ENESTgoal: A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation
Study Details
Study Description
Brief Summary
To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
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..
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment Free Remission 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. |
Drug: nilotinib
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Alabama Comprehensive Cancer Center University of Alabama (8) | Birmingham | Alabama | United States | 35294 |
2 | Banner MD Anderson Cancer Center Banner MD Anderson (2) | Gilbert | Arizona | United States | 85234 |
3 | Scottsdale Healthcare/TGen Clinical Research Service SC | Scottsdale | Arizona | United States | 85258 |
4 | Highlands Oncology Group | Fayetteville | Arkansas | United States | 72703 |
5 | City of Hope National Medical Center Dept of Oncology | Duarte | California | United States | 91010 3000 |
6 | Compassionate Care Research Group Inc CCCMG | Fountain Valley | California | United States | 92708 |
7 | UC San Diego UC San Diego Cancer Ctr | La Jolla | California | United States | 92093-0987 |
8 | Wilshire Oncology Medical Group Corona Cancer Center | Multiple Locations | California | United States | |
9 | Epic-Care | Pleasant Hill | California | United States | 94523 |
10 | Sutter Institute for Medical Research Oncology/Hematology | Sacramento | California | United States | 95816-5199 |
11 | St Joseph Heritage Healthcare | Santa Rosa | California | United States | 94503 |
12 | Rocky Mountain Cancer Centers USOR | Boulder | Colorado | United States | 80304 |
13 | Florida Cancer Specialists DeptofFloridaCancerSpecialists | Fort Myers | Florida | United States | 33901 |
14 | MD Anderson Cancer Center - Orlando Cancer Center | Orlando | Florida | United States | 32806 |
15 | H Lee Moffitt Cancer Center and Research Institute H. Lee Moffitt Cancer Ctr (67) | Tampa | Florida | United States | 33612 |
16 | Stroger Cook County Hospital Division of Hematology & Onc | Chicago | Illinois | United States | 60612 |
17 | University of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
18 | University of Iowa Hospitals and Clinics Holden Comprehensive Cancer Ct | Iowa City | Iowa | United States | 52242 |
19 | University of Kansas Hospital and Medical Center Clinical Research Center | Kansas City | Kansas | United States | 66160 |
20 | Cancer Center of Kansas | Wichita | Kansas | United States | 67214-3728 |
21 | Christus Schumpert Health System | Shreveport | Louisiana | United States | 71101 |
22 | Michigan State University / Breslin Cancer Center Breslin Cancer Center (3) | Lansing | Michigan | United States | |
23 | Billings Clinic Billings Clinic (8) | Billings Montana | Montana | United States | 59101 |
24 | Hackensack University Medical Center John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
25 | Hematology Oncology Associates of Northern New Jersey PA Dept of Hem-Onc of Northern NJ | Morristown | New Jersey | United States | 07962 |
26 | Montefiore Medical Center Montefiore Medicial Center | Bronx | New York | United States | 10467 |
27 | Memorial Sloan Kettering Memorial Sloan Kettering (63) | New York | New York | United States | 10017 |
28 | Weill Cornell Medical Center Dept. of Oncology | New York | New York | United States | 10021 |
29 | Columbia University Medical Center Herbert Irving Pavilion | New York | New York | United States | 10032 |
30 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
31 | Westchester Medical Center NY Medical College | Valhalla | New York | United States | 10595 |
32 | Duke University Medical Center Duke University Med Ctr | Durham | North Carolina | United States | 27710 |
33 | Carolina Oncology Specialists, PC | Hickory | North Carolina | United States | 28602 |
34 | Wake Forest University Health Sciences Hematology and Oncology | Winston-Salem | North Carolina | United States | 27157 |
35 | Ohio State Comprehensive Cancer Center/James Cancer Hospital OSU Medical Center | Columbus | Ohio | United States | 43210 |
36 | Northwest Cancer Specialists Compass Oncology -BKM | Portland | Oregon | United States | 97210 |
37 | University of South Carolina-Hollings Cancer Center Medical University of SC | Columbia | South Carolina | United States | 29203 |
38 | Tennessee Oncology Dept. of Centennial Medical | Nashville | Tennessee | United States | 37203 |
39 | Vanderbilt Univeristy Ingram Cancer Center (10) | Nashville | Tennessee | United States | 37232 |
40 | Hendrick Cancer Center Hendricks Cancer Center | Abilene | Texas | United States | 79601 |
41 | Texas Oncology Texas Oncology - McAllen | Dallas | Texas | United States | 75246 |
42 | Texas Oncology Texas Oncology - Plano West | Dallas | Texas | United States | 75246 |
43 | Texas Oncology P A Texas Oncology - Midland | Dallas | Texas | United States | 75251 |
44 | University of Texas Medical Branch SC | Galveston | Texas | United States | 77555-1188 |
45 | Oncology Consultants Oncology Consultants, P.A. | Houston | Texas | United States | 77024 |
46 | The Methodist Hospital Cornell University | Houston | Texas | United States | 77030 |
47 | South Texas Cancer Center- McAllen | McAllen | Texas | United States | 78503 |
48 | Brooke Army Medical Center Brooke Army Medical | San Antonio | Texas | United States | 78234 |
49 | Waco Cancer and Research Center | Waco | Texas | United States | 76712 |
50 | University of Utah / Huntsman Cancer Institute Huntsman Cancer Center | Salt Lake City | Utah | United States | 84103 |
51 | University of Virginia | Charlottesville | Virginia | United States | 22908 |
52 | Kadlec Clinic Hematology and Oncology SC | Kennewick | Washington | United States | 99336 |
53 | West Virginia University/ Mary Babb Randolph Cancer Center Mary Babb Randolph Cancer Ctr | Morgantown | West Virginia | United States | 26506 |
54 | Medical College of Wisconsin Med College of WI | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.- CAMN107AUS37
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | All patients enrolled in trial |
Period Title: Monitoring Phase | |
STARTED | 59 |
COMPLETED | 41 |
NOT COMPLETED | 18 |
Period Title: Monitoring Phase | |
STARTED | 41 |
COMPLETED | 22 |
NOT COMPLETED | 19 |
Period Title: Monitoring Phase | |
STARTED | 32 |
COMPLETED | 32 |
NOT COMPLETED | 0 |
Period Title: Monitoring Phase | |
STARTED | 17 |
COMPLETED | 4 |
NOT COMPLETED | 13 |
Baseline Characteristics
Arm/Group Title | Overall |
---|---|
Arm/Group Description | 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. |
Overall Participants | 32 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
55.5
(12.44)
|
Sex: Female, Male (Count of Participants) | |
Female |
13
40.6%
|
Male |
19
59.4%
|
Race/Ethnicity, Customized (participants) [Number] | |
Caucasian |
25
78.1%
|
Black |
2
6.3%
|
Other |
5
15.6%
|
Outcome Measures
Title | Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 32 |
Number of participants |
12
37.5%
|
Title | 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). |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 32 |
Median (95% Confidence Interval) [weeks] |
21.4
|
Title | Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 32 |
Number of participants |
8
25%
|
Number of participants |
2
6.3%
|
Title | Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 17 |
Number of participants |
7
21.9%
|
Number of participants |
17
53.1%
|
Number of participants |
17
53.1%
|
Title | Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause. |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 32 |
Number [participants] |
0
0%
|
Title | Overall Survival (OS) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 32 |
Number [participants] |
0
0%
|
Title | Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Number of participants who completed questionnaire varied across visits |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 59 |
SS Baseline (observed value), n=40 |
0.125
(0.1314)
|
SS Consolidation Ph - M 3 (change from BL) n=26 |
0.012
(0.1362)
|
SS Consolidation Ph - M 12 (change from BL) n=30 |
0.021
(0.1140)
|
SS Consolidation Ph - M 24 (change from BL) n=26 |
0.026
(0.1402)
|
SS TFR Baseline (observed value) n=32 |
0.160
(0.1496)
|
SS TFR - Month 6 (change from BL) n=10 |
-0.005
(0.1773)
|
SS TFR - Month 12 (change from BL) n=5 |
-0.032
(0.1034)
|
IS Baseline (observed value), n=40 |
0.123
(0.2156)
|
IS Consolidation Ph - M 3 (change from BL) n=25 |
0.008
(0.1911)
|
IS Consolidation Ph - M 12 (change from BL) n=30 |
-0.005
(0.1983)
|
IS Consolidation Ph - M 24 (change from BL) n=26 |
0.015
(0.1942)
|
IS TFR Baseline (observed value) n=32 |
0.141
(0.2067)
|
IS TFR - Month 6 (change from BL) n=10 |
-0.015
(0.1780)
|
IS TFR - Month 12 (change from BL) n=5 |
-0.037
(0.1880)
|
Title | Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Number of participants who completed questionnaire varied across visits |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 36 |
Baseline (observed value) |
83.250
|
Consolidation Ph - M 3 (change from BL) |
2.000
|
Consolidation Ph - M 12 (change from BL) |
3.250
|
Consolidation Ph - M 24 (change from BL) |
1.350
|
TFR Baseline (observed value) |
80.00
|
TFR - Month 6 (change from BL) |
10.00
|
TFR - Month 12 (change from BL) |
0.000
|
Title | Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Number of participants who completed questionnaire varied across visits |
Arm/Group Title | Treatment Free Remission |
---|---|
Arm/Group Description | 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. |
Measure Participants | 41 |
Baseline |
50.508
(8.4313)
|
Consolidation Ph - M 3 |
50.720
(7.6047)
|
Consolidation Ph - M 12 |
49.020
(10.1851)
|
Consolidation Ph - M 24 |
47.648
(8.7416)
|
TFR Baseline |
48.382
(8.6503)
|
TFR - Month 6 |
46.605
(9.5042)
|
TFR - Month 12 |
46.006
(8.6997)
|
Title | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
all completers did not complete all categories of questionaire |
Arm/Group Title | No Problems | Some Problems | Extreme Problems |
---|---|---|---|
Arm/Group Description | No problems | Some problems | Extreme problems |
Measure Participants | 26 | 26 | 26 |
Number of participants |
22
68.8%
|
4
NaN
|
0
NaN
|
Number of participants |
25
78.1%
|
1
NaN
|
0
NaN
|
Number of participants |
21
65.6%
|
5
NaN
|
0
NaN
|
Number of participants |
12
37.5%
|
13
NaN
|
0
NaN
|
Number of participants |
20
62.5%
|
6
NaN
|
0
NaN
|
Title | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
all completers did not complete all categories of questionaire |
Arm/Group Title | No Problems | Some Problems | Extreme Problems |
---|---|---|---|
Arm/Group Description | No problems | Some problems | Extreme problems |
Measure Participants | 31 | 31 | 31 |
Number of participants |
23
71.9%
|
8
NaN
|
0
NaN
|
Number of participants |
31
96.9%
|
0
NaN
|
0
NaN
|
Number of participants |
23
71.9%
|
7
NaN
|
1
NaN
|
Number of participants |
18
56.3%
|
11
NaN
|
1
NaN
|
Number of participants |
21
65.6%
|
10
NaN
|
0
NaN
|
Title | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
all completers did not complete all categories of questionaire |
Arm/Group Title | No Problems | Some Problems | Extreme Problems |
---|---|---|---|
Arm/Group Description | No problems | Some problems | Extreme problems |
Measure Participants | 28 | 28 | 28 |
Number of participants |
19
59.4%
|
8
NaN
|
0
NaN
|
Number of participants |
28
87.5%
|
0
NaN
|
0
NaN
|
Number of participants |
23
71.9%
|
4
NaN
|
0
NaN
|
Number of participants |
17
53.1%
|
9
NaN
|
2
NaN
|
Number of participants |
19
59.4%
|
8
NaN
|
0
NaN
|
Title | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
all completers did not complete all categories of questionaire |
Arm/Group Title | No Problems | Some Problems | Extreme Problems |
---|---|---|---|
Arm/Group Description | No problems | Some problems | Extreme problems |
Measure Participants | 10 | 10 | 10 |
Number of participants |
7
21.9%
|
3
NaN
|
0
NaN
|
Number of participants |
10
31.3%
|
0
NaN
|
0
NaN
|
Number of participants |
10
31.3%
|
0
NaN
|
0
NaN
|
Number of participants |
5
15.6%
|
4
NaN
|
1
NaN
|
Number of participants |
8
25%
|
2
NaN
|
0
NaN
|
Title | Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
all completers did not complete all categories of questionaire |
Arm/Group Title | No Problems | Some Problems | Extreme Problems |
---|---|---|---|
Arm/Group Description | No problems | Some problems | Extreme problems |
Measure Participants | 5 | 5 | 5 |
Number of participants |
4
12.5%
|
1
NaN
|
0
NaN
|
Number of participants |
5
15.6%
|
0
NaN
|
0
NaN
|
Number of participants |
4
12.5%
|
1
NaN
|
0
NaN
|
Number of participants |
1
3.1%
|
4
NaN
|
0
NaN
|
Number of participants |
3
9.4%
|
2
NaN
|
0
NaN
|
Adverse Events
Time Frame | Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment or last day in TFR Phase up to approximately 5 years | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Nilotinib | |
Arm/Group Description | Nilotinib | |
All Cause Mortality |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 0/59 (0%) | |
Serious Adverse Events |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 19/59 (32.2%) | |
Cardiac disorders | ||
Cardiac failure | 1/59 (1.7%) | |
Coronary artery disease | 1/59 (1.7%) | |
Myocardial infarction | 1/59 (1.7%) | |
Pericardial effusion | 1/59 (1.7%) | |
Gastrointestinal disorders | ||
Abdominal pain | 2/59 (3.4%) | |
Hypoaesthesia oral | 1/59 (1.7%) | |
Small intestinal obstruction | 1/59 (1.7%) | |
General disorders | ||
Chest discomfort | 1/59 (1.7%) | |
Chest pain | 1/59 (1.7%) | |
Device embolisation | 1/59 (1.7%) | |
Ill-defined disorder | 1/59 (1.7%) | |
Non-cardiac chest pain | 1/59 (1.7%) | |
Pyrexia | 1/59 (1.7%) | |
Vascular stent stenosis | 1/59 (1.7%) | |
Infections and infestations | ||
Cellulitis | 1/59 (1.7%) | |
Gastroenteritis | 1/59 (1.7%) | |
Influenza | 1/59 (1.7%) | |
Osteomyelitis | 1/59 (1.7%) | |
Urinary tract infection | 1/59 (1.7%) | |
Wound infection | 1/59 (1.7%) | |
Injury, poisoning and procedural complications | ||
Fall | 1/59 (1.7%) | |
Hip fracture | 1/59 (1.7%) | |
Vascular graft thrombosis | 1/59 (1.7%) | |
Wound dehiscence | 1/59 (1.7%) | |
Musculoskeletal and connective tissue disorders | ||
Compartment syndrome | 1/59 (1.7%) | |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Malignant melanoma | 1/59 (1.7%) | |
Nervous system disorders | ||
Cerebrovascular accident | 1/59 (1.7%) | |
Hypoaesthesia | 1/59 (1.7%) | |
Transient ischaemic attack | 1/59 (1.7%) | |
Vascular headache | 1/59 (1.7%) | |
Renal and urinary disorders | ||
Acute kidney injury | 1/59 (1.7%) | |
Respiratory, thoracic and mediastinal disorders | ||
Bronchospasm | 1/59 (1.7%) | |
Dyspnoea | 1/59 (1.7%) | |
Respiratory failure | 1/59 (1.7%) | |
Skin and subcutaneous tissue disorders | ||
Angioedema | 1/59 (1.7%) | |
Surgical and medical procedures | ||
Leg amputation | 1/59 (1.7%) | |
Vascular disorders | ||
Arterial stenosis | 1/59 (1.7%) | |
Deep vein thrombosis | 1/59 (1.7%) | |
Peripheral arterial occlusive disease | 1/59 (1.7%) | |
Peripheral ischaemia | 1/59 (1.7%) | |
Other (Not Including Serious) Adverse Events |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 59/59 (100%) | |
Cardiac disorders | ||
Palpitations | 3/59 (5.1%) | |
Sinus bradycardia | 3/59 (5.1%) | |
Eye disorders | ||
Dry eye | 4/59 (6.8%) | |
Gastrointestinal disorders | ||
Abdominal discomfort | 4/59 (6.8%) | |
Abdominal distension | 3/59 (5.1%) | |
Abdominal pain | 11/59 (18.6%) | |
Abdominal pain upper | 7/59 (11.9%) | |
Constipation | 17/59 (28.8%) | |
Diarrhoea | 9/59 (15.3%) | |
Dry mouth | 3/59 (5.1%) | |
Dyspepsia | 5/59 (8.5%) | |
Gastrooesophageal reflux disease | 3/59 (5.1%) | |
Nausea | 11/59 (18.6%) | |
Vomiting | 5/59 (8.5%) | |
General disorders | ||
Fatigue | 23/59 (39%) | |
Influenza like illness | 4/59 (6.8%) | |
Oedema peripheral | 5/59 (8.5%) | |
Pain | 3/59 (5.1%) | |
Pyrexia | 4/59 (6.8%) | |
Infections and infestations | ||
Bronchitis | 3/59 (5.1%) | |
Nasopharyngitis | 6/59 (10.2%) | |
Sinusitis | 7/59 (11.9%) | |
Upper respiratory tract infection | 3/59 (5.1%) | |
Urinary tract infection | 5/59 (8.5%) | |
Injury, poisoning and procedural complications | ||
Fall | 3/59 (5.1%) | |
Investigations | ||
Alanine aminotransferase increased | 7/59 (11.9%) | |
Blood bilirubin increased | 4/59 (6.8%) | |
Blood cholesterol increased | 5/59 (8.5%) | |
Lipase increased | 11/59 (18.6%) | |
Weight decreased | 9/59 (15.3%) | |
Metabolism and nutrition disorders | ||
Decreased appetite | 6/59 (10.2%) | |
Diabetes mellitus | 3/59 (5.1%) | |
Hyperglycaemia | 7/59 (11.9%) | |
Hypophosphataemia | 3/59 (5.1%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 12/59 (20.3%) | |
Arthritis | 3/59 (5.1%) | |
Back pain | 7/59 (11.9%) | |
Bone pain | 3/59 (5.1%) | |
Muscle spasms | 4/59 (6.8%) | |
Muscular weakness | 3/59 (5.1%) | |
Musculoskeletal pain | 5/59 (8.5%) | |
Myalgia | 7/59 (11.9%) | |
Pain in extremity | 10/59 (16.9%) | |
Nervous system disorders | ||
Dizziness | 3/59 (5.1%) | |
Headache | 14/59 (23.7%) | |
Psychiatric disorders | ||
Anxiety | 3/59 (5.1%) | |
Depression | 3/59 (5.1%) | |
Insomnia | 6/59 (10.2%) | |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 7/59 (11.9%) | |
Dyspnoea | 5/59 (8.5%) | |
Oropharyngeal pain | 4/59 (6.8%) | |
Skin and subcutaneous tissue disorders | ||
Alopecia | 7/59 (11.9%) | |
Dry skin | 3/59 (5.1%) | |
Pruritus | 11/59 (18.6%) | |
Rash | 16/59 (27.1%) | |
Rash maculo-papular | 7/59 (11.9%) | |
Rash pruritic | 4/59 (6.8%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 888-669-6682 |
Novartis.email@novartis.com |
- CAMN107AUS37