
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14.3 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 60: MR4.0
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12.5 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 72: MR4.0
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60.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 84: MR4.0
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33.3 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 96/End of study: MR4.0
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16.7 percentage of patients
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SECONDARY outcome
Timeframe: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96Population: Full analysis set. n = number of patients with evaluable data at the defined time point
MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Baseline : MR4.5
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10.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 4: MR4.5
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5.6 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 8: MR4.5
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21.1 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 12: MR4.5
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35.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 24: MR4.5
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31.3 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 36: MR4.5
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46.7 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 48: MR4.5
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50.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 60: MR4.5
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75.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 72: MR4.5
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40.0 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 84: MR4.5
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66.7 percentage of patients
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Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
Week 96/End of study: MR4.5
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44.4 percentage of patients
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SECONDARY outcome
Timeframe: 96 weeks (24 months)Population: The full analysis set (FAS) consists of all patients enrolled into the study. N represents all patients in FAS who achieved MR4.5.
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels is measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. The derivation of time to molecular response for patients in the study was measured from the date of first nilotinib use, defined as follows: Days to MR4.5 = date of assessment where BCR-ABL ratio is 0.0032% IS - date of baseline + 1.
Outcome measures
| Measure |
Nilotinib
n=10 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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|---|---|
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Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)
|
343 days
Interval 64.0 to
Upper limit is not estimable due to the low number of patients achieving MR4.5.
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SECONDARY outcome
Timeframe: 96 weeks (24 months)Population: The FAS consists of all patients enrolled into the study. There were no withdrawals due to progression to BC or AP disease, and there were no recorded deaths during the study.
PFS was defined as the time from the date of baseline visit to the date of earliest progression-defining event: namely progression (or withdrawal due to progression to blast crisis (BC) or accelerated phase (AP) disease), or death from any cause. Patients who did not progress were censored at earliest of the following: * the date of the 24-month visit; * the date of loss to follow-up; * the date of discontinuation of study treatment for any reason other than progression to BC, or AP disease, or death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 96 weeks (24 months)Population: There were no patients in the study who were recorded as experiencing treatment failure.
EFS was defined as the time from date of baseline visit to the first occurrence of any of the following: Disease progression, treatment failure or death from any cause, whichever was earlier. Patients who did not have an event of interest were censored at earliest of the following: * the date of the 24-month visit; * the date of loss to follow-up; * the date of withdrawal from the study for any reason other than lack of efficacy/progressive disease, tolerance to reduced dose or death
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, week 12 (month 3)Population: The Safety Set (SS) consisted of all patients in the FAS who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
The total number of patients that have showed improvement with respect to CTCAE grades at the time of the 12-week visit are reported. Improved is defined as prior to, or at the time of the 12-week visit, the AE has completely resolved.
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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|---|---|
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Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
Improved: No
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9 Participants
|
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Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
Improved : Yes
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline, week 12, 24, 48, 96Population: The full analysis set (FAS) consists of all patients enrolled into the study. 'n' in the categories represents the number of patients with evaluable data for MDASI part 1/MDASI part 2/CML component at different time points. Week 96 includes end of study results for patients that did not complete the study.
Quality of life was assessed using the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) self-administered questionnaire for adult CML patients. The questionnaire consisted of 13 core questions in part I measuring the severity of symptoms, 6 questions in part 2 assessing the interference of symptoms on daily living. The CML component of the MDASI provided an additional 7 CML-specific symptom items: diarrhea, swelling, rash/skin change, muscle soreness/cramping, bruising/bleeding easily, malaise, and headache. In part I (13 questions) and the CML component (7 questions) each question was scored from 0 to 10 where 0 indicates a symptom is not present and 10 indicate the symptom is "as bad as you can imagine". For part 1 the total score can therefore range from 0 to 130 and for CML 0 to 70. Part 2 is also recorded on a 0 to 10 scale, but 0 now indicates that the symptom "did not interfere" and 10 "interfered completely". The total score can range from 0 to 60.
Outcome measures
| Measure |
Nilotinib
n=20 Participants
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study.
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|---|---|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Baseline: MDASI part 1
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26.6 units on a scale
Standard Deviation 23.88
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 12: MDASI part 1
|
22.7 units on a scale
Standard Deviation 20.31
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 24: MDASI part 1
|
20.7 units on a scale
Standard Deviation 18.08
|
|
Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 48: MDASI part 1
|
20.4 units on a scale
Standard Deviation 16.57
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 96: MDASI part 1
|
17.5 units on a scale
Standard Deviation 20.44
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Baseline: MDASI part 2
|
12.4 units on a scale
Standard Deviation 14.17
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 12: MDASI part 2
|
7.8 units on a scale
Standard Deviation 11.92
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 24: MDASI part 2
|
8.2 units on a scale
Standard Deviation 12.20
|
|
Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 48: MDASI part 2
|
7.6 units on a scale
Standard Deviation 10.53
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 96: MDASI part 2
|
9.9 units on a scale
Standard Deviation 15.59
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Baseline: CMLcomponent
|
40.9 units on a scale
Standard Deviation 35.02
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 12: CMLcomponent
|
31.5 units on a scale
Standard Deviation 30.10
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 24: CMLcomponent
|
30.8 units on a scale
Standard Deviation 28.62
|
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 48: CMLcomponent
|
28.2 units on a scale
Standard Deviation 24.43
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Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Week 96 CMLcomponent
|
25.4 units on a scale
Standard Deviation 31.06
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Adverse Events
Nilotinib
Serious adverse events
| Measure |
Nilotinib
n=20 participants at risk
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study
|
|---|---|
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Infections and infestations
Pneumonia
|
5.0%
1/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
Other adverse events
| Measure |
Nilotinib
n=20 participants at risk
Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study
|
|---|---|
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Gastrointestinal disorders
Constipation
|
20.0%
4/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
20.0%
4/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
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General disorders
Fatigue
|
55.0%
11/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
General disorders
Influenza like illness
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Infections and infestations
Lower respiratory tract infection
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
4/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Infections and infestations
Urinary tract infection
|
15.0%
3/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
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Investigations
Alanine aminotransferase increased
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Investigations
Blood alkaline phosphatase increased
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Investigations
Blood bilirubin increased
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Investigations
Gamma-glutamyltransferase increased
|
20.0%
4/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
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Investigations
Weight decreased
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.0%
3/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
20.0%
4/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
20.0%
4/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
2/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.0%
3/20 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER