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
Enrollment
54
Locations
1
Arm
61.6
Actual Duration (Months)
1.1
Patients Per Site
0
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1University of Alabama Comprehensive Cancer Center University of Alabama (8)BirminghamAlabamaUnited States35294
    2Banner MD Anderson Cancer Center Banner MD Anderson (2)GilbertArizonaUnited States85234
    3Scottsdale Healthcare/TGen Clinical Research Service SCScottsdaleArizonaUnited States85258
    4Highlands Oncology GroupFayettevilleArkansasUnited States72703
    5City of Hope National Medical Center Dept of OncologyDuarteCaliforniaUnited States91010 3000
    6Compassionate Care Research Group Inc CCCMGFountain ValleyCaliforniaUnited States92708
    7UC San Diego UC San Diego Cancer CtrLa JollaCaliforniaUnited States92093-0987
    8Wilshire Oncology Medical Group Corona Cancer CenterMultiple LocationsCaliforniaUnited States
    9Epic-CarePleasant HillCaliforniaUnited States94523
    10Sutter Institute for Medical Research Oncology/HematologySacramentoCaliforniaUnited States95816-5199
    11St Joseph Heritage HealthcareSanta RosaCaliforniaUnited States94503
    12Rocky Mountain Cancer Centers USORBoulderColoradoUnited States80304
    13Florida Cancer Specialists DeptofFloridaCancerSpecialistsFort MyersFloridaUnited States33901
    14MD Anderson Cancer Center - Orlando Cancer CenterOrlandoFloridaUnited States32806
    15H Lee Moffitt Cancer Center and Research Institute H. Lee Moffitt Cancer Ctr (67)TampaFloridaUnited States33612
    16Stroger Cook County Hospital Division of Hematology & OncChicagoIllinoisUnited States60612
    17University of Chicago Medical CenterChicagoIllinoisUnited States60637
    18University of Iowa Hospitals and Clinics Holden Comprehensive Cancer CtIowa CityIowaUnited States52242
    19University of Kansas Hospital and Medical Center Clinical Research CenterKansas CityKansasUnited States66160
    20Cancer Center of KansasWichitaKansasUnited States67214-3728
    21Christus Schumpert Health SystemShreveportLouisianaUnited States71101
    22Michigan State University / Breslin Cancer Center Breslin Cancer Center (3)LansingMichiganUnited States
    23Billings Clinic Billings Clinic (8)Billings MontanaMontanaUnited States59101
    24Hackensack University Medical Center John Theurer Cancer CenterHackensackNew JerseyUnited States07601
    25Hematology Oncology Associates of Northern New Jersey PA Dept of Hem-Onc of Northern NJMorristownNew JerseyUnited States07962
    26Montefiore Medical Center Montefiore Medicial CenterBronxNew YorkUnited States10467
    27Memorial Sloan Kettering Memorial Sloan Kettering (63)New YorkNew YorkUnited States10017
    28Weill Cornell Medical Center Dept. of OncologyNew YorkNew YorkUnited States10021
    29Columbia University Medical Center Herbert Irving PavilionNew YorkNew YorkUnited States10032
    30University of Rochester Medical CenterRochesterNew YorkUnited States14642
    31Westchester Medical Center NY Medical CollegeValhallaNew YorkUnited States10595
    32Duke University Medical Center Duke University Med CtrDurhamNorth CarolinaUnited States27710
    33Carolina Oncology Specialists, PCHickoryNorth CarolinaUnited States28602
    34Wake Forest University Health Sciences Hematology and OncologyWinston-SalemNorth CarolinaUnited States27157
    35Ohio State Comprehensive Cancer Center/James Cancer Hospital OSU Medical CenterColumbusOhioUnited States43210
    36Northwest Cancer Specialists Compass Oncology -BKMPortlandOregonUnited States97210
    37University of South Carolina-Hollings Cancer Center Medical University of SCColumbiaSouth CarolinaUnited States29203
    38Tennessee Oncology Dept. of Centennial MedicalNashvilleTennesseeUnited States37203
    39Vanderbilt Univeristy Ingram Cancer Center (10)NashvilleTennesseeUnited States37232
    40Hendrick Cancer Center Hendricks Cancer CenterAbileneTexasUnited States79601
    41Texas Oncology Texas Oncology - McAllenDallasTexasUnited States75246
    42Texas Oncology Texas Oncology - Plano WestDallasTexasUnited States75246
    43Texas Oncology P A Texas Oncology - MidlandDallasTexasUnited States75251
    44University of Texas Medical Branch SCGalvestonTexasUnited States77555-1188
    45Oncology Consultants Oncology Consultants, P.A.HoustonTexasUnited States77024
    46The Methodist Hospital Cornell UniversityHoustonTexasUnited States77030
    47South Texas Cancer Center- McAllenMcAllenTexasUnited States78503
    48Brooke Army Medical Center Brooke Army MedicalSan AntonioTexasUnited States78234
    49Waco Cancer and Research CenterWacoTexasUnited States76712
    50University of Utah / Huntsman Cancer Institute Huntsman Cancer CenterSalt Lake CityUtahUnited States84103
    51University of VirginiaCharlottesvilleVirginiaUnited States22908
    52Kadlec Clinic Hematology and Oncology SCKennewickWashingtonUnited States99336
    53West Virginia University/ Mary Babb Randolph Cancer Center Mary Babb Randolph Cancer CtrMorgantownWest VirginiaUnited States26506
    54Medical College of Wisconsin Med College of WIMilwaukeeWisconsinUnited States53226

    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 TitleNilotinib
    Arm/Group DescriptionAll patients enrolled in trial
    Period Title: Monitoring Phase
    STARTED59
    COMPLETED41
    NOT COMPLETED18
    Period Title: Monitoring Phase
    STARTED41
    COMPLETED22
    NOT COMPLETED19
    Period Title: Monitoring Phase
    STARTED32
    COMPLETED32
    NOT COMPLETED0
    Period Title: Monitoring Phase
    STARTED17
    COMPLETED4
    NOT COMPLETED13

    Baseline Characteristics

    Arm/Group TitleOverall
    Arm/Group DescriptionPatients 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 Participants32
    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
    TitlePercentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase
    DescriptionPercentage 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 Frame6 months after stopping nilotinib therapy

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants32
    Number of participants
    12
    37.5%
    2. Secondary Outcome
    TitleRelapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5).
    DescriptionRelapse-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 Frame7 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants32
    Median (95% Confidence Interval) [weeks]
    21.4
    3. Secondary Outcome
    TitlePercentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase
    DescriptionThe 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 Frame12 and 24 months after starting the TFR

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants32
    Number of participants
    8
    25%
    Number of participants
    2
    6.3%
    4. Secondary Outcome
    TitlePercentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse
    DescriptionThe 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 FrameRestart of nilotinib up to month 6, 12 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants17
    Number of participants
    7
    21.9%
    Number of participants
    17
    53.1%
    Number of participants
    17
    53.1%
    5. Secondary Outcome
    TitleNumber of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause.
    DescriptionProgression to AP/BC and death where the "failure" event is the earliest occurrence of the following event: progression to AP/BC date.
    Time FrameBaseline up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants32
    Number [participants]
    0
    0%
    6. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS was defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.
    Time FrameBaseline up to approximately 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants32
    Number [participants]
    0
    0%
    7. Secondary Outcome
    TitleChange in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment
    DescriptionThe 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 FrameFrom 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 TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants59
    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
    TitleChange in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set
    DescriptionThe 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 FrameFrom 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 TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants36
    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
    TitleChange in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set
    DescriptionThe 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 FrameFrom 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 TitleTreatment Free Remission
    Arm/Group DescriptionPatients 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 Participants41
    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
    TitlePercentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set
    DescriptionThe 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 FrameAt month 3 in Consolidation Phase

    Outcome Measure Data

    Analysis Population Description
    all completers did not complete all categories of questionaire
    Arm/Group TitleNo ProblemsSome ProblemsExtreme Problems
    Arm/Group DescriptionNo problemsSome problemsExtreme problems
    Measure Participants262626
    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
    TitlePercentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set
    DescriptionThe 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 FrameMonth 12 in Consolidation Phase

    Outcome Measure Data

    Analysis Population Description
    all completers did not complete all categories of questionaire
    Arm/Group TitleNo ProblemsSome ProblemsExtreme Problems
    Arm/Group DescriptionNo problemsSome problemsExtreme problems
    Measure Participants313131
    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
    TitlePercentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set
    DescriptionThe 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 FrameMonth 24 in Consolidation Phase

    Outcome Measure Data

    Analysis Population Description
    all completers did not complete all categories of questionaire
    Arm/Group TitleNo ProblemsSome ProblemsExtreme Problems
    Arm/Group DescriptionNo problemsSome problemsExtreme problems
    Measure Participants282828
    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
    TitlePercentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set
    DescriptionThe 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 FrameMonth 6 in in Treatment Free Remission Phase

    Outcome Measure Data

    Analysis Population Description
    all completers did not complete all categories of questionaire
    Arm/Group TitleNo ProblemsSome ProblemsExtreme Problems
    Arm/Group DescriptionNo problemsSome problemsExtreme problems
    Measure Participants101010
    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
    TitlePercentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set
    DescriptionThe 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 FrameMonth 12 in in Treatment Free Remission Phase

    Outcome Measure Data

    Analysis Population Description
    all completers did not complete all categories of questionaire
    Arm/Group TitleNo ProblemsSome ProblemsExtreme Problems
    Arm/Group DescriptionNo problemsSome problemsExtreme problems
    Measure Participants555
    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 FrameAdverse 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 TitleNilotinib
    Arm/Group DescriptionNilotinib
    All Cause Mortality
    Nilotinib
    Affected / at Risk (%)# Events
    Total0/59 (0%)
    Serious Adverse Events
    Nilotinib
    Affected / at Risk (%)# Events
    Total19/59 (32.2%)
    Cardiac disorders
    Cardiac failure1/59 (1.7%)
    Coronary artery disease1/59 (1.7%)
    Myocardial infarction1/59 (1.7%)
    Pericardial effusion1/59 (1.7%)
    Gastrointestinal disorders
    Abdominal pain2/59 (3.4%)
    Hypoaesthesia oral1/59 (1.7%)
    Small intestinal obstruction1/59 (1.7%)
    General disorders
    Chest discomfort1/59 (1.7%)
    Chest pain1/59 (1.7%)
    Device embolisation1/59 (1.7%)
    Ill-defined disorder1/59 (1.7%)
    Non-cardiac chest pain1/59 (1.7%)
    Pyrexia1/59 (1.7%)
    Vascular stent stenosis1/59 (1.7%)
    Infections and infestations
    Cellulitis1/59 (1.7%)
    Gastroenteritis1/59 (1.7%)
    Influenza1/59 (1.7%)
    Osteomyelitis1/59 (1.7%)
    Urinary tract infection1/59 (1.7%)
    Wound infection1/59 (1.7%)
    Injury, poisoning and procedural complications
    Fall1/59 (1.7%)
    Hip fracture1/59 (1.7%)
    Vascular graft thrombosis1/59 (1.7%)
    Wound dehiscence1/59 (1.7%)
    Musculoskeletal and connective tissue disorders
    Compartment syndrome1/59 (1.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma1/59 (1.7%)
    Nervous system disorders
    Cerebrovascular accident1/59 (1.7%)
    Hypoaesthesia1/59 (1.7%)
    Transient ischaemic attack1/59 (1.7%)
    Vascular headache1/59 (1.7%)
    Renal and urinary disorders
    Acute kidney injury1/59 (1.7%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm1/59 (1.7%)
    Dyspnoea1/59 (1.7%)
    Respiratory failure1/59 (1.7%)
    Skin and subcutaneous tissue disorders
    Angioedema1/59 (1.7%)
    Surgical and medical procedures
    Leg amputation1/59 (1.7%)
    Vascular disorders
    Arterial stenosis1/59 (1.7%)
    Deep vein thrombosis1/59 (1.7%)
    Peripheral arterial occlusive disease1/59 (1.7%)
    Peripheral ischaemia1/59 (1.7%)
    Other (Not Including Serious) Adverse Events
    Nilotinib
    Affected / at Risk (%)# Events
    Total59/59 (100%)
    Cardiac disorders
    Palpitations3/59 (5.1%)
    Sinus bradycardia3/59 (5.1%)
    Eye disorders
    Dry eye4/59 (6.8%)
    Gastrointestinal disorders
    Abdominal discomfort4/59 (6.8%)
    Abdominal distension3/59 (5.1%)
    Abdominal pain11/59 (18.6%)
    Abdominal pain upper7/59 (11.9%)
    Constipation17/59 (28.8%)
    Diarrhoea9/59 (15.3%)
    Dry mouth3/59 (5.1%)
    Dyspepsia5/59 (8.5%)
    Gastrooesophageal reflux disease3/59 (5.1%)
    Nausea11/59 (18.6%)
    Vomiting5/59 (8.5%)
    General disorders
    Fatigue23/59 (39%)
    Influenza like illness4/59 (6.8%)
    Oedema peripheral5/59 (8.5%)
    Pain3/59 (5.1%)
    Pyrexia4/59 (6.8%)
    Infections and infestations
    Bronchitis3/59 (5.1%)
    Nasopharyngitis6/59 (10.2%)
    Sinusitis7/59 (11.9%)
    Upper respiratory tract infection3/59 (5.1%)
    Urinary tract infection5/59 (8.5%)
    Injury, poisoning and procedural complications
    Fall3/59 (5.1%)
    Investigations
    Alanine aminotransferase increased7/59 (11.9%)
    Blood bilirubin increased4/59 (6.8%)
    Blood cholesterol increased5/59 (8.5%)
    Lipase increased11/59 (18.6%)
    Weight decreased9/59 (15.3%)
    Metabolism and nutrition disorders
    Decreased appetite6/59 (10.2%)
    Diabetes mellitus3/59 (5.1%)
    Hyperglycaemia7/59 (11.9%)
    Hypophosphataemia3/59 (5.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia12/59 (20.3%)
    Arthritis3/59 (5.1%)
    Back pain7/59 (11.9%)
    Bone pain3/59 (5.1%)
    Muscle spasms4/59 (6.8%)
    Muscular weakness3/59 (5.1%)
    Musculoskeletal pain5/59 (8.5%)
    Myalgia7/59 (11.9%)
    Pain in extremity10/59 (16.9%)
    Nervous system disorders
    Dizziness3/59 (5.1%)
    Headache14/59 (23.7%)
    Psychiatric disorders
    Anxiety3/59 (5.1%)
    Depression3/59 (5.1%)
    Insomnia6/59 (10.2%)
    Respiratory, thoracic and mediastinal disorders
    Cough7/59 (11.9%)
    Dyspnoea5/59 (8.5%)
    Oropharyngeal pain4/59 (6.8%)
    Skin and subcutaneous tissue disorders
    Alopecia7/59 (11.9%)
    Dry skin3/59 (5.1%)
    Pruritus11/59 (18.6%)
    Rash16/59 (27.1%)
    Rash maculo-papular7/59 (11.9%)
    Rash pruritic4/59 (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/TitleStudy Director
    OrganizationNovartis Pharmaceuticals
    Phone888-669-6682
    EmailNovartis.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