ENESTgoal: A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01744665
Collaborator
(none)
59
54
1
61.6
1.1
0

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

Study Type:
Interventional
Actual Enrollment :
59 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Randomized, Multicenter Study of Treatment-free Remission in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Patients Who Achieve and Sustain MR4.5 After Switching to Nilotinib
Actual Study Start Date :
Aug 12, 2013
Actual Primary Completion Date :
Sep 28, 2018
Actual Study Completion Date :
Sep 29, 2018

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:
  • AMN107
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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

    7. 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).

    8. 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

    9. 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

    10. 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

    11. 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

    12. 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

    13. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    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.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01744665
    Other Study ID Numbers:
    • CAMN107AUS37
    First Posted:
    Dec 7, 2012
    Last Update Posted:
    Mar 10, 2020
    Last Verified:
    Feb 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Novartis Pharmaceuticals

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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%
    4. Secondary Outcome
    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%
    5. Secondary Outcome
    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%
    6. Secondary Outcome
    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%
    7. Secondary Outcome
    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)
    8. Secondary Outcome
    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
    9. Secondary Outcome
    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)
    10. Secondary Outcome
    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
    11. Secondary Outcome
    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
    12. Secondary Outcome
    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
    13. Secondary Outcome
    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
    14. Secondary Outcome
    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

    [Not Specified]

    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
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01744665
    Other Study ID Numbers:
    • CAMN107AUS37
    First Posted:
    Dec 7, 2012
    Last Update Posted:
    Mar 10, 2020
    Last Verified:
    Feb 1, 2020