ENESTPath: A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML.

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01743989
Collaborator
(none)
620
Enrollment
208
Locations
3
Arms
86.8
Actual Duration (Months)
3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study aimed to assess the optimal duration of nilotinib 300 mg twice daily (BID) consolidation treatment in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), in order that patients remained in treatment-free remission (≥MR4.0) without molecular relapse 12 months after starting the Treatment-Free Remission (TFR) phase.

Detailed Description

This was a prospective, randomized, open-label, multicenter Phase III study. The study design was made up of 3 phases:

  • Nilotinib induction phase: 12 months

  • Nilotinib consolidation phase: 12 or 24 months, depending on randomization

  • Nilotinib treatment-free remission (TFR) phase: 24 or 36 months, depending on randomization.

Subjects were enrolled into the study and were treated with nilotinib 300mg twice daily (BID) for 24 months, during the induction (12 months) and consolidation (12 months) phases. At the end of the first 24 months of treatment, participants achieving a sustained molecular response (defined as ≥ MR4.0, in 4 out of 5 real-time quantitative polymerase chain reaction (RQ-PCR) assessments, including the last assessment, in the last 12 months) were randomized on a 1:1 basis to either:

  1. suspend nilotinib treatment immediately and enter the TFR phase for 36 months (Nilotinib 24-month treatment arm), or

  2. continue nilotinib treatment for a further 12 months (post-randomization consolidation phase), then suspend treatment and enter the TFR phase for 24 months (Nilotinib 36-month treatment arm).

Participants not achieving a sustained molecular response at 24 months from treatment start were not eligible for randomization and were treated at the discretion of the investigator according to standard practice. Information on survival, stem cell transplantation, and status of the patient's disease was collected until death or until 5 years from study entry, whichever came first. Additionally, for Nilotinib 36-month treatment arm, participants who did not achieve a sustained molecular response at 36 months from treatment start, discontinued from the study and were treated according to standard practice and followed up until death or until 5 years from study entry, whichever came first.

Participants relapsing during the TFR phase entered the nilotinib re-treatment phase of the study, and were re-treated with the same dose of nilotinib as they were on before the TFR phase. These patients remained on study until the completion of the 5-year study period unless prematurely withdrawn and discontinued from the study for any reason specified in the Protocol.

Study Design

Study Type:
Interventional
Actual Enrollment :
620 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
All participants received 24 months of study treatment. After 24 months of treatment, eligible participants (i.e. those deemed to have achieved sustained molecular response) were randomized to one of the two study arms on a continued open-label basis. Participants not achieving sustained molecular response after 24 months of treatment were not randomized but remained in the study until the 5-year study period was completed (Not randomized arm).All participants received 24 months of study treatment. After 24 months of treatment, eligible participants (i.e. those deemed to have achieved sustained molecular response) were randomized to one of the two study arms on a continued open-label basis. Participants not achieving sustained molecular response after 24 months of treatment were not randomized but remained in the study until the 5-year study period was completed (Not randomized arm).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Prospective, Randomized, Open Label, Two Arm Phase III Study to Evaluate Treatment Free Remission (TFR) Rate in Patients With Philadelphia-positive CML After Two Different Durations of Consolidation Treatment With Nilotinib 300mg BID.
Actual Study Start Date :
Apr 15, 2013
Actual Primary Completion Date :
Jul 8, 2020
Actual Study Completion Date :
Jul 8, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nilotinib 24-month treatment

Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase

Drug: Nilotinib
Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.
Other Names:
  • AMN107
  • Experimental: Nilotinib 36-month treatment

    Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase

    Drug: Nilotinib
    Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.
    Other Names:
  • AMN107
  • Experimental: Not randomized

    Participants were treated with nolotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment.

    Drug: Nilotinib
    Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.
    Other Names:
  • AMN107
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase [12 months after entering the TFR phase, which is after 36 months from study treatment start for Nilotinib 24-month treatment arm and after 48 months from study treatment start for Nilotinib 36-month treatment arm]

      Number of participants who remained in TFR (≥molecular response (MR) 4.0) without molecular relapse 12 months after entering the TFR phase (without re-starting nilotinib therapy) divided by the number of participants who entered the TFR phase and multiplied by 100. Molecular relapse during TFR is defined as the loss of major molecular response (MMR), or the confirmed loss of MR4.0 (defined by 3 consecutive tests less than MR4.0 assessed at 3 consecutive visits during TFR phase). Participants dropping out early from the study during the TFR phase were considered as unsuccessful TFR. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL. MR4.0 is defined as either detectable disease≤0.01% BCR-ABL or undetectable disease in cDNA with≥10,000 ABL transcripts

    Secondary Outcome Measures

    1. Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry [From baseline up to 24 months after study treatment start]

      Number of participants who were in MMR during pre-randomization induction/consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.

    2. Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry [From randomization (month 24 after study treatment start) up to 36 months after study treatment start]

      Number of participants who were in MMR during post-randomization consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.

    3. Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry [From baseline up to 24 months after study treatment start]

      Number of participants who were in MR4.0 during the pre-randomization induction/consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    4. Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry [From randomization (month 24 after study treatment start) up to 36 months after study treatment start]

      Number of participants who were in MR4.0 during the post-randomization consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    5. Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry [From baseline up to 24 months after study treatment start]

      Number of participants who were in MR4.5 during the pre-randomization induction/consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    6. Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry [From randomization (month 24 after study treatment start) up to 36 months after study treatment start]

      Number of participants who were in MR4.5 during the post-randomization consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    7. Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase [From baseline up to 24 months after study treatment start]

      Number of participants who were in MMR during the pre-randomization induction/consolidation phase divided by the number of enrolled participants and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.

    8. Cumulative Incidence of MMR During the Post-randomization Consolidation Phase [From randomization (month 24 after study treatment start) up to 36 months after study treatment start]

      Number of participants who were in MMR during the post-randomization consolidation phase divided by the number of enrolled participants and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.

    9. Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase [From baseline up to 24 months after study treatment start]

      Number of participants who were in MR4.0 during the pre-randomization induction/consolidation phase divided by the number of enrolled participants and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    10. Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase [From randomization (month 24 after study treatment start) up to 36 months after study treatment start]

      Number of participants who were in MR4.0 during the post-randomization consolidation phase divided by the number of enrolled participants and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    11. Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase [From baseline up to 24 months after study treatment start]

      Number of participants who were in MR4.5 during the pre-randomization induction/consolidation phase divided by the number of enrolled participants and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    12. Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase [From randomization (month 24 after study treatment start) up to 36 months after study treatment start]

      Number of participants who were in MR4.5 during the post-randomization consolidation phase divided by the number of enrolled participants and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    13. Percentage of Participants Who Were in MMR During TFR Phase [From Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm]

      Number of participants who were in MMR at selected timepoints divided by the number of participants in the TFR phase and multiplied by 100. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.

    14. Percentage of Participants Who Were in MR4.0 During the TFR Phase [From Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotininb 36-months treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-months treatment arm]

      Number of participants who were in MR4.0 at selected timepoints divided by the number of participants in the TFR phase and multiplied by 100. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    15. Percentage of Participants Who Were in MR4.5 During the TFR Phase [From Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotininb 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm]

      Number of participants who were in MR4.5 at selected timepoints divided by the number of participants in the TFR phase and multiplied by 100. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    16. BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase [From baseline up to 24 months after study treatment start for Nilotinib 24-month treatment arm and Not randomized participants; and up to 36 months after study treatment start for Nilotinib 36-month treatment arm.]

      BCR-ABL transcript ratio by international scale (IS) (expressed as a percentage) during the induction/consolidation phase. Participants randomized to Nilotinib 36-month treatment arm had 12-month additional consolidation phase (post-randomization).

    17. BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase [From Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm]

      BCR-ABL/control gene (ABL) transcript ratio by international scale (IS) (expressed as a percentage) during the TFR phase. BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase.

    18. BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase [From Day 1 after entering the re-treatment phase up to 24 months after entering re-treatment phase for Nilotinib 36-month treatment arm and 36 months after entering the re-treatment phase for Nilotinib 24-month treatment arm]

      BCR-ABL/control gene (ABL) transcript ratio by international scale (IS) (expressed as a percentage) during the nilotinib re-treatment phase. BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes.

    19. Progression-free Survival (PFS) During the TFR Phase of the Study. [From the start of the TFR phase to progression to AP/BC or death up to 24 months after entering TFR phase for Nilotininb 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm]

      PFS is defined as the time from the date of start of the nilotinib TFR phase to the date of acelerated phase/blast crisis (AP/BC) or death, whichever came first. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotini 24-month treatment arm had a maximum of 36 months of TFR phase. Patients not known to have recurred or died on or before the cut-off date for PFS analysis were censored at the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who were on study, and at the date of last contact for patients who were in follow-up.

    20. Treatment -Free Survival (TFS) During the TFR Phase of the Study [From the start of the TFR phase to the date of occurrence of treatment-free survival event, up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm]

      TFS is defined as the time from the start of the TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4.0,re-start of nilotinib treatment, progression to AP/BC, or death from any cause. Patients not known to have had any of the events on or before the cut-off date were censored at the earlier of the date of their last assessment for patients who were still on study and the date of last contact for patients who were in follow-up. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1%BCR-ABL. MR4.0 is defined as either detectable disease ≤0.01%BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)

    21. Overall Survival (OS) Rate During the TFR Phase of the Study. [From the start of the TFR phase to death due to any cause, assessed up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm]

      OS is defined as the time from start of the TFR phase to the time of death due to any cause. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotini 24-month treatment arm had a maximum of 36 months of TFR phase. For participants without any event on or before the cut-off date, survival time will be censored at the date of their last assessment for patients who are still on study, and at the date of last contact for patients who are in follow-up.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Confirmed diagnosis of chronic phase Ph+ CML

    • Previous first-line treatment with imatinib for a minimum of 2 years;

    • Patient in complete cytogenetic response;

    Key Exclusion Criteria:
    • Previous achievement of MR4.0 at study entry;

    • Previous treatment with other target cells inhibitors other than imatinib;

    • Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;

    • Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;

    • Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol;

    • History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively;

    • Patients who have not recovered from prior surgery;

    • Treatment with other investigational agents within 4 weeks of Day 1;

    • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug

    Other inclusion/exclusion criteria might apply.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Novartis Investigative SiteLinzOberoesterreichAustriaA 4020
    2Novartis Investigative SiteGrazAustria8036
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    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:
    NCT01743989
    Other Study ID Numbers:
    • CAMN107AIC05
    • 2012-005124-15
    First Posted:
    Dec 6, 2012
    Last Update Posted:
    Jul 15, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailFor one participant randomized to Nilotinib 36-month treatment arm, the informed consent was not obtained prior to any study specific procedure. This participant discontinued the study before entering the TFR phase.
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Period Title: Treatment Phase
    STARTED120119381
    Participants Who Signed Informed Consent120118381
    COMPLETED1191040
    NOT COMPLETED115381
    Period Title: Treatment Phase
    STARTED1191040
    COMPLETED37360
    NOT COMPLETED82680
    Period Title: Treatment Phase
    STARTED74550
    COMPLETED58460
    NOT COMPLETED1690

    Baseline Characteristics

    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot RandomizedTotal
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.Total of all reporting groups
    Overall Participants120119381620
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    106
    88.3%
    98
    82.4%
    308
    80.8%
    512
    82.6%
    >=65 years
    14
    11.7%
    21
    17.6%
    73
    19.2%
    108
    17.4%
    Sex: Female, Male (Count of Participants)
    Female
    48
    40%
    49
    41.2%
    129
    33.9%
    226
    36.5%
    Male
    72
    60%
    70
    58.8%
    252
    66.1%
    394
    63.5%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    114
    95%
    112
    94.1%
    355
    93.2%
    581
    93.7%
    Black
    0
    0%
    1
    0.8%
    4
    1%
    5
    0.8%
    Asian
    0
    0%
    0
    0%
    2
    0.5%
    2
    0.3%
    Native American
    0
    0%
    1
    0.8%
    1
    0.3%
    2
    0.3%
    North African descent
    1
    0.8%
    0
    0%
    1
    0.3%
    2
    0.3%
    Unknown
    0
    0%
    1
    0.8%
    5
    1.3%
    6
    1%
    Other
    5
    4.2%
    4
    3.4%
    13
    3.4%
    22
    3.5%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase
    DescriptionNumber of participants who remained in TFR (≥molecular response (MR) 4.0) without molecular relapse 12 months after entering the TFR phase (without re-starting nilotinib therapy) divided by the number of participants who entered the TFR phase and multiplied by 100. Molecular relapse during TFR is defined as the loss of major molecular response (MMR), or the confirmed loss of MR4.0 (defined by 3 consecutive tests less than MR4.0 assessed at 3 consecutive visits during TFR phase). Participants dropping out early from the study during the TFR phase were considered as unsuccessful TFR. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL. MR4.0 is defined as either detectable disease≤0.01% BCR-ABL or undetectable disease in cDNA with≥10,000 ABL transcripts
    Time Frame12 months after entering the TFR phase, which is after 36 months from study treatment start for Nilotinib 24-month treatment arm and after 48 months from study treatment start for Nilotinib 36-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Number (95% Confidence Interval) [Percentage of participants]
    31.9
    26.6%
    37.5
    31.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Nilotinib 24-month Treatment, Nilotinib 36-month Treatment
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.383
    Comments
    MethodChi-squared
    Comments
    2. Secondary Outcome
    TitleCumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
    DescriptionNumber of participants who were in MMR during pre-randomization induction/consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.
    Time FrameFrom baseline up to 24 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MMR at baseline
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants231698
    Up to 3 months after study treatment start (pre-randomization)
    69.6
    58%
    37.5
    31.5%
    29.6
    7.8%
    Up to 6 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    64.3
    16.9%
    Up to 9 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    71.4
    18.7%
    Up to 12 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    77.6
    20.4%
    Up to 15 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    80.6
    21.2%
    Up to 18 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    82.7
    21.7%
    Up to 21 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    85.7
    22.5%
    Up to 24 months after study treatment start (pre-randomization)
    100
    83.3%
    100.0
    84%
    86.7
    22.8%
    3. Secondary Outcome
    TitleCumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
    DescriptionNumber of participants who were in MMR during post-randomization consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.
    Time FrameFrom randomization (month 24 after study treatment start) up to 36 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MMR at baseline. Only participants randomized to Nilotinib 36-month treatment arm entered the post-randomization consolidation phase.
    Arm/Group TitleNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants16
    Up to 27 months after study treatment start (post-randomization)
    100.0
    83.3%
    Up to 30 months after study treatment start (post-randomization)
    100.0
    83.3%
    Up to 33 months after study treatment start (post-randomization)
    100.0
    83.3%
    Up to 36 months after study treatment start (post-randomization)
    100.0
    83.3%
    4. Secondary Outcome
    TitleCumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
    DescriptionNumber of participants who were in MR4.0 during the pre-randomization induction/consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom baseline up to 24 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MR4.0 at baseline
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants9294357
    Up to 3 months after study treatment start (pre-randomization)
    48.9
    40.8%
    38.3
    32.2%
    12.9
    3.4%
    Up to 6 months after study treatment start (pre-randomization)
    85.9
    71.6%
    81.9
    68.8%
    26.6
    7%
    Up to 9 months after study treatment start (pre-randomization)
    94.6
    78.8%
    92.6
    77.8%
    34.5
    9.1%
    Up to 12 months after study treatment start (pre-randomization)
    96.7
    80.6%
    98.9
    83.1%
    39.2
    10.3%
    Up to 15 months after study treatment start (pre-randomization)
    100.0
    83.3%
    98.9
    83.1%
    42.0
    11%
    Up to 18 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    45.1
    11.8%
    Up to 21 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    48.7
    12.8%
    Up to 24 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    52.1
    13.7%
    5. Secondary Outcome
    TitleCumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
    DescriptionNumber of participants who were in MR4.0 during the post-randomization consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom randomization (month 24 after study treatment start) up to 36 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MR4.0 at baseline. Only participants randomized to Nilotinib 36-month treatment arm entered the post-randomization consolidation phase
    Arm/Group TitleNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants94
    Up to 27 months after study treatment start (post-randomization)
    97.9
    81.6%
    Up to 30 months after study treatment start (post-randomization)
    97.9
    81.6%
    Up to 33 months after study treatment start (post-randomization)
    97.9
    81.6%
    Up to 36 months after study treatment start (post-randomization)
    97.9
    81.6%
    6. Secondary Outcome
    TitleCumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
    DescriptionNumber of participants who were in MR4.5 during the pre-randomization induction/consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom baseline up to 24 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MR4.5 at baseline
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants109109374
    Up to 3 months after study treatment start (pre-randomization)
    21.1
    17.6%
    17.4
    14.6%
    4.0
    1%
    Up to 6 months after study treatment start (pre-randomization)
    38.5
    32.1%
    38.5
    32.4%
    8.6
    2.3%
    Up to 9 months after study treatment start (pre-randomization)
    57.8
    48.2%
    54.1
    45.5%
    10.7
    2.8%
    Up to 12 months after study treatment start (pre-randomization)
    70.6
    58.8%
    65.1
    54.7%
    14.2
    3.7%
    Up to 15 months after study treatment start (pre-randomization)
    79.8
    66.5%
    76.1
    63.9%
    15.2
    4%
    Up to 18 months after study treatment start (pre-randomization)
    83.5
    69.6%
    80.7
    67.8%
    16.6
    4.4%
    Up to 21 months after study treatment start (pre-randomization)
    85.3
    71.1%
    84.4
    70.9%
    18.4
    4.8%
    Up to 24 months after study treatment start (pre-randomization)
    89.0
    74.2%
    89.0
    74.8%
    20.3
    5.3%
    7. Secondary Outcome
    TitleCumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
    DescriptionNumber of participants who were in MR4.5 during the post-randomization consolidation phase divided by the number of participants without that response at baseline and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom randomization (month 24 after study treatment start) up to 36 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MR4.5 at baseline. Only participants randomized to Nilotinib 36-month treatment arm entered the post-randomization consolidation phase
    Arm/Group TitleNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants109
    Up to 27 months after study treatment start (post-randomization)
    70.6
    58.8%
    Up to 30 months after study treatment start (post-randomization)
    76.1
    63.4%
    Up to 33 months after study treatment start (post-randomization)
    84.4
    70.3%
    Up to 36 months after study treatment start (post-randomization)
    87.2
    72.7%
    8. Secondary Outcome
    TitleCumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase
    DescriptionNumber of participants who were in MMR during the pre-randomization induction/consolidation phase divided by the number of enrolled participants and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.
    Time FrameFrom baseline up to 24 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants120118381
    Baseline
    80.8
    67.3%
    86.4
    72.6%
    74.3
    19.5%
    Up to 3 months after study treatment start (pre-randomization)
    94.2
    78.5%
    91.5
    76.9%
    81.9
    21.5%
    Up to 6 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    90.8
    23.8%
    Up to 9 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    92.7
    24.3%
    Up to 12 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    94.2
    24.7%
    Up to 15 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    95.0
    24.9%
    Up to 18 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    95.5
    25.1%
    Up to 21 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    96.3
    25.3%
    Up to 24 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    96.6
    25.4%
    9. Secondary Outcome
    TitleCumulative Incidence of MMR During the Post-randomization Consolidation Phase
    DescriptionNumber of participants who were in MMR during the post-randomization consolidation phase divided by the number of enrolled participants and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.
    Time FrameFrom randomization (month 24 after study treatment start) up to 36 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure. Only participants randomized to Nilotinib 36-month treatment arm entered the post-randomization consolidation phase
    Arm/Group TitleNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants118
    Up to 27 months after study treatment start (post-randomization)
    98.3
    81.9%
    Up to 30 months after study treatment start (post-randomization)
    98.3
    81.9%
    Up to 33 months after study treatment start (post-randomization)
    98.3
    81.9%
    Up to 36 months after study treatment start (post-randomization)
    98.3
    81.9%
    10. Secondary Outcome
    TitleCumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase
    DescriptionNumber of participants who were in MR4.0 during the pre-randomization induction/consolidation phase divided by the number of enrolled participants and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom baseline up to 24 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants120118381
    Baseline
    23.3
    19.4%
    20.3
    17.1%
    6.3
    1.7%
    Up to 3 months after study treatment start (pre-randomization)
    60.8
    50.7%
    50.8
    42.7%
    18.4
    4.8%
    Up to 6 months after study treatment start (pre-randomization)
    89.2
    74.3%
    85.6
    71.9%
    31.2
    8.2%
    Up to 9 months after study treatment start (pre-randomization)
    95.8
    79.8%
    94.1
    79.1%
    38.6
    10.1%
    Up to 12 months after study treatment start (pre-randomization)
    97.5
    81.3%
    99.2
    83.4%
    43.0
    11.3%
    Up to 15 months after study treatment start (pre-randomization)
    100.0
    83.3%
    99.2
    83.4%
    45.7
    12%
    Up to 18 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    48.6
    12.8%
    Up to 21 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    52.0
    13.6%
    Up to 24 months after study treatment start (pre-randomization)
    100.0
    83.3%
    100.0
    84%
    55.1
    14.5%
    11. Secondary Outcome
    TitleCumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase
    DescriptionNumber of participants who were in MR4.0 during the post-randomization consolidation phase divided by the number of enrolled participants and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom randomization (month 24 after study treatment start) up to 36 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure. Only participants randomized to Nilotinib 36-month treatment arm entered the post-randomization consolidation phase.
    Arm/Group TitleNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants118
    Up to 27 months after study treatment start (post-randomization)
    98.3
    81.9%
    Up to 30 months after study treatment start (post-randomization)
    98.3
    81.9%
    Up to 33 months after study treatment start (post-randomization)
    98.3
    81.9%
    Up to 36 months after study treatment start (post-randomization)
    98.3
    81.9%
    12. Secondary Outcome
    TitleCumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase
    DescriptionNumber of participants who were in MR4.5 during the pre-randomization induction/consolidation phase divided by the number of enrolled participants and multiplied by 100. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom baseline up to 24 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained before any study specific procedure
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants120118381
    Baseline
    9.2
    7.7%
    7.6
    6.4%
    1.8
    0.5%
    Up to 3 months after study treatment start (pre-randomization)
    28.3
    23.6%
    23.7
    19.9%
    5.8
    1.5%
    Up to 6 months after study treatment start (pre-randomization)
    44.2
    36.8%
    43.2
    36.3%
    10.2
    2.7%
    Up to 9 months after study treatment start (pre-randomization)
    61.7
    51.4%
    57.6
    48.4%
    12.3
    3.2%
    Up to 12 months after study treatment start (pre-randomization)
    73.3
    61.1%
    67.8
    57%
    15.7
    4.1%
    Up to 15 months after study treatment start (pre-randomization)
    81.7
    68.1%
    78.0
    65.5%
    16.8
    4.4%
    Up to 18 months after study treatment start (pre-randomization)
    85.0
    70.8%
    82.2
    69.1%
    18.1
    4.8%
    Up to 21 months after study treatment start (pre-randomization)
    86.7
    72.3%
    85.6
    71.9%
    19.9
    5.2%
    Up to 24 months after study treatment start (pre-randomization)
    90.0
    75%
    89.8
    75.5%
    21.8
    5.7%
    13. Secondary Outcome
    TitleCumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase
    DescriptionNumber of participants who were in MR4.5 during the post-randomization consolidation phase divided by the number of enrolled participants and multiplied by 100. Post-randomization consolidation phase corresponded to the 12-month additional treatment (after randomization) for Nilotinib 36-month treatment arm. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom randomization (month 24 after study treatment start) up to 36 months after study treatment start

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained before any study specific procedure. Only participants randomized to Nilotinib 36-month treatment arm entered the post-randomization consolidation phase.
    Arm/Group TitleNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants118
    Up to 27 months after study treatment start (post-randomization)
    72.9
    60.8%
    Up to 30 months after study treatment start (post-randomization)
    78.0
    65%
    Up to 33 months after study treatment start (post-randomization)
    85.6
    71.3%
    Up to 36 months after study treatment start (post-randomization)
    88.1
    73.4%
    14. Secondary Outcome
    TitlePercentage of Participants Who Were in MMR During TFR Phase
    DescriptionNumber of participants who were in MMR at selected timepoints divided by the number of participants in the TFR phase and multiplied by 100. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1% BCR-ABL.
    Time FrameFrom Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Month 1 after entering TFR phase
    97.5
    81.3%
    94.2
    79.2%
    Month 2 after entering TFR phase
    84.9
    70.8%
    80.8
    67.9%
    Month 3 after entering TFR phase
    62.2
    51.8%
    61.5
    51.7%
    Month 4 after entering TFR phase
    51.3
    42.8%
    53.8
    45.2%
    Month 5 after entering TFR phase
    45.4
    37.8%
    46.2
    38.8%
    Month 6 after entering TFR phase
    42.9
    35.8%
    43.3
    36.4%
    Month 8 after entering TFR phase
    40.3
    33.6%
    43.3
    36.4%
    Month 10 after entering TFR phase
    38.7
    32.3%
    42.3
    35.5%
    Month 12 after entering TFR phase
    36.1
    30.1%
    39.4
    33.1%
    Month 15 after entering TFR phase
    35.3
    29.4%
    39.4
    33.1%
    Month 18 after entering TFR phase
    35.3
    29.4%
    39.4
    33.1%
    Month 21 after entering TFR phase
    34.5
    28.8%
    38.5
    32.4%
    Month 24 after entering TFR phase
    31.9
    26.6%
    35.6
    29.9%
    Month 27 after entering TFR phase
    31.9
    26.6%
    Month 30 after entering TFR phase
    31.9
    26.6%
    Month 33 after entering TFR phase
    30.3
    25.3%
    Month 36 after entering TFR phase
    23.5
    19.6%
    15. Secondary Outcome
    TitlePercentage of Participants Who Were in MR4.0 During the TFR Phase
    DescriptionNumber of participants who were in MR4.0 at selected timepoints divided by the number of participants in the TFR phase and multiplied by 100. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.0 is defined as either detectable disease ≤0.01% BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotininb 36-months treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-months treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Month 1 after entering TFR phase
    87.4
    72.8%
    83.7
    70.3%
    Month 2 after entering TFR phase
    58.0
    48.3%
    56.7
    47.6%
    Month 3 after entering TFR phase
    39.5
    32.9%
    42.3
    35.5%
    Month 4 after entering TFR phase
    36.1
    30.1%
    42.3
    35.5%
    Month 5 after entering TFR phase
    32.8
    27.3%
    41.3
    34.7%
    Month 6 after entering TFR phase
    33.6
    28%
    38.5
    32.4%
    Month 8 after entering TFR phase
    34.5
    28.8%
    40.4
    33.9%
    Month 10 after entering TFR phase
    35.3
    29.4%
    38.5
    32.4%
    Month 12 after entering TFR phase
    31.9
    26.6%
    37.5
    31.5%
    Month 15 after entering TFR phase
    34.5
    28.8%
    34.6
    29.1%
    Month 18 after entering TFR phase
    33.6
    28%
    38.5
    32.4%
    Month 21 after entering TFR phase
    30.3
    25.3%
    32.7
    27.5%
    Month 24 after entering TFR phase
    29.4
    24.5%
    30.8
    25.9%
    Month 27 after entering TFR phase
    31.1
    25.9%
    Month 30 after entering TFR phase
    30.3
    25.3%
    Month 33 after entering TFR phase
    27.7
    23.1%
    Month 36 after entering TFR phase
    26.1
    21.8%
    16. Secondary Outcome
    TitlePercentage of Participants Who Were in MR4.5 During the TFR Phase
    DescriptionNumber of participants who were in MR4.5 at selected timepoints divided by the number of participants in the TFR phase and multiplied by 100. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. Confidence intervals were calculated based on the Exact Clopper-Pearson method. MR4.5 is defined as either detectable disease ≤ 0.0032% BCR-ABL IS; or undetectable disease within cDNA with ≥ 32,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotininb 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Month 3 after entering TFR phase
    21.8
    18.2%
    26.9
    22.6%
    Month 6 after entering TFR phase
    17.6
    14.7%
    28.8
    24.2%
    Month 12 after entering TFR phase
    20.2
    16.8%
    26.9
    22.6%
    Month 15 after entering TFR phase
    18.5
    15.4%
    23.1
    19.4%
    Month 18 after entering TFR phase
    25.2
    21%
    26.9
    22.6%
    Month 21 after entering TFR phase
    22.7
    18.9%
    22.1
    18.6%
    Month 24 after entering TFR phase
    24.4
    20.3%
    20.2
    17%
    Month 27 after entering TFR phase
    21.8
    18.2%
    Month 30 after entering TFR phase
    22.7
    18.9%
    Month 33 after entering TFR phase
    19.3
    16.1%
    Month 36 after entering TFR phase
    16.8
    14%
    17. Secondary Outcome
    TitleBCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase
    DescriptionBCR-ABL transcript ratio by international scale (IS) (expressed as a percentage) during the induction/consolidation phase. Participants randomized to Nilotinib 36-month treatment arm had 12-month additional consolidation phase (post-randomization).
    Time FrameFrom baseline up to 24 months after study treatment start for Nilotinib 24-month treatment arm and Not randomized participants; and up to 36 months after study treatment start for Nilotinib 36-month treatment arm.

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure. Number analyzed signified number of participants with available data for this outcome measure at specified timepoints.
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment ArmNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants120118381
    Baseline
    0.1367
    (0.55144)
    0.0633
    (0.12790)
    0.5509
    (3.94256)
    Month 3 after study treatment start (pre-randomization)
    0.0106
    (0.02660)
    0.0086
    (0.01155)
    0.0728
    (0.22537)
    Month 6 after study treatment start (pre-randomization)
    0.0052
    (0.00631)
    0.0124
    (0.05508)
    0.0530
    (0.09587)
    Month 9 after study treatment start (pre-randomization)
    0.0049
    (0.00809)
    0.0046
    (0.00544)
    0.0573
    (0.13905)
    Month 12 after study treatment start (pre-randomization)
    0.0044
    (0.00611)
    0.0037
    (0.00440)
    0.0772
    (0.56398)
    Month 15 after study treatment start (pre-randomization)
    0.0035
    (0.00591)
    0.0034
    (0.00389)
    0.0669
    (0.37209)
    Month 18 after study treatment start (pre-randomization)
    0.0029
    (0.00354)
    0.0034
    (0.00409)
    0.0462
    (0.12284)
    Month 21 after study treatment start (pre-randomization)
    0.0028
    (0.00319)
    0.0031
    (0.00288)
    0.0390
    (0.08271)
    Month 24 after study treatment start (pre-randomization)
    0.0027
    (0.00424)
    0.0029
    (0.00319)
    0.0325
    (0.05140)
    Month 27 after study treatment start (post-randomization)
    0.0089
    (0.06119)
    Month 30 after study treatment start (post-randomization)
    0.0111
    (0.08672)
    Month 33 after study treatment start (post-randomization)
    0.0025
    (0.00439)
    Month 36 after study treatment start (post-randomization)
    0.0025
    (0.00338)
    18. Secondary Outcome
    TitleBCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase
    DescriptionBCR-ABL/control gene (ABL) transcript ratio by international scale (IS) (expressed as a percentage) during the TFR phase. BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase.
    Time FrameFrom Month 1 after entering TFR phase up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase. Number analyzed signified number of participants with available data for this outcome measure at specified timepoints.
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Month 1 after entering the TFR phase
    0.0042
    (0.00621)
    0.0074
    (0.02130)
    Month 2 after entering the TFR phase
    0.1162
    (0.35606)
    0.2122
    (0.99372)
    Month 3 after entering the TFR phase
    1.3774
    (9.71909)
    0.4754
    (1.84649)
    Month 4 after entering the TFR phase
    0.2667
    (0.80336)
    0.2506
    (0.91197)
    Month 5 after entering the TFR phase
    0.1740
    (0.76123)
    0.0801
    (0.26739)
    Month 6 after entering the TFR phase
    0.2219
    (1.51808)
    0.1095
    (0.66322)
    Month 8 after entering the TFR phase
    0.0075
    (0.01403)
    0.0042
    (0.00742)
    Month 10 after entering the TFR phase
    0.0062
    (0.01295)
    0.0039
    (0.00680)
    Month 12 after entering the TFR phase
    0.0047
    (0.00665)
    0.0027
    (0.00357)
    Month 15 after entering the TFR phase
    0.0030
    (0.00317)
    0.0043
    (0.00555)
    Month 18 after entering the TFR phase
    0.0030
    (0.00384)
    0.0027
    (0.00330)
    Month 21 after entering the TFR phase
    0.0036
    (0.00484)
    0.0041
    (0.00495)
    Month 24 after entering the TFR phase
    0.0077
    (0.02910)
    0.0047
    (0.00691)
    Month 27 after entering the TFR phase
    0.0024
    (0.00246)
    Month 30 after entering the TFR phase
    0.0023
    (0.00281)
    Month 33 after entering the TFR phase
    0.0079
    (0.02376)
    Month 36 after entering the TFR phase
    0.0041
    (0.00767)
    19. Secondary Outcome
    TitleBCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase
    DescriptionBCR-ABL/control gene (ABL) transcript ratio by international scale (IS) (expressed as a percentage) during the nilotinib re-treatment phase. BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes.
    Time FrameFrom Day 1 after entering the re-treatment phase up to 24 months after entering re-treatment phase for Nilotinib 36-month treatment arm and 36 months after entering the re-treatment phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the re-treatment phase. Number analyzed signified number of participants with available data for this outcome measure at specified timepoints.
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants7455
    Day 1 after entering the re-treatment phase
    2.8246
    (2.39596)
    0.6301
    (0.74388)
    Week 6 after entering the re-treatment phase
    0.6276
    (2.34231)
    0.3112
    (0.60279)
    Month 3 after entering the re-treatment phase
    0.0311
    (0.07265)
    0.0131
    (0.02359)
    Month 6 after entering the re-treatment phase
    0.0095
    (0.03296)
    0.0070
    (0.01330)
    Month 9 after entering the re-treatment phase
    0.0259
    (0.17766)
    0.0065
    (0.01099)
    Month 12 after entering the re-treatment phase
    0.0088
    (0.03190)
    0.0047
    (0.00839)
    Month 15 after entering the re-treatment phase
    0.0061
    (0.01322)
    0.0045
    (0.01176)
    Month 18 after entering the re-treatment phase
    0.0105
    (0.05205)
    0.0039
    (0.00581)
    Month 21 after entering the re-treatment phase
    0.0051
    (0.01699)
    0.0031
    (0.00342)
    Month 24 after entering the re-treatment phase
    0.0038
    (0.00756)
    0.0014
    (0.00197)
    Month 27 after entering the re-treatment phase
    0.0033
    (0.00439)
    Month 30 after entering the re-treatment phase
    0.0113
    (0.04446)
    Month 33 after entering the re-treatment phase
    0.0029
    (0.00541)
    Month 36 after entering the re-treatment phase
    0.0005
    (NA)
    20. Secondary Outcome
    TitleProgression-free Survival (PFS) During the TFR Phase of the Study.
    DescriptionPFS is defined as the time from the date of start of the nilotinib TFR phase to the date of acelerated phase/blast crisis (AP/BC) or death, whichever came first. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotini 24-month treatment arm had a maximum of 36 months of TFR phase. Patients not known to have recurred or died on or before the cut-off date for PFS analysis were censored at the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who were on study, and at the date of last contact for patients who were in follow-up.
    Time FrameFrom the start of the TFR phase to progression to AP/BC or death up to 24 months after entering TFR phase for Nilotininb 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Median (95% Confidence Interval) [Months]
    NA
    NA
    21. Secondary Outcome
    TitleTreatment -Free Survival (TFS) During the TFR Phase of the Study
    DescriptionTFS is defined as the time from the start of the TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4.0,re-start of nilotinib treatment, progression to AP/BC, or death from any cause. Patients not known to have had any of the events on or before the cut-off date were censored at the earlier of the date of their last assessment for patients who were still on study and the date of last contact for patients who were in follow-up. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotinib 24-month treatment arm had a maximum of 36 months of TFR phase. MMR is defined as ≥3.0 log reduction in BCR-ABL transcripts compared to the standardized baseline or ≤0.1%BCR-ABL. MR4.0 is defined as either detectable disease ≤0.01%BCR-ABL IS or undetectable disease in cDNA with ≥10,000 ABL transcripts (numbers of ABL transcripts in the same volume of cDNA used to test for BCR-ABL)
    Time FrameFrom the start of the TFR phase to the date of occurrence of treatment-free survival event, up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants119104
    Median (95% Confidence Interval) [Months]
    4.1
    4.2
    22. Secondary Outcome
    TitleOverall Survival (OS) Rate During the TFR Phase of the Study.
    DescriptionOS is defined as the time from start of the TFR phase to the time of death due to any cause. Participants randomized in Nilotinib 36-month treatment arm had a maximum of 24 months of TFR phase, whereas participants randomized in Nilotini 24-month treatment arm had a maximum of 36 months of TFR phase. For participants without any event on or before the cut-off date, survival time will be censored at the date of their last assessment for patients who are still on study, and at the date of last contact for patients who are in follow-up.
    Time FrameFrom the start of the TFR phase to death due to any cause, assessed up to 24 months after entering TFR phase for Nilotinib 36-month treatment arm and up to 36 months after entering TFR phase for Nilotinib 24-month treatment arm

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month Treatment Arm
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants120119
    Median (95% Confidence Interval) [Months]
    NA
    NA
    23. Post-Hoc Outcome
    TitleAll Collected Deaths
    DescriptionDeaths on-treatment were collected during the induction/consolidation phase (from the first dose of study drug to 30 days after study treatment discontinuation, assessed up to 24 months for Nilotinib 24-month treatment arm and Not randomized, and up to 36 months for Nilotinib 36-month treatment arm) and during the re-treatment phase (from the start date of the re-treatment phase to 30 days after study treatment discontinuation, assessed up to 36 months for Nilotinib 24-month treatment arm and up to 24 months for Nilotinib 36-month treatment arm). Total deaths were collected from first dose of study drug until end of study, up to maximum duration of 5 years
    Time FrameOn-treatment deaths: induction/consolidation phase (up to 24 months or 36 months from treatment start, depending on arm) and re-treatment phase (up to 36 months or up to 24 months from re-treatment start, depending on arm). All deaths: up to 5 years

    Outcome Measure Data

    Analysis Population Description
    All enrolled participants for whom informed consent was obtained prior to any study specific procedure were included.
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot Randomized
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.
    Measure Participants120118381
    On-treatment deaths
    1
    0.8%
    1
    0.8%
    3
    0.8%
    Total deaths
    1
    0.8%
    3
    2.5%
    10
    2.6%

    Adverse Events

    Time Frame- Induction/consolidation phase: From the first dose of study drug to 30 days after study treatment discontinuation, assessed up to 24 months for Nilotinib 24-month treatment arm and Not randomized, and up to 36 months for Nilotinib 36-month treatment arm. - Re-treatment phase: From the start date of the re-treatment phase to 30 days after study treatment discontinuation, assessed up to 36 months for Nilotinib 24-month treatment arm and up to 24 months for Nilotinib 36-month treatment arm
    Adverse Event Reporting Description Any sign or symptom that occurred during the induction/consolidation phase and re-treatment phase. For this analysis, all enrolled participants for whom informed consent was obtained prior to any study specific procedure were included.
    Arm/Group TitleNilotinib 24-month TreatmentNilotinib 36-month TreatmentNot RandomizedTotal
    Arm/Group DescriptionParticipants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phaseParticipants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phaseParticipants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.Total
    All Cause Mortality
    Nilotinib 24-month TreatmentNilotinib 36-month TreatmentNot RandomizedTotal
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/120 (0.8%) 1/118 (0.8%) 3/381 (0.8%) 5/619 (0.8%)
    Serious Adverse Events
    Nilotinib 24-month TreatmentNilotinib 36-month TreatmentNot RandomizedTotal
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total33/120 (27.5%) 27/118 (22.9%) 76/381 (19.9%) 136/619 (22%)
    Blood and lymphatic system disorders
    Febrile neutropenia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lymphadenopathy mediastinal0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Cardiac disorders
    Acute coronary syndrome2/120 (1.7%) 0/118 (0%) 1/381 (0.3%) 3/619 (0.5%)
    Acute myocardial infarction0/120 (0%) 1/118 (0.8%) 2/381 (0.5%) 3/619 (0.5%)
    Angina pectoris0/120 (0%) 0/118 (0%) 5/381 (1.3%) 5/619 (0.8%)
    Angina unstable1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Arrhythmia supraventricular0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Atrial fibrillation3/120 (2.5%) 2/118 (1.7%) 4/381 (1%) 9/619 (1.5%)
    Atrial flutter0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cardiac failure0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Cardiac failure acute0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cardiac failure congestive0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Coronary artery disease0/120 (0%) 0/118 (0%) 4/381 (1%) 4/619 (0.6%)
    Coronary artery stenosis0/120 (0%) 0/118 (0%) 3/381 (0.8%) 3/619 (0.5%)
    Hypertensive cardiomyopathy0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Myocardial infarction2/120 (1.7%) 0/118 (0%) 4/381 (1%) 6/619 (1%)
    Myocardial ischaemia1/120 (0.8%) 0/118 (0%) 2/381 (0.5%) 3/619 (0.5%)
    Myocarditis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Sinus bradycardia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Tachyarrhythmia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ventricular arrhythmia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ear and labyrinth disorders
    Vertigo0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Eye disorders
    Retinal detachment1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gastrointestinal disorders
    Abdominal pain upper0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Anal fissure0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Anal fistula0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Constipation0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Duodenal ulcer1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gastritis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Gastrooesophageal reflux disease1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Haematochezia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Haemorrhoids0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Inguinal hernia1/120 (0.8%) 1/118 (0.8%) 0/381 (0%) 2/619 (0.3%)
    Intestinal obstruction0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lumbar hernia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Nausea0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Pancreatitis0/120 (0%) 0/118 (0%) 3/381 (0.8%) 3/619 (0.5%)
    Pancreatitis acute0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Umbilical hernia0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Vomiting0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    General disorders
    Death1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    General physical health deterioration0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Hyperplasia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Multiple organ dysfunction syndrome0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Necrosis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Pyrexia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Sudden death0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Hepatobiliary disorders
    Cholangitis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cholecystitis0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Cholecystitis acute1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Cholelithiasis0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Immune system disorders
    Sarcoidosis0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Infections and infestations
    Anal abscess0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Bacterial pyelonephritis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Bronchitis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cellulitis1/120 (0.8%) 2/118 (1.7%) 0/381 (0%) 3/619 (0.5%)
    Cystitis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Enterocolitis infectious1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gallbladder empyema1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gangrene0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Influenza0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Laryngitis0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Lower respiratory tract infection0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Neuroborreliosis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Orchitis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Pneumonia0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Pneumonia legionella1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Pneumonia streptococcal1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Sepsis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Urinary tract infection0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Vestibular neuronitis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Injury, poisoning and procedural complications
    Eye contusion1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Femoral neck fracture0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Humerus fracture0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Injury0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Limb injury0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lower limb fracture1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Overdose0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Tendon rupture1/120 (0.8%) 0/118 (0%) 1/381 (0.3%) 2/619 (0.3%)
    Investigations
    Amylase increased1/120 (0.8%) 0/118 (0%) 1/381 (0.3%) 2/619 (0.3%)
    Electrocardiogram abnormal0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lipase increased0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Troponin increased1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Metabolism and nutrition disorders
    Diabetes mellitus0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Diabetes mellitus inadequate control0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hyperkalaemia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Hyponatraemia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Musculoskeletal and connective tissue disorders
    Arthropathy0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Back pain0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Bursitis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Intervertebral disc disorder0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Intervertebral disc protrusion1/120 (0.8%) 0/118 (0%) 2/381 (0.5%) 3/619 (0.5%)
    Metatarsalgia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Musculoskeletal pain0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Osteoarthritis2/120 (1.7%) 0/118 (0%) 0/381 (0%) 2/619 (0.3%)
    Pain in extremity0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Spinal stenosis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Spondylitis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Glioblastoma0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Lung adenocarcinoma0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Myelofibrosis0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Non-Hodgkin's lymphoma0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ovarian cancer0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Nervous system disorders
    Cerebral artery thrombosis1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Cerebral infarction1/120 (0.8%) 0/118 (0%) 1/381 (0.3%) 2/619 (0.3%)
    Cerebral ischaemia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Cerebrovascular accident1/120 (0.8%) 0/118 (0%) 3/381 (0.8%) 4/619 (0.6%)
    Dizziness2/120 (1.7%) 0/118 (0%) 0/381 (0%) 2/619 (0.3%)
    Epilepsy0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Facial paralysis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Headache0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hypoaesthesia0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Ischaemic stroke0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Mononeuropathy0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Seizure1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Syncope1/120 (0.8%) 1/118 (0.8%) 2/381 (0.5%) 4/619 (0.6%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Psychiatric disorders
    Adjustment disorder0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Mental disorder0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Renal and urinary disorders
    Haematuria0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Renal failure0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Urinary retention0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Reproductive system and breast disorders
    Acquired hydrocele0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Adnexa uteri mass1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Menorrhagia0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ovarian cyst0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Dyspnoea0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Pleural effusion0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Pulmonary embolism0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Respiratory failure1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Skin and subcutaneous tissue disorders
    Alopecia0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hyperhidrosis0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hyperkeratosis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Vascular disorders
    Arterial disorder0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Arterial occlusive disease0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Extremity necrosis0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Haematoma1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Hypertensive crisis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Intermittent claudication0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ischaemia1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Peripheral arterial occlusive disease0/120 (0%) 1/118 (0.8%) 2/381 (0.5%) 3/619 (0.5%)
    Peripheral artery occlusion1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Peripheral artery stenosis0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Peripheral ischaemia1/120 (0.8%) 1/118 (0.8%) 0/381 (0%) 2/619 (0.3%)
    Thromboangiitis obliterans0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Other (Not Including Serious) Adverse Events
    Nilotinib 24-month TreatmentNilotinib 36-month TreatmentNot RandomizedTotal
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total97/120 (80.8%) 104/118 (88.1%) 280/381 (73.5%) 481/619 (77.7%)
    Gastrointestinal disorders
    Abdominal pain7/120 (5.8%) 6/118 (5.1%) 15/381 (3.9%) 28/619 (4.5%)
    Abdominal pain upper12/120 (10%) 14/118 (11.9%) 19/381 (5%) 45/619 (7.3%)
    Constipation19/120 (15.8%) 14/118 (11.9%) 25/381 (6.6%) 58/619 (9.4%)
    Diarrhoea6/120 (5%) 5/118 (4.2%) 11/381 (2.9%) 22/619 (3.6%)
    Dyspepsia4/120 (3.3%) 7/118 (5.9%) 6/381 (1.6%) 17/619 (2.7%)
    Nausea13/120 (10.8%) 5/118 (4.2%) 11/381 (2.9%) 29/619 (4.7%)
    Vomiting10/120 (8.3%) 3/118 (2.5%) 9/381 (2.4%) 22/619 (3.6%)
    General disorders
    Asthenia16/120 (13.3%) 14/118 (11.9%) 27/381 (7.1%) 57/619 (9.2%)
    Fatigue13/120 (10.8%) 7/118 (5.9%) 17/381 (4.5%) 37/619 (6%)
    Influenza like illness2/120 (1.7%) 6/118 (5.1%) 2/381 (0.5%) 10/619 (1.6%)
    Pyrexia5/120 (4.2%) 10/118 (8.5%) 23/381 (6%) 38/619 (6.1%)
    Infections and infestations
    Bronchitis8/120 (6.7%) 9/118 (7.6%) 14/381 (3.7%) 31/619 (5%)
    Folliculitis6/120 (5%) 4/118 (3.4%) 4/381 (1%) 14/619 (2.3%)
    Gastroenteritis10/120 (8.3%) 3/118 (2.5%) 4/381 (1%) 17/619 (2.7%)
    Influenza6/120 (5%) 9/118 (7.6%) 15/381 (3.9%) 30/619 (4.8%)
    Nasopharyngitis4/120 (3.3%) 12/118 (10.2%) 14/381 (3.7%) 30/619 (4.8%)
    Upper respiratory tract infection8/120 (6.7%) 8/118 (6.8%) 11/381 (2.9%) 27/619 (4.4%)
    Investigations
    Alanine aminotransferase increased10/120 (8.3%) 18/118 (15.3%) 27/381 (7.1%) 55/619 (8.9%)
    Aspartate aminotransferase increased8/120 (6.7%) 12/118 (10.2%) 11/381 (2.9%) 31/619 (5%)
    Blood bilirubin increased8/120 (6.7%) 13/118 (11%) 30/381 (7.9%) 51/619 (8.2%)
    Blood cholesterol increased15/120 (12.5%) 14/118 (11.9%) 24/381 (6.3%) 53/619 (8.6%)
    Blood triglycerides increased3/120 (2.5%) 8/118 (6.8%) 6/381 (1.6%) 17/619 (2.7%)
    Gamma-glutamyltransferase increased4/120 (3.3%) 6/118 (5.1%) 9/381 (2.4%) 19/619 (3.1%)
    Lipase increased21/120 (17.5%) 10/118 (8.5%) 34/381 (8.9%) 65/619 (10.5%)
    Weight increased5/120 (4.2%) 6/118 (5.1%) 3/381 (0.8%) 14/619 (2.3%)
    Metabolism and nutrition disorders
    Decreased appetite6/120 (5%) 1/118 (0.8%) 5/381 (1.3%) 12/619 (1.9%)
    Dyslipidaemia0/120 (0%) 7/118 (5.9%) 5/381 (1.3%) 12/619 (1.9%)
    Hypercholesterolaemia23/120 (19.2%) 20/118 (16.9%) 65/381 (17.1%) 108/619 (17.4%)
    Hyperglycaemia5/120 (4.2%) 16/118 (13.6%) 16/381 (4.2%) 37/619 (6%)
    Hypertriglyceridaemia10/120 (8.3%) 2/118 (1.7%) 14/381 (3.7%) 26/619 (4.2%)
    Hypophosphataemia7/120 (5.8%) 13/118 (11%) 13/381 (3.4%) 33/619 (5.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia17/120 (14.2%) 18/118 (15.3%) 27/381 (7.1%) 62/619 (10%)
    Back pain16/120 (13.3%) 11/118 (9.3%) 21/381 (5.5%) 48/619 (7.8%)
    Muscle spasms10/120 (8.3%) 16/118 (13.6%) 12/381 (3.1%) 38/619 (6.1%)
    Musculoskeletal pain4/120 (3.3%) 11/118 (9.3%) 6/381 (1.6%) 21/619 (3.4%)
    Myalgia12/120 (10%) 15/118 (12.7%) 26/381 (6.8%) 53/619 (8.6%)
    Pain in extremity12/120 (10%) 21/118 (17.8%) 26/381 (6.8%) 59/619 (9.5%)
    Nervous system disorders
    Headache17/120 (14.2%) 12/118 (10.2%) 34/381 (8.9%) 63/619 (10.2%)
    Paraesthesia6/120 (5%) 4/118 (3.4%) 9/381 (2.4%) 19/619 (3.1%)
    Sciatica5/120 (4.2%) 7/118 (5.9%) 9/381 (2.4%) 21/619 (3.4%)
    Psychiatric disorders
    Insomnia4/120 (3.3%) 6/118 (5.1%) 3/381 (0.8%) 13/619 (2.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough9/120 (7.5%) 15/118 (12.7%) 13/381 (3.4%) 37/619 (6%)
    Skin and subcutaneous tissue disorders
    Alopecia6/120 (5%) 9/118 (7.6%) 18/381 (4.7%) 33/619 (5.3%)
    Dry skin9/120 (7.5%) 15/118 (12.7%) 17/381 (4.5%) 41/619 (6.6%)
    Pruritus15/120 (12.5%) 23/118 (19.5%) 57/381 (15%) 95/619 (15.3%)
    Rash21/120 (17.5%) 10/118 (8.5%) 41/381 (10.8%) 72/619 (11.6%)
    Vascular disorders
    Hypertension20/120 (16.7%) 25/118 (21.2%) 27/381 (7.1%) 72/619 (11.6%)

    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
    Phone862-778-8300
    Emailnovartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01743989
    Other Study ID Numbers:
    • CAMN107AIC05
    • 2012-005124-15
    First Posted:
    Dec 6, 2012
    Last Update Posted:
    Jul 15, 2021
    Last Verified:
    Jun 1, 2021