ENESTPath: A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML.
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
This was a prospective, randomized, open-label, multicenter Phase III study. The study design was made up of 3 phases:
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Nilotinib induction phase: 12 months
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Nilotinib consolidation phase: 12 or 24 months, depending on randomization
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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:
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suspend nilotinib treatment immediately and enter the TFR phase for 36 months (Nilotinib 24-month treatment arm), or
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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:
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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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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)
- 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)
- 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)
- 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)
- 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.
- 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.
- 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)
- 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)
- 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)
- 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)
- 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.
- 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)
- 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)
- 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).
- 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.
- 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.
- 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.
- 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)
- 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
Key Inclusion Criteria:
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Confirmed diagnosis of chronic phase Ph+ CML
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Previous first-line treatment with imatinib for a minimum of 2 years;
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Patient in complete cytogenetic response;
Key Exclusion Criteria:
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Previous achievement of MR4.0 at study entry;
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Previous treatment with other target cells inhibitors other than imatinib;
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Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;
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Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;
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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;
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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;
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Patients who have not recovered from prior surgery;
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Treatment with other investigational agents within 4 weeks of Day 1;
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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 | |
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1 | Novartis Investigative Site | Linz | Oberoesterreich | Austria | A 4020 |
2 | Novartis Investigative Site | Graz | Austria | 8036 | |
3 | Novartis Investigative Site | Linz | Austria | 4010 | |
4 | Novartis Investigative Site | Linz | Austria | A-4010 | |
5 | Novartis Investigative Site | Rankweil | Austria | A-6830 | |
6 | Novartis Investigative Site | Salzburg | Austria | 5020 | |
7 | Novartis Investigative Site | Bruxelles | Belgium | 1070 | |
8 | Novartis Investigative Site | Liege | Belgium | 4000 | |
9 | Novartis Investigative Site | Pleven | Bulgaria | 5800 | |
10 | Novartis Investigative Site | Plovdiv | Bulgaria | 4002 | |
11 | Novartis Investigative Site | Sofia | Bulgaria | 1431 | |
12 | Novartis Investigative Site | Sofia | Bulgaria | 1756 | |
13 | Novartis Investigative Site | Varna | Bulgaria | 9000 | |
14 | Novartis Investigative Site | Brno Bohunice | Czech Republic | Czechia | 625 00 |
15 | Novartis Investigative Site | Hradec Kralove | CZE | Czechia | 500 05 |
16 | Novartis Investigative Site | Holstebro | Denmark | DK-7500 | |
17 | Novartis Investigative Site | Roskilde | Denmark | 4000 | |
18 | Novartis Investigative Site | HUS Helsinki | Finland | FIN-00029 | |
19 | Novartis Investigative Site | Bayonne | Bayonne Cedex | France | 64109 |
20 | Novartis Investigative Site | Le Mans | Cedex 09 | France | 72037 |
21 | Novartis Investigative Site | Paris Cedex 10 | Cedex 10 | France | 75475 |
22 | Novartis Investigative Site | Caen | Cedex | France | 14033 |
23 | Novartis Investigative Site | Angers Cedex 1 | France | 49033 | |
24 | Novartis Investigative Site | Bordeaux Cedex | France | 33000 | |
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26 | Novartis Investigative Site | Chalon sur Saône | France | 71321 | |
27 | Novartis Investigative Site | Chambéry cedex | France | 73011 | |
28 | Novartis Investigative Site | Clermont Ferrand cedex 1 | France | 63003 | |
29 | Novartis Investigative Site | Corbeil Essonnes | France | 91100 | |
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37 | Novartis Investigative Site | Metz | France | 57000 | |
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50 | Novartis Investigative Site | Berlin | Germany | 13353 | |
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54 | Novartis Investigative Site | Dresden | Germany | 01307 | |
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56 | Novartis Investigative Site | Frankfurt | Germany | 60596 | |
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80 | Novartis Investigative Site | Athens | GR | Greece | 115 27 |
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82 | Novartis Investigative Site | Athens | Greece | 106 76 | |
83 | Novartis Investigative Site | Athens | Greece | 115 27 | |
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107 | Novartis Investigative Site | Milano | MI | Italy | 20162 |
108 | Novartis Investigative Site | Modena | MO | Italy | 41124 |
109 | Novartis Investigative Site | Palermo | PA | Italy | 90127 |
110 | Novartis Investigative Site | Palermo | PA | Italy | 90146 |
111 | Novartis Investigative Site | Padova | PD | Italy | 35128 |
112 | Novartis Investigative Site | Pescara | PE | Italy | 65124 |
113 | Novartis Investigative Site | Pisa | PI | Italy | 56126 |
114 | Novartis Investigative Site | Parma | PR | Italy | 43100 |
115 | Novartis Investigative Site | Pavia | PV | Italy | 27100 |
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118 | Novartis Investigative Site | Reggio Emilia | RE | Italy | 42123 |
119 | Novartis Investigative Site | Roma | RM | Italy | 00133 |
120 | Novartis Investigative Site | Roma | RM | Italy | 00144 |
121 | Novartis Investigative Site | Roma | RM | Italy | 00161 |
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125 | Novartis Investigative Site | Orbassano | TO | Italy | 10043 |
126 | Novartis Investigative Site | Torino | TO | Italy | 10126 |
127 | Novartis Investigative Site | Treviso | TV | Italy | 31100 |
128 | Novartis Investigative Site | Udine | UD | Italy | 33100 |
129 | Novartis Investigative Site | Mirano | VE | Italy | 30035 |
130 | Novartis Investigative Site | Venezia | VE | Italy | 30174 |
131 | Novartis Investigative Site | Vicenza | VI | Italy | 36100 |
132 | Novartis Investigative Site | Verona | VR | Italy | 37126 |
133 | Novartis Investigative Site | Napoli | Italy | 80131 | |
134 | Novartis Investigative Site | Novara | Italy | 28100 | |
135 | Novartis Investigative Site | Perugia | Italy | 06129 | |
136 | Novartis Investigative Site | Bergen | Norway | NO-5021 | |
137 | Novartis Investigative Site | Oslo | Norway | NO-0310 | |
138 | Novartis Investigative Site | Chorzow | Poland | 41-500 | |
139 | Novartis Investigative Site | Gdansk | Poland | 80 952 | |
140 | Novartis Investigative Site | Katowice | Poland | 40-027 | |
141 | Novartis Investigative Site | Krakow | Poland | 30-510 | |
142 | Novartis Investigative Site | Olsztyn | Poland | 10 561 | |
143 | Novartis Investigative Site | Opole | Poland | 45-372 | |
144 | Novartis Investigative Site | Torun | Poland | 87 100 | |
145 | Novartis Investigative Site | Warszawa | Poland | 02 106 | |
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 |
178 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08036 |
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.- CAMN107AIC05
- 2012-005124-15
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
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 |
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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%
|
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)
|
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)
|
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)
|
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
|
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
|
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
|
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
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 |
novartis.email@novartis.com |
- CAMN107AIC05
- 2012-005124-15