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
208
3
86.8
3
0

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

Arm Intervention/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

    Site City State Country Postal Code
    1 Novartis Investigative Site Linz Oberoesterreich Austria A 4020
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    146 Novartis Investigative Site Warszawa Poland 02 776
    147 Novartis Investigative Site Lisboa Portugal 1099 023
    148 Novartis Investigative Site Lisboa Portugal 1749-035
    149 Novartis Investigative Site Porto Portugal 4099-001
    150 Novartis Investigative Site Porto Portugal 4200 319
    151 Novartis Investigative Site Porto Portugal 4200-072
    152 Novartis Investigative Site Bucharest District 2 Romania 022328
    153 Novartis Investigative Site Bucharest Romania 030 171
    154 Novartis Investigative Site Bucharest Romania 500098
    155 Novartis Investigative Site Cluj-Napoca Romania 400124
    156 Novartis Investigative Site Iasi Romania 700483
    157 Novartis Investigative Site Sibiu Romania 550245
    158 Novartis Investigative Site Timisoara Romania 300 079
    159 Novartis Investigative Site Belgrade Serbia 11000
    160 Novartis Investigative Site Belgrade Serbia 11070
    161 Novartis Investigative Site Nis Serbia 18000
    162 Novartis Investigative Site Novi Sad Serbia
    163 Novartis Investigative Site Bratislava Slovakia 85107
    164 Novartis Investigative Site Martin Slovakia 03601
    165 Novartis Investigative Site Ljubljana Slovenia 1000
    166 Novartis Investigative Site Granada Andalucia Spain 18014
    167 Novartis Investigative Site Jaen Andalucia Spain 23007
    168 Novartis Investigative Site Malaga Andalucia Spain 29010
    169 Novartis Investigative Site Sevilla Andalucia Spain 41009
    170 Novartis Investigative Site Sevilla Andalucia Spain 41013
    171 Novartis Investigative Site Sabadell Barcelona Spain 08208
    172 Novartis Investigative Site León Castilla Y Leon Spain 24071
    173 Novartis Investigative Site Salamanca Castilla Y Leon Spain 37007
    174 Novartis Investigative Site Valladolid Castilla Y Leon Spain 47011
    175 Novartis Investigative Site Badalona Catalunya Spain 08916
    176 Novartis Investigative Site Barcelona Catalunya Spain 08003
    177 Novartis Investigative Site Barcelona Catalunya Spain 08035
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    179 Novartis Investigative Site Girona Catalunya Spain 17007
    180 Novartis Investigative Site Hospitalet de LLobregat Catalunya Spain 08907
    181 Novartis Investigative Site Tarragona Catalunya Spain 43005
    182 Novartis Investigative Site Alicante Comunidad Valenciana Spain 03010
    183 Novartis Investigative Site Alzira Comunidad Valenciana Spain 46600
    184 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46026
    185 Novartis Investigative Site Caceres Extremadura Spain 10003
    186 Novartis Investigative Site La Coruna Galicia Spain 15006
    187 Novartis Investigative Site Pontevedra Galicia Spain 36071
    188 Novartis Investigative Site Santiago de Compostela Galicia Spain 15706
    189 Novartis Investigative Site Palma De Mallorca Islas Baleares Spain 07120
    190 Novartis Investigative Site Pamplona Navarra Spain 31008
    191 Novartis Investigative Site San Sebastian Pais Vasco Spain 20080
    192 Novartis Investigative Site Granollers Spain 08402
    193 Novartis Investigative Site Madrid Spain 28006
    194 Novartis Investigative Site Madrid Spain 28009
    195 Novartis Investigative Site Madrid Spain 28031
    196 Novartis Investigative Site Madrid Spain 28034
    197 Novartis Investigative Site Madrid Spain 28040
    198 Novartis Investigative Site Madrid Spain 28041
    199 Novartis Investigative Site Madrid Spain 28046
    200 Novartis Investigative Site Madrid Spain 28222
    201 Novartis Investigative Site Murcia Spain 30008
    202 Novartis Investigative Site Santa Cruz de Tenerife Spain 38009
    203 Novartis Investigative Site Zaragoza Spain 50009
    204 Novartis Investigative Site Stockholm Sweden SE-171 76
    205 Novartis Investigative Site East Yorkshire United Kingdom HU16 5JQ
    206 Novartis Investigative Site Edinburgh United Kingdom EH4 2XU
    207 Novartis Investigative Site London United Kingdom EC1A 7BE
    208 Novartis Investigative Site London United Kingdom W12 0HS

    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 Detail For 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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
    STARTED 120 119 381
    Participants Who Signed Informed Consent 120 118 381
    COMPLETED 119 104 0
    NOT COMPLETED 1 15 381
    Period Title: Treatment Phase
    STARTED 119 104 0
    COMPLETED 37 36 0
    NOT COMPLETED 82 68 0
    Period Title: Treatment Phase
    STARTED 74 55 0
    COMPLETED 58 46 0
    NOT COMPLETED 16 9 0

    Baseline Characteristics

    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized Total
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 120 119 381 620
    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
    Title Percentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase
    Description 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
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    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 Hypothesis p-Value 0.383
    Comments
    Method Chi-squared
    Comments
    2. Secondary Outcome
    Title Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
    Description 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.
    Time Frame From 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 23 16 98
    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
    Title Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
    Description 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.
    Time Frame From 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 Title Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 16
    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
    Title Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
    Description 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)
    Time Frame From 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 92 94 357
    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
    Title Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
    Description 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)
    Time Frame From 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 Title Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 94
    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
    Title Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
    Description 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)
    Time Frame From 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 109 109 374
    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
    Title Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
    Description 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)
    Time Frame From 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 Title Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 109
    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
    Title Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase
    Description 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.
    Time Frame From 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 120 118 381
    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
    Title Cumulative Incidence of MMR During the Post-randomization Consolidation Phase
    Description 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.
    Time Frame From 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 Title Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 118
    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
    Title Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase
    Description 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)
    Time Frame From 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 120 118 381
    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
    Title Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase
    Description 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)
    Time Frame From 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 Title Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 118
    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
    Title Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase
    Description 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)
    Time Frame From 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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 120 118 381
    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
    Title Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase
    Description 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)
    Time Frame From 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 Title Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 118
    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
    Title Percentage of Participants Who Were in MMR During TFR Phase
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    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
    Title Percentage of Participants Who Were in MR4.0 During the TFR Phase
    Description 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)
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    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
    Title Percentage of Participants Who Were in MR4.5 During the TFR Phase
    Description 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)
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    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
    Title BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase
    Description 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).
    Time Frame 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.

    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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 120 118 381
    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
    Title BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase
    Description 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.
    Time Frame 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

    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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    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
    Title BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase
    Description 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.
    Time Frame 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

    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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 74 55
    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
    Title Progression-free Survival (PFS) During the TFR Phase of the Study.
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    Median (95% Confidence Interval) [Months]
    NA
    NA
    21. Secondary Outcome
    Title Treatment -Free Survival (TFS) During the TFR Phase of the Study
    Description 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)
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects who entered the TFR phase
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 119 104
    Median (95% Confidence Interval) [Months]
    4.1
    4.2
    22. Secondary Outcome
    Title Overall Survival (OS) Rate During the TFR Phase of the Study.
    Description 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.
    Time Frame 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

    Outcome Measure Data

    Analysis Population Description
    All enrolled subjects
    Arm/Group Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Arm
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase
    Measure Participants 120 119
    Median (95% Confidence Interval) [Months]
    NA
    NA
    23. Post-Hoc Outcome
    Title All Collected Deaths
    Description Deaths 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 Frame On-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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Participants 120 118 381
    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 Title Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized Total
    Arm/Group Description Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase Participants 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 Treatment Nilotinib 36-month Treatment Not Randomized Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/120 (0.8%) 1/118 (0.8%) 3/381 (0.8%) 5/619 (0.8%)
    Serious Adverse Events
    Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 33/120 (27.5%) 27/118 (22.9%) 76/381 (19.9%) 136/619 (22%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lymphadenopathy mediastinal 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Cardiac disorders
    Acute coronary syndrome 2/120 (1.7%) 0/118 (0%) 1/381 (0.3%) 3/619 (0.5%)
    Acute myocardial infarction 0/120 (0%) 1/118 (0.8%) 2/381 (0.5%) 3/619 (0.5%)
    Angina pectoris 0/120 (0%) 0/118 (0%) 5/381 (1.3%) 5/619 (0.8%)
    Angina unstable 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Arrhythmia supraventricular 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Atrial fibrillation 3/120 (2.5%) 2/118 (1.7%) 4/381 (1%) 9/619 (1.5%)
    Atrial flutter 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cardiac failure 0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Cardiac failure acute 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cardiac failure congestive 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Coronary artery disease 0/120 (0%) 0/118 (0%) 4/381 (1%) 4/619 (0.6%)
    Coronary artery stenosis 0/120 (0%) 0/118 (0%) 3/381 (0.8%) 3/619 (0.5%)
    Hypertensive cardiomyopathy 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Myocardial infarction 2/120 (1.7%) 0/118 (0%) 4/381 (1%) 6/619 (1%)
    Myocardial ischaemia 1/120 (0.8%) 0/118 (0%) 2/381 (0.5%) 3/619 (0.5%)
    Myocarditis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Sinus bradycardia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Tachyarrhythmia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ventricular arrhythmia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ear and labyrinth disorders
    Vertigo 0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Eye disorders
    Retinal detachment 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gastrointestinal disorders
    Abdominal pain upper 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Anal fissure 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Anal fistula 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Constipation 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Duodenal ulcer 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gastritis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Gastrooesophageal reflux disease 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Haematochezia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Haemorrhoids 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Inguinal hernia 1/120 (0.8%) 1/118 (0.8%) 0/381 (0%) 2/619 (0.3%)
    Intestinal obstruction 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lumbar hernia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Nausea 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Pancreatitis 0/120 (0%) 0/118 (0%) 3/381 (0.8%) 3/619 (0.5%)
    Pancreatitis acute 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Umbilical hernia 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Vomiting 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    General disorders
    Death 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    General physical health deterioration 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Hyperplasia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Multiple organ dysfunction syndrome 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Necrosis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Pyrexia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Sudden death 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Hepatobiliary disorders
    Cholangitis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cholecystitis 0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Cholecystitis acute 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Cholelithiasis 0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Immune system disorders
    Sarcoidosis 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Infections and infestations
    Anal abscess 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Bacterial pyelonephritis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Bronchitis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Cellulitis 1/120 (0.8%) 2/118 (1.7%) 0/381 (0%) 3/619 (0.5%)
    Cystitis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Enterocolitis infectious 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gallbladder empyema 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Gangrene 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Influenza 0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Laryngitis 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Lower respiratory tract infection 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Neuroborreliosis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Orchitis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Pneumonia 0/120 (0%) 1/118 (0.8%) 1/381 (0.3%) 2/619 (0.3%)
    Pneumonia legionella 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Pneumonia streptococcal 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Sepsis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Urinary tract infection 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Vestibular neuronitis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Injury, poisoning and procedural complications
    Eye contusion 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Femoral neck fracture 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Humerus fracture 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Injury 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Limb injury 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lower limb fracture 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Overdose 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Tendon rupture 1/120 (0.8%) 0/118 (0%) 1/381 (0.3%) 2/619 (0.3%)
    Investigations
    Amylase increased 1/120 (0.8%) 0/118 (0%) 1/381 (0.3%) 2/619 (0.3%)
    Electrocardiogram abnormal 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Lipase increased 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Troponin increased 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Metabolism and nutrition disorders
    Diabetes mellitus 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Diabetes mellitus inadequate control 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hyperkalaemia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Hyponatraemia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Musculoskeletal and connective tissue disorders
    Arthropathy 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Back pain 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Bursitis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Intervertebral disc disorder 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Intervertebral disc protrusion 1/120 (0.8%) 0/118 (0%) 2/381 (0.5%) 3/619 (0.5%)
    Metatarsalgia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Musculoskeletal pain 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Osteoarthritis 2/120 (1.7%) 0/118 (0%) 0/381 (0%) 2/619 (0.3%)
    Pain in extremity 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Spinal stenosis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Spondylitis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Glioblastoma 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Lung adenocarcinoma 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Myelofibrosis 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Non-Hodgkin's lymphoma 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ovarian cancer 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Nervous system disorders
    Cerebral artery thrombosis 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Cerebral infarction 1/120 (0.8%) 0/118 (0%) 1/381 (0.3%) 2/619 (0.3%)
    Cerebral ischaemia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Cerebrovascular accident 1/120 (0.8%) 0/118 (0%) 3/381 (0.8%) 4/619 (0.6%)
    Dizziness 2/120 (1.7%) 0/118 (0%) 0/381 (0%) 2/619 (0.3%)
    Epilepsy 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Facial paralysis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Headache 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hypoaesthesia 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Ischaemic stroke 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Mononeuropathy 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Seizure 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Syncope 1/120 (0.8%) 1/118 (0.8%) 2/381 (0.5%) 4/619 (0.6%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Psychiatric disorders
    Adjustment disorder 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Mental disorder 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Renal and urinary disorders
    Haematuria 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Renal failure 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Urinary retention 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Reproductive system and breast disorders
    Acquired hydrocele 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Adnexa uteri mass 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Menorrhagia 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ovarian cyst 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Dyspnoea 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Pleural effusion 0/120 (0%) 0/118 (0%) 2/381 (0.5%) 2/619 (0.3%)
    Pulmonary embolism 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Respiratory failure 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hyperhidrosis 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Hyperkeratosis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Vascular disorders
    Arterial disorder 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Arterial occlusive disease 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Extremity necrosis 0/120 (0%) 1/118 (0.8%) 0/381 (0%) 1/619 (0.2%)
    Haematoma 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Hypertensive crisis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Intermittent claudication 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Ischaemia 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Peripheral arterial occlusive disease 0/120 (0%) 1/118 (0.8%) 2/381 (0.5%) 3/619 (0.5%)
    Peripheral artery occlusion 1/120 (0.8%) 0/118 (0%) 0/381 (0%) 1/619 (0.2%)
    Peripheral artery stenosis 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Peripheral ischaemia 1/120 (0.8%) 1/118 (0.8%) 0/381 (0%) 2/619 (0.3%)
    Thromboangiitis obliterans 0/120 (0%) 0/118 (0%) 1/381 (0.3%) 1/619 (0.2%)
    Other (Not Including Serious) Adverse Events
    Nilotinib 24-month Treatment Nilotinib 36-month Treatment Not Randomized Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 97/120 (80.8%) 104/118 (88.1%) 280/381 (73.5%) 481/619 (77.7%)
    Gastrointestinal disorders
    Abdominal pain 7/120 (5.8%) 6/118 (5.1%) 15/381 (3.9%) 28/619 (4.5%)
    Abdominal pain upper 12/120 (10%) 14/118 (11.9%) 19/381 (5%) 45/619 (7.3%)
    Constipation 19/120 (15.8%) 14/118 (11.9%) 25/381 (6.6%) 58/619 (9.4%)
    Diarrhoea 6/120 (5%) 5/118 (4.2%) 11/381 (2.9%) 22/619 (3.6%)
    Dyspepsia 4/120 (3.3%) 7/118 (5.9%) 6/381 (1.6%) 17/619 (2.7%)
    Nausea 13/120 (10.8%) 5/118 (4.2%) 11/381 (2.9%) 29/619 (4.7%)
    Vomiting 10/120 (8.3%) 3/118 (2.5%) 9/381 (2.4%) 22/619 (3.6%)
    General disorders
    Asthenia 16/120 (13.3%) 14/118 (11.9%) 27/381 (7.1%) 57/619 (9.2%)
    Fatigue 13/120 (10.8%) 7/118 (5.9%) 17/381 (4.5%) 37/619 (6%)
    Influenza like illness 2/120 (1.7%) 6/118 (5.1%) 2/381 (0.5%) 10/619 (1.6%)
    Pyrexia 5/120 (4.2%) 10/118 (8.5%) 23/381 (6%) 38/619 (6.1%)
    Infections and infestations
    Bronchitis 8/120 (6.7%) 9/118 (7.6%) 14/381 (3.7%) 31/619 (5%)
    Folliculitis 6/120 (5%) 4/118 (3.4%) 4/381 (1%) 14/619 (2.3%)
    Gastroenteritis 10/120 (8.3%) 3/118 (2.5%) 4/381 (1%) 17/619 (2.7%)
    Influenza 6/120 (5%) 9/118 (7.6%) 15/381 (3.9%) 30/619 (4.8%)
    Nasopharyngitis 4/120 (3.3%) 12/118 (10.2%) 14/381 (3.7%) 30/619 (4.8%)
    Upper respiratory tract infection 8/120 (6.7%) 8/118 (6.8%) 11/381 (2.9%) 27/619 (4.4%)
    Investigations
    Alanine aminotransferase increased 10/120 (8.3%) 18/118 (15.3%) 27/381 (7.1%) 55/619 (8.9%)
    Aspartate aminotransferase increased 8/120 (6.7%) 12/118 (10.2%) 11/381 (2.9%) 31/619 (5%)
    Blood bilirubin increased 8/120 (6.7%) 13/118 (11%) 30/381 (7.9%) 51/619 (8.2%)
    Blood cholesterol increased 15/120 (12.5%) 14/118 (11.9%) 24/381 (6.3%) 53/619 (8.6%)
    Blood triglycerides increased 3/120 (2.5%) 8/118 (6.8%) 6/381 (1.6%) 17/619 (2.7%)
    Gamma-glutamyltransferase increased 4/120 (3.3%) 6/118 (5.1%) 9/381 (2.4%) 19/619 (3.1%)
    Lipase increased 21/120 (17.5%) 10/118 (8.5%) 34/381 (8.9%) 65/619 (10.5%)
    Weight increased 5/120 (4.2%) 6/118 (5.1%) 3/381 (0.8%) 14/619 (2.3%)
    Metabolism and nutrition disorders
    Decreased appetite 6/120 (5%) 1/118 (0.8%) 5/381 (1.3%) 12/619 (1.9%)
    Dyslipidaemia 0/120 (0%) 7/118 (5.9%) 5/381 (1.3%) 12/619 (1.9%)
    Hypercholesterolaemia 23/120 (19.2%) 20/118 (16.9%) 65/381 (17.1%) 108/619 (17.4%)
    Hyperglycaemia 5/120 (4.2%) 16/118 (13.6%) 16/381 (4.2%) 37/619 (6%)
    Hypertriglyceridaemia 10/120 (8.3%) 2/118 (1.7%) 14/381 (3.7%) 26/619 (4.2%)
    Hypophosphataemia 7/120 (5.8%) 13/118 (11%) 13/381 (3.4%) 33/619 (5.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 17/120 (14.2%) 18/118 (15.3%) 27/381 (7.1%) 62/619 (10%)
    Back pain 16/120 (13.3%) 11/118 (9.3%) 21/381 (5.5%) 48/619 (7.8%)
    Muscle spasms 10/120 (8.3%) 16/118 (13.6%) 12/381 (3.1%) 38/619 (6.1%)
    Musculoskeletal pain 4/120 (3.3%) 11/118 (9.3%) 6/381 (1.6%) 21/619 (3.4%)
    Myalgia 12/120 (10%) 15/118 (12.7%) 26/381 (6.8%) 53/619 (8.6%)
    Pain in extremity 12/120 (10%) 21/118 (17.8%) 26/381 (6.8%) 59/619 (9.5%)
    Nervous system disorders
    Headache 17/120 (14.2%) 12/118 (10.2%) 34/381 (8.9%) 63/619 (10.2%)
    Paraesthesia 6/120 (5%) 4/118 (3.4%) 9/381 (2.4%) 19/619 (3.1%)
    Sciatica 5/120 (4.2%) 7/118 (5.9%) 9/381 (2.4%) 21/619 (3.4%)
    Psychiatric disorders
    Insomnia 4/120 (3.3%) 6/118 (5.1%) 3/381 (0.8%) 13/619 (2.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 9/120 (7.5%) 15/118 (12.7%) 13/381 (3.4%) 37/619 (6%)
    Skin and subcutaneous tissue disorders
    Alopecia 6/120 (5%) 9/118 (7.6%) 18/381 (4.7%) 33/619 (5.3%)
    Dry skin 9/120 (7.5%) 15/118 (12.7%) 17/381 (4.5%) 41/619 (6.6%)
    Pruritus 15/120 (12.5%) 23/118 (19.5%) 57/381 (15%) 95/619 (15.3%)
    Rash 21/120 (17.5%) 10/118 (8.5%) 41/381 (10.8%) 72/619 (11.6%)
    Vascular disorders
    Hypertension 20/120 (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/Title Study director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email novartis.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