CML
Conditions
Keywords
CML, chronic myeloid leukemia, stop, niotinib, discontinue, imatinib, switch, MR4.5, undetectable, bcr-abl
Brief summary
To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5
Detailed description
Study protocol included criteria for study termination that was met when \> 2 patients lost CCyR during TFR phase (\> 1% BCR-ABL); This study was terminated early as \> 2 cases of confirmed loss of complete cytogenetic response were reported despite BCR-ABL monitoring during the TFR Phase. All cases achieved MR4.5 after Nilotinib treatment re-initiation and maintained until end of study; trial did not mandate re-initiation within 4 weeks after loss of MMR\_ that was a requirement in other Nilotinib TFR trials Initial sample size was 300 patients with CML-CP; Amendment #2 in June 2015 reduced sample size to 59 due to recruitment challenges; Study endpoint analysis and interpretations of data were challenging due to small sample size for early study closure..
Interventions
DRUGnilotinib
Nilotinib will be provided as 150 mg capsules. Patients will take nilotinib 300mg twice daily on study and dose modifications to 450mg once daily is permitted per protocol.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* diagnosis of CML * Treated with at least 1 year of imatinib * Bcr-Abl level by PCR must be less than or equal to 0.1% and greater than 0.0032% by PCR reported on the International scale confirmed during screening * Written informed consent obtained prior to any screening procedures performed
Exclusion criteria
* T315I mutation * Prior imatinib failure or had accelerated phase or blast crisis CML * Impaired cardiac function * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase | 6 months after stopping nilotinib therapy | Percentage of particpants without confirmed loss of MMR within 6 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, in the first 6 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase. Molecular relapse is defined as having a confirmed BCR-ABL ratio above MMR (2 consecutive BCR-ABL levels \>0.1% IS taken approximately 4 weeks apart). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5). | 7 years | Relapse-free survival after the start of the TFR phase was summarized using the product-limit (Kaplan-Meier) estimates. The median for the relapse free survival and its 95% confidence intervals were provided. This analysis was performed on the FAS. Patients who dropped out without relapse were treated as censored observations. |
| Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase | 12 and 24 months after starting the TFR | The percentage of participants without confirmed loss of MRR at 12 and 24 months is calculated by dividing the number of patients with no documented confirmed loss of MR4 at 12 and 24 months after starting the nilotinib TFR phase by the number of patients who entered nilotinib TFR phase. |
| Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse | Restart of nilotinib up to month 6, 12 and 24 | The percentage of participants who regained MR4.5 after restarting nilotinib will be calculated as the number of patients who achieved MR4.5 after having lost MR4 divided by the number of patients who lost MR4. |
| Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause. | Baseline up to approximately 5 years | Progression to AP/BC and death where the failure event is the earliest occurrence of the following event: progression to AP/BC date. |
| Overall Survival (OS) | Baseline up to approximately 5 years | OS was defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause. |
| Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | From baseline to time to when MR4.5 is confirmed, up to 24 months, and from end of Consolidation Phase to 6 and 12 months into the TFR Phase | The M.D. Anderson Symptom Inventory for CML patients (MDASI-CML) was used to assess the nature and impact of symptom burden on life. It consisted of 20 validated symptom items and 6 validated interference items. Each item was assessed on an 11 point scale with responses from 0-10, 0=not present and 10=as bad as you can imagine. Symptom score (SS) was calculated when a patient scored at least 8 items of the symptom items using the formula: (sum of scores for the items answered) / number of items answered. If a subject responded to \< 8 symptom items, the score was considered missing. Interference score (IS) was calculated when a patient scored at least 4 items using the formula: (sum of scores for the items answered)/number of items answered. If a subject responded to \< 4 interference items, the score was considered missing. The total symptom score was 0-200 and total interference score was 0-60. Mean change from baseline was summarized at all post-baseline time points |
| Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | From baseline to time to when MR4.5, up to 24 months, is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase | The EQ-5D-3L questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and visual analog has a scale 0 to 100 (0=worst imaginable health state, 100=best imaginable health state). |
| Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase | The SF-8 questionnaire consisted of 8 items (general health, physical functioning, role physical, bodily pain, vitality, social functioning, role-emotional and mental health) and was used to assess the impact of nilotinib treatment discontinuation on the quality of life. Each item had a 1 to 5 or 1 to 6 point response range and the higher number in the raw scores indicated poorer quality of life. The physical and mental component summary measures were calculated using a norm-based scoring method given in the instrument guidelines. These norm-based scores were summarized at baseline and mean change from baseline for post-baseline time points. The norm-based scores (based on the US population) had a mean of 50 and standard deviation of 10. Higher norm-based summary scores indicated better health |
| Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | At month 3 in Consolidation Phase | The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point |
| Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Month 12 in Consolidation Phase | The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point |
| Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Month 24 in Consolidation Phase | The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point |
| Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Month 6 in in Treatment Free Remission Phase | The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point |
| Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Month 12 in in Treatment Free Remission Phase | The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Patients entered a monitoring phase for 2 years and received 300 mg nilotinib mg bid. Patients who achieved MR4.5 entered a Consolidation Phase and were treated with nilotinib for 2 years. If MR4.5 was sustained during the Consolidation phase, patients were eligible to stop taking niltoinib during the treatment-free remission (TFR) phase. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Consolidation Phase | Administrative problems | 9 |
| Consolidation Phase | Adverse Event | 2 |
| Consolidation Phase | Unsatisfactory therapeutic effect | 4 |
| Consolidation Phase | Withdrawal by Subject | 4 |
| Monitoring Phase | Abnormal laboratory value(s) | 1 |
| Monitoring Phase | Adverse Event | 4 |
| Monitoring Phase | Did not achieve MR4.5 | 1 |
| Monitoring Phase | Unsatisfactory therapeutic effect | 7 |
| Monitoring Phase | Withdrawal by Subject | 5 |
| Re-initiation Phase | Administrative problems | 10 |
| Re-initiation Phase | Adverse Event | 1 |
| Re-initiation Phase | No longer required treatment | 1 |
| Re-initiation Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 55.5 years STANDARD_DEVIATION 12.44 |
| Race/Ethnicity, Customized Black | 2 participants |
| Race/Ethnicity, Customized Caucasian | 25 participants |
| Race/Ethnicity, Customized Other | 5 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 59 |
| other Total, other adverse events | 59 / 59 |
| serious Total, serious adverse events | 19 / 59 |
Outcome results
Primary
Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase
Percentage of particpants without confirmed loss of MMR within 6 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, in the first 6 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase. Molecular relapse is defined as having a confirmed BCR-ABL ratio above MMR (2 consecutive BCR-ABL levels \>0.1% IS taken approximately 4 weeks apart).
Time frame: 6 months after stopping nilotinib therapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Free Remission | Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase | Number of participants | 12 Participants |
Secondary
Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set
The EQ-5D-3L questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and visual analog has a scale 0 to 100 (0=worst imaginable health state, 100=best imaginable health state).
Time frame: From baseline to time to when MR4.5, up to 24 months, is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase
Population: Number of participants who completed questionnaire varied across visits
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | Baseline (observed value) | 83.250 scores on scale |
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | Consolidation Ph - M 3 (change from BL) | 2.000 scores on scale |
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | Consolidation Ph - M 12 (change from BL) | 3.250 scores on scale |
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | Consolidation Ph - M 24 (change from BL) | 1.350 scores on scale |
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | TFR Baseline (observed value) | 80.00 scores on scale |
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | TFR - Month 6 (change from BL) | 10.00 scores on scale |
| Treatment Free Remission | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set | TFR - Month 12 (change from BL) | 0.000 scores on scale |
Secondary
Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set
The SF-8 questionnaire consisted of 8 items (general health, physical functioning, role physical, bodily pain, vitality, social functioning, role-emotional and mental health) and was used to assess the impact of nilotinib treatment discontinuation on the quality of life. Each item had a 1 to 5 or 1 to 6 point response range and the higher number in the raw scores indicated poorer quality of life. The physical and mental component summary measures were calculated using a norm-based scoring method given in the instrument guidelines. These norm-based scores were summarized at baseline and mean change from baseline for post-baseline time points. The norm-based scores (based on the US population) had a mean of 50 and standard deviation of 10. Higher norm-based summary scores indicated better health
Time frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase
Population: Number of participants who completed questionnaire varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | Baseline | 50.508 scores on a scale | Standard Deviation 8.4313 |
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | Consolidation Ph - M 3 | 50.720 scores on a scale | Standard Deviation 7.6047 |
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | Consolidation Ph - M 12 | 49.020 scores on a scale | Standard Deviation 10.1851 |
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | Consolidation Ph - M 24 | 47.648 scores on a scale | Standard Deviation 8.7416 |
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | TFR Baseline | 48.382 scores on a scale | Standard Deviation 8.6503 |
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | TFR - Month 6 | 46.605 scores on a scale | Standard Deviation 9.5042 |
| Treatment Free Remission | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set | TFR - Month 12 | 46.006 scores on a scale | Standard Deviation 8.6997 |
Secondary
Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment
The M.D. Anderson Symptom Inventory for CML patients (MDASI-CML) was used to assess the nature and impact of symptom burden on life. It consisted of 20 validated symptom items and 6 validated interference items. Each item was assessed on an 11 point scale with responses from 0-10, 0=not present and 10=as bad as you can imagine. Symptom score (SS) was calculated when a patient scored at least 8 items of the symptom items using the formula: (sum of scores for the items answered) / number of items answered. If a subject responded to \< 8 symptom items, the score was considered missing. Interference score (IS) was calculated when a patient scored at least 4 items using the formula: (sum of scores for the items answered)/number of items answered. If a subject responded to \< 4 interference items, the score was considered missing. The total symptom score was 0-200 and total interference score was 0-60. Mean change from baseline was summarized at all post-baseline time points
Time frame: From baseline to time to when MR4.5 is confirmed, up to 24 months, and from end of Consolidation Phase to 6 and 12 months into the TFR Phase
Population: Number of participants who completed questionnaire varied across visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS Consolidation Ph - M 24 (change from BL) n=26 | 0.026 scores on a scale | Standard Deviation 0.1402 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS TFR Baseline (observed value) n=32 | 0.160 scores on a scale | Standard Deviation 0.1496 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS TFR - Month 6 (change from BL) n=10 | -0.005 scores on a scale | Standard Deviation 0.1773 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS TFR - Month 12 (change from BL) n=5 | -0.032 scores on a scale | Standard Deviation 0.1034 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS Baseline (observed value), n=40 | 0.125 scores on a scale | Standard Deviation 0.1314 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS Consolidation Ph - M 3 (change from BL) n=26 | 0.012 scores on a scale | Standard Deviation 0.1362 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | SS Consolidation Ph - M 12 (change from BL) n=30 | 0.021 scores on a scale | Standard Deviation 0.114 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS Baseline (observed value), n=40 | 0.123 scores on a scale | Standard Deviation 0.2156 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS Consolidation Ph - M 3 (change from BL) n=25 | 0.008 scores on a scale | Standard Deviation 0.1911 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS Consolidation Ph - M 12 (change from BL) n=30 | -0.005 scores on a scale | Standard Deviation 0.1983 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS Consolidation Ph - M 24 (change from BL) n=26 | 0.015 scores on a scale | Standard Deviation 0.1942 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS TFR Baseline (observed value) n=32 | 0.141 scores on a scale | Standard Deviation 0.2067 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS TFR - Month 6 (change from BL) n=10 | -0.015 scores on a scale | Standard Deviation 0.178 |
| Treatment Free Remission | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment | IS TFR - Month 12 (change from BL) n=5 | -0.037 scores on a scale | Standard Deviation 0.188 |
Secondary
Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause.
Progression to AP/BC and death where the failure event is the earliest occurrence of the following event: progression to AP/BC date.
Time frame: Baseline up to approximately 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Free Remission | Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause. | 0 participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.
Time frame: Baseline up to approximately 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Free Remission | Overall Survival (OS) | 0 participants |
Secondary
Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set
The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point
Time frame: Month 12 in Consolidation Phase
Population: all completers did not complete all categories of questionaire
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 18 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 23 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Mobility | Number of participants | 23 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 31 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 21 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 7 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Mobility | Number of participants | 8 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 11 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 10 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 1 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Mobility | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 1 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
Secondary
Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set
The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point
Time frame: Month 12 in in Treatment Free Remission Phase
Population: all completers did not complete all categories of questionaire
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Pain/Discomfort | Number of participants | 1 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Usual Activities | Number of participants | 4 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Mobility | Number of participants | 4 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Self-Care | Number of participants | 5 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Anxiety / Depresssion | Number of participants | 3 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Usual Activities | Number of participants | 1 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Mobility | Number of participants | 1 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Pain/Discomfort | Number of participants | 4 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Anxiety / Depresssion | Number of participants | 2 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Anxiety / Depresssion | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Pain/Discomfort | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Mobility | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Usual Activities | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
Secondary
Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set
The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point
Time frame: Month 24 in Consolidation Phase
Population: all completers did not complete all categories of questionaire
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 17 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 23 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Mobility | Number of participants | 19 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 28 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 19 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 4 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Mobility | Number of participants | 8 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 9 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 8 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 2 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Mobility | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
Secondary
Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set
The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point
Time frame: At month 3 in Consolidation Phase
Population: all completers did not complete all categories of questionaire
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 12 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 21 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Mobility | Number of participants | 22 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 25 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 20 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 5 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Mobility | Number of participants | 4 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 1 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 13 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 6 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Anxiety / Depresssion | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Pain/Discomfort | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Mobility | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Usual Activities | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
Secondary
Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set
The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point
Time frame: Month 6 in in Treatment Free Remission Phase
Population: all completers did not complete all categories of questionaire
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Pain/Discomfort | Number of participants | 5 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Usual Activities | Number of participants | 10 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Mobility | Number of participants | 7 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Self-Care | Number of participants | 10 Participants |
| Treatment Free Remission | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Anxiety / Depresssion | Number of participants | 8 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Usual Activities | Number of participants | 0 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Mobility | Number of participants | 3 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Pain/Discomfort | Number of participants | 4 Participants |
| Some Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Anxiety / Depresssion | Number of participants | 2 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Anxiety / Depresssion | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Pain/Discomfort | Number of participants | 1 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Mobility | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Usual Activities | Number of participants | 0 Participants |
| Extreme Problems | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set | Self-Care | Number of participants | 0 Participants |
Secondary
Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse
The percentage of participants who regained MR4.5 after restarting nilotinib will be calculated as the number of patients who achieved MR4.5 after having lost MR4 divided by the number of patients who lost MR4.
Time frame: Restart of nilotinib up to month 6, 12 and 24
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse | Month 12 | Number of participants | 17 Participants |
| Treatment Free Remission | Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse | Month 24 | Number of participants | 17 Participants |
| Treatment Free Remission | Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse | Month 6 | Number of participants | 7 Participants |
Secondary
Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase
The percentage of participants without confirmed loss of MRR at 12 and 24 months is calculated by dividing the number of patients with no documented confirmed loss of MR4 at 12 and 24 months after starting the nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.
Time frame: 12 and 24 months after starting the TFR
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment Free Remission | Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase | Month 12 | Number of participants | 8 Participants |
| Treatment Free Remission | Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase | Month 24 | Number of participants | 2 Participants |
Secondary
Relapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5).
Relapse-free survival after the start of the TFR phase was summarized using the product-limit (Kaplan-Meier) estimates. The median for the relapse free survival and its 95% confidence intervals were provided. This analysis was performed on the FAS. Patients who dropped out without relapse were treated as censored observations.
Time frame: 7 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment Free Remission | Relapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5). | 21.4 weeks |