Philadelphia Chromosome Positive (PH+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Conditions
Keywords
Adult, Chronic myelogenous leukemia (CML), Chronic myeloid leukemia (CML), Chronic myelocytic leukemia (CML), Acute Lymphoblastic Leukemia (ALL) Philadelphia chromosome positive, Acute Lymphoid Leukemia, Suboptimal molecular response
Brief summary
This study aimed to assess the optimal duration of nilotinib 300 mg twice daily (BID) consolidation treatment in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), in order that patients remained in treatment-free remission (≥MR4.0) without molecular relapse 12 months after starting the Treatment-Free Remission (TFR) phase.
Detailed description
This was a prospective, randomized, open-label, multicenter Phase III study. The study design was made up of 3 phases: * Nilotinib induction phase: 12 months * Nilotinib consolidation phase: 12 or 24 months, depending on randomization * Nilotinib treatment-free remission (TFR) phase: 24 or 36 months, depending on randomization. Subjects were enrolled into the study and were treated with nilotinib 300mg twice daily (BID) for 24 months, during the induction (12 months) and consolidation (12 months) phases. At the end of the first 24 months of treatment, participants achieving a sustained molecular response (defined as ≥ MR4.0, in 4 out of 5 real-time quantitative polymerase chain reaction (RQ-PCR) assessments, including the last assessment, in the last 12 months) were randomized on a 1:1 basis to either: 1. suspend nilotinib treatment immediately and enter the TFR phase for 36 months (Nilotinib 24-month treatment arm), or 2. continue nilotinib treatment for a further 12 months (post-randomization consolidation phase), then suspend treatment and enter the TFR phase for 24 months (Nilotinib 36-month treatment arm). Participants not achieving a sustained molecular response at 24 months from treatment start were not eligible for randomization and were treated at the discretion of the investigator according to standard practice. Information on survival, stem cell transplantation, and status of the patient's disease was collected until death or until 5 years from study entry, whichever came first. Additionally, for Nilotinib 36-month treatment arm, participants who did not achieve a sustained molecular response at 36 months from treatment start, discontinued from the study and were treated according to standard practice and followed up until death or until 5 years from study entry, whichever came first. Participants relapsing during the TFR phase entered the nilotinib re-treatment phase of the study, and were re-treated with the same dose of nilotinib as they were on before the TFR phase. These patients remained on study until the completion of the 5-year study period unless prematurely withdrawn and discontinued from the study for any reason specified in the Protocol.
Interventions
DRUGNilotinib
Participants received a daily oral nilotinib dose of 300 mg BID, given as two 150 mg capsules BID.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants received 24 months of study treatment. After 24 months of treatment, eligible participants (i.e. those deemed to have achieved sustained molecular response) were randomized to one of the two study arms on a continued open-label basis. Participants not achieving sustained molecular response after 24 months of treatment were not randomized but remained in the study until the 5-year study period was completed (Not randomized arm).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Confirmed diagnosis of chronic phase Ph+ CML * Previous first-line treatment with imatinib for a minimum of 2 years; * Patient in complete cytogenetic response; Key
Exclusion criteria
* Previous achievement of MR4.0 at study entry; * Previous treatment with other target cells inhibitors other than imatinib; * Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening; * Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction; * Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol; * History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively; * Patients who have not recovered from prior surgery; * Treatment with other investigational agents within 4 weeks of Day 1; * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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) |
Countries
Austria, Belgium, Bulgaria, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, United Kingdom
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Nilotinib 24-month Treatment Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase | 120 |
| Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase | 119 |
| Not Randomized 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. | 381 |
| Total | 620 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Re-treatment Phase | Administrative problems | 1 | 1 | 0 |
| Re-treatment Phase | Adverse Event | 8 | 4 | 0 |
| Re-treatment Phase | Death | 1 | 1 | 0 |
| Re-treatment Phase | Lost to Follow-up | 0 | 1 | 0 |
| Re-treatment Phase | Physician Decision | 0 | 1 | 0 |
| Re-treatment Phase | Unstable MR | 1 | 0 | 0 |
| Re-treatment Phase | Withdrawal by Subject | 5 | 1 | 0 |
| TFR Phase | Adverse Event | 0 | 1 | 0 |
| TFR Phase | Logistical problems | 0 | 2 | 0 |
| TFR Phase | Lost to Follow-up | 0 | 2 | 0 |
| TFR Phase | Physician Decision | 0 | 1 | 0 |
| TFR Phase | Protocol deviation | 0 | 1 | 0 |
| TFR Phase | Relapse (Loss of MMR/Confirmed loss of MR4.0) | 82 | 59 | 0 |
| TFR Phase | Withdrawal by Subject | 0 | 2 | 0 |
| Treatment Phase | Abnormal laboratory value(s) | 0 | 0 | 3 |
| Treatment Phase | Abnormal test procedure result(s) | 0 | 0 | 1 |
| Treatment Phase | Administrative problems | 0 | 0 | 1 |
| Treatment Phase | Adverse Event | 0 | 4 | 67 |
| Treatment Phase | Death | 0 | 1 | 3 |
| Treatment Phase | Included by mistake | 0 | 0 | 1 |
| Treatment Phase | Lost to Follow-up | 0 | 0 | 2 |
| Treatment Phase | New cancer (CML) therapy | 0 | 1 | 0 |
| Treatment Phase | Not randomized by mistake | 0 | 0 | 1 |
| Treatment Phase | Patient non-compliance to treatment | 0 | 0 | 3 |
| Treatment Phase | Physician Decision | 0 | 0 | 3 |
| Treatment Phase | Pregnancy | 0 | 0 | 2 |
| Treatment Phase | Protocol deviation | 0 | 0 | 3 |
| Treatment Phase | Unstable MR4.0 | 0 | 6 | 263 |
| Treatment Phase | Withdrawal by Subject | 1 | 3 | 28 |
Baseline characteristics
| Characteristic | Nilotinib 24-month Treatment | Nilotinib 36-month Treatment | Not Randomized | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 21 Participants | 73 Participants | 108 Participants |
| Age, Categorical Between 18 and 65 years | 106 Participants | 98 Participants | 308 Participants | 512 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Caucasian | 114 Participants | 112 Participants | 355 Participants | 581 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized North African descent | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 4 Participants | 13 Participants | 22 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 48 Participants | 49 Participants | 129 Participants | 226 Participants |
| Sex: Female, Male Male | 72 Participants | 70 Participants | 252 Participants | 394 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 120 | 1 / 118 | 3 / 381 | 5 / 619 |
| other Total, other adverse events | 97 / 120 | 104 / 118 | 280 / 381 | 481 / 619 |
| serious Total, serious adverse events | 33 / 120 | 27 / 118 | 76 / 381 | 136 / 619 |
Outcome results
Primary
Percentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase
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
Population: All enrolled subjects who entered the TFR phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib 24-month Treatment | Percentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase | 31.9 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Remained in Treatment Free Remission (TFR) Without Molecular Relapse 12 Months After Entering the TFR Phase | 37.5 Percentage of participants |
p-value: 0.383Chi-squared
Secondary
BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 18 after study treatment start (pre-randomization) | 0.0029 Percentage | Standard Deviation 0.00354 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 9 after study treatment start (pre-randomization) | 0.0049 Percentage | Standard Deviation 0.00809 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 3 after study treatment start (pre-randomization) | 0.0106 Percentage | Standard Deviation 0.0266 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 15 after study treatment start (pre-randomization) | 0.0035 Percentage | Standard Deviation 0.00591 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 12 after study treatment start (pre-randomization) | 0.0044 Percentage | Standard Deviation 0.00611 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Baseline | 0.1367 Percentage | Standard Deviation 0.55144 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 21 after study treatment start (pre-randomization) | 0.0028 Percentage | Standard Deviation 0.00319 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 6 after study treatment start (pre-randomization) | 0.0052 Percentage | Standard Deviation 0.00631 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 24 after study treatment start (pre-randomization) | 0.0027 Percentage | Standard Deviation 0.00424 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 18 after study treatment start (pre-randomization) | 0.0034 Percentage | Standard Deviation 0.00409 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Baseline | 0.0633 Percentage | Standard Deviation 0.1279 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 3 after study treatment start (pre-randomization) | 0.0086 Percentage | Standard Deviation 0.01155 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 6 after study treatment start (pre-randomization) | 0.0124 Percentage | Standard Deviation 0.05508 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 9 after study treatment start (pre-randomization) | 0.0046 Percentage | Standard Deviation 0.00544 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 12 after study treatment start (pre-randomization) | 0.0037 Percentage | Standard Deviation 0.0044 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 15 after study treatment start (pre-randomization) | 0.0034 Percentage | Standard Deviation 0.00389 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 21 after study treatment start (pre-randomization) | 0.0031 Percentage | Standard Deviation 0.00288 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 24 after study treatment start (pre-randomization) | 0.0029 Percentage | Standard Deviation 0.00319 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 27 after study treatment start (post-randomization) | 0.0089 Percentage | Standard Deviation 0.06119 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 30 after study treatment start (post-randomization) | 0.0111 Percentage | Standard Deviation 0.08672 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 33 after study treatment start (post-randomization) | 0.0025 Percentage | Standard Deviation 0.00439 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 36 after study treatment start (post-randomization) | 0.0025 Percentage | Standard Deviation 0.00338 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 24 after study treatment start (pre-randomization) | 0.0325 Percentage | Standard Deviation 0.0514 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 21 after study treatment start (pre-randomization) | 0.0390 Percentage | Standard Deviation 0.08271 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 12 after study treatment start (pre-randomization) | 0.0772 Percentage | Standard Deviation 0.56398 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 9 after study treatment start (pre-randomization) | 0.0573 Percentage | Standard Deviation 0.13905 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Baseline | 0.5509 Percentage | Standard Deviation 3.94256 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 15 after study treatment start (pre-randomization) | 0.0669 Percentage | Standard Deviation 0.37209 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 6 after study treatment start (pre-randomization) | 0.0530 Percentage | Standard Deviation 0.09587 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 18 after study treatment start (pre-randomization) | 0.0462 Percentage | Standard Deviation 0.12284 |
| Not Randomized | BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase | Month 3 after study treatment start (pre-randomization) | 0.0728 Percentage | Standard Deviation 0.22537 |
Secondary
BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 36 after entering the re-treatment phase | 0.0005 Percentage | — |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Day 1 after entering the re-treatment phase | 2.8246 Percentage | Standard Deviation 2.39596 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 6 after entering the re-treatment phase | 0.0095 Percentage | Standard Deviation 0.03296 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 9 after entering the re-treatment phase | 0.0259 Percentage | Standard Deviation 0.17766 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 12 after entering the re-treatment phase | 0.0088 Percentage | Standard Deviation 0.0319 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 15 after entering the re-treatment phase | 0.0061 Percentage | Standard Deviation 0.01322 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 18 after entering the re-treatment phase | 0.0105 Percentage | Standard Deviation 0.05205 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 21 after entering the re-treatment phase | 0.0051 Percentage | Standard Deviation 0.01699 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 24 after entering the re-treatment phase | 0.0038 Percentage | Standard Deviation 0.00756 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 27 after entering the re-treatment phase | 0.0033 Percentage | Standard Deviation 0.00439 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 30 after entering the re-treatment phase | 0.0113 Percentage | Standard Deviation 0.04446 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 33 after entering the re-treatment phase | 0.0029 Percentage | Standard Deviation 0.00541 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Week 6 after entering the re-treatment phase | 0.6276 Percentage | Standard Deviation 2.34231 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 3 after entering the re-treatment phase | 0.0311 Percentage | Standard Deviation 0.07265 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Day 1 after entering the re-treatment phase | 0.6301 Percentage | Standard Deviation 0.74388 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 12 after entering the re-treatment phase | 0.0047 Percentage | Standard Deviation 0.00839 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Week 6 after entering the re-treatment phase | 0.3112 Percentage | Standard Deviation 0.60279 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 24 after entering the re-treatment phase | 0.0014 Percentage | Standard Deviation 0.00197 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 3 after entering the re-treatment phase | 0.0131 Percentage | Standard Deviation 0.02359 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 15 after entering the re-treatment phase | 0.0045 Percentage | Standard Deviation 0.01176 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 6 after entering the re-treatment phase | 0.0070 Percentage | Standard Deviation 0.0133 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 21 after entering the re-treatment phase | 0.0031 Percentage | Standard Deviation 0.00342 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 9 after entering the re-treatment phase | 0.0065 Percentage | Standard Deviation 0.01099 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase | Month 18 after entering the re-treatment phase | 0.0039 Percentage | Standard Deviation 0.00581 |
Secondary
BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 1 after entering the TFR phase | 0.0042 Percentage | Standard Deviation 0.00621 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 5 after entering the TFR phase | 0.1740 Percentage | Standard Deviation 0.76123 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 6 after entering the TFR phase | 0.2219 Percentage | Standard Deviation 1.51808 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 8 after entering the TFR phase | 0.0075 Percentage | Standard Deviation 0.01403 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 10 after entering the TFR phase | 0.0062 Percentage | Standard Deviation 0.01295 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 12 after entering the TFR phase | 0.0047 Percentage | Standard Deviation 0.00665 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 15 after entering the TFR phase | 0.0030 Percentage | Standard Deviation 0.00317 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 18 after entering the TFR phase | 0.0030 Percentage | Standard Deviation 0.00384 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 21 after entering the TFR phase | 0.0036 Percentage | Standard Deviation 0.00484 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 24 after entering the TFR phase | 0.0077 Percentage | Standard Deviation 0.0291 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 27 after entering the TFR phase | 0.0024 Percentage | Standard Deviation 0.00246 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 30 after entering the TFR phase | 0.0023 Percentage | Standard Deviation 0.00281 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 33 after entering the TFR phase | 0.0079 Percentage | Standard Deviation 0.02376 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 36 after entering the TFR phase | 0.0041 Percentage | Standard Deviation 0.00767 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 2 after entering the TFR phase | 0.1162 Percentage | Standard Deviation 0.35606 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 3 after entering the TFR phase | 1.3774 Percentage | Standard Deviation 9.71909 |
| Nilotinib 24-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 4 after entering the TFR phase | 0.2667 Percentage | Standard Deviation 0.80336 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 1 after entering the TFR phase | 0.0074 Percentage | Standard Deviation 0.0213 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 21 after entering the TFR phase | 0.0041 Percentage | Standard Deviation 0.00495 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 2 after entering the TFR phase | 0.2122 Percentage | Standard Deviation 0.99372 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 10 after entering the TFR phase | 0.0039 Percentage | Standard Deviation 0.0068 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 3 after entering the TFR phase | 0.4754 Percentage | Standard Deviation 1.84649 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 18 after entering the TFR phase | 0.0027 Percentage | Standard Deviation 0.0033 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 4 after entering the TFR phase | 0.2506 Percentage | Standard Deviation 0.91197 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 12 after entering the TFR phase | 0.0027 Percentage | Standard Deviation 0.00357 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 5 after entering the TFR phase | 0.0801 Percentage | Standard Deviation 0.26739 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 24 after entering the TFR phase | 0.0047 Percentage | Standard Deviation 0.00691 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 6 after entering the TFR phase | 0.1095 Percentage | Standard Deviation 0.66322 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 15 after entering the TFR phase | 0.0043 Percentage | Standard Deviation 0.00555 |
| Nilotinib 36-month Treatment | BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase | Month 8 after entering the TFR phase | 0.0042 Percentage | Standard Deviation 0.00742 |
Secondary
Cumulative Incidence of MMR During the Post-randomization Consolidation Phase
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase | Up to 27 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase | Up to 30 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase | Up to 33 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase | Up to 36 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
Secondary
Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 27 months after study treatment start (post-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 30 months after study treatment start (post-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 33 months after study treatment start (post-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 36 months after study treatment start (post-randomization) | 100.0 Percentage of participants |
Secondary
Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase
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
Population: All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Baseline | 80.8 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 94.2 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Baseline | 86.4 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 91.5 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 90.8 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Baseline | 74.3 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 95.5 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 81.9 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 96.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 94.2 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 92.7 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 96.3 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 95.0 Percentage of participants |
Secondary
Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
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
Population: All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure who did not reach MMR at baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 69.6 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 100 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 37.5 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 71.4 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 64.3 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 29.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 77.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 85.7 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 82.7 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 80.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 86.7 Percentage of participants |
Secondary
Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase | Up to 27 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase | Up to 30 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase | Up to 33 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase | Up to 36 months after study treatment start (post-randomization) | 98.3 Percentage of participants |
Secondary
Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 27 months after study treatment start (post-randomization) | 97.9 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 30 months after study treatment start (post-randomization) | 97.9 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 33 months after study treatment start (post-randomization) | 97.9 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 36 months after study treatment start (post-randomization) | 97.9 Percentage of participants |
Secondary
Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase
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
Population: All enrolled subjects for whom written informed consent was obtained prior to any study specific procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 95.8 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 97.5 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Baseline | 23.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 89.2 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 60.8 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 99.2 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Baseline | 20.3 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 50.8 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 85.6 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 94.1 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 99.2 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 31.2 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Baseline | 6.3 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 48.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 18.4 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 55.1 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 43.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 38.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 52.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 45.7 Percentage of participants |
Secondary
Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 48.9 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 85.9 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 94.6 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 96.7 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 92.6 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 98.9 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 98.9 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 38.3 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 81.9 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 100.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 34.5 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 26.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 12.9 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 39.2 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 48.7 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 45.1 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 42.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 52.1 Percentage of participants |
Secondary
Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase | Up to 27 months after study treatment start (post-randomization) | 72.9 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase | Up to 30 months after study treatment start (post-randomization) | 78.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase | Up to 33 months after study treatment start (post-randomization) | 85.6 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase | Up to 36 months after study treatment start (post-randomization) | 88.1 Percentage of participants |
Secondary
Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 27 months after study treatment start (post-randomization) | 70.6 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 30 months after study treatment start (post-randomization) | 76.1 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 33 months after study treatment start (post-randomization) | 84.4 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Post-randomization Consolidation Phase Among Participants Without That Response at Study Entry | Up to 36 months after study treatment start (post-randomization) | 87.2 Percentage of participants |
Secondary
Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase
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
Population: All enrolled subjects for whom written informed consent was obtained before any study specific procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 61.7 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 90.0 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 81.7 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 73.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Baseline | 9.2 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 86.7 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 44.2 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 28.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 85.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 67.8 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Baseline | 7.6 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 23.7 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 43.2 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 57.6 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 78.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 82.2 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 85.6 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 89.8 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 6 months after study treatment start (pre-randomization) | 10.2 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Baseline | 1.8 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 18 months after study treatment start (pre-randomization) | 18.1 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 3 months after study treatment start (pre-randomization) | 5.8 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 24 months after study treatment start (pre-randomization) | 21.8 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 12 months after study treatment start (pre-randomization) | 15.7 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 9 months after study treatment start (pre-randomization) | 12.3 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 21 months after study treatment start (pre-randomization) | 19.9 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase | Up to 15 months after study treatment start (pre-randomization) | 16.8 Percentage of participants |
Secondary
Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 21.1 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 38.5 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 57.8 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 70.6 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 79.8 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 83.5 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 85.3 Percentage of participants |
| Nilotinib 24-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 89.0 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 54.1 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 84.4 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 65.1 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 76.1 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 80.7 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 17.4 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 38.5 Percentage of participants |
| Nilotinib 36-month Treatment | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 89.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 9 months after study treatment start (pre-randomization) | 10.7 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 6 months after study treatment start (pre-randomization) | 8.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 3 months after study treatment start (pre-randomization) | 4.0 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 12 months after study treatment start (pre-randomization) | 14.2 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 21 months after study treatment start (pre-randomization) | 18.4 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 18 months after study treatment start (pre-randomization) | 16.6 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 15 months after study treatment start (pre-randomization) | 15.2 Percentage of participants |
| Not Randomized | Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Among Participants Without That Response at Study Entry | Up to 24 months after study treatment start (pre-randomization) | 20.3 Percentage of participants |
Secondary
Overall Survival (OS) Rate During the TFR Phase of the Study.
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
Population: All enrolled subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib 24-month Treatment | Overall Survival (OS) Rate During the TFR Phase of the Study. | NA Months |
| Nilotinib 36-month Treatment | Overall Survival (OS) Rate During the TFR Phase of the Study. | NA Months |
Secondary
Percentage of Participants Who Were in MMR During TFR Phase
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
Population: All enrolled subjects who entered the TFR phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 36 after entering TFR phase | 23.5 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 1 after entering TFR phase | 97.5 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 4 after entering TFR phase | 51.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 5 after entering TFR phase | 45.4 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 6 after entering TFR phase | 42.9 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 8 after entering TFR phase | 40.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 10 after entering TFR phase | 38.7 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 12 after entering TFR phase | 36.1 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 15 after entering TFR phase | 35.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 18 after entering TFR phase | 35.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 24 after entering TFR phase | 31.9 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 27 after entering TFR phase | 31.9 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 30 after entering TFR phase | 31.9 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 33 after entering TFR phase | 30.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 21 after entering TFR phase | 34.5 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 2 after entering TFR phase | 84.9 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 3 after entering TFR phase | 62.2 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 1 after entering TFR phase | 94.2 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 24 after entering TFR phase | 35.6 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 2 after entering TFR phase | 80.8 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 10 after entering TFR phase | 42.3 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 3 after entering TFR phase | 61.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 18 after entering TFR phase | 39.4 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 4 after entering TFR phase | 53.8 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 12 after entering TFR phase | 39.4 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 5 after entering TFR phase | 46.2 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 21 after entering TFR phase | 38.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 6 after entering TFR phase | 43.3 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 15 after entering TFR phase | 39.4 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MMR During TFR Phase | Month 8 after entering TFR phase | 43.3 Percentage of participants |
Secondary
Percentage of Participants Who Were in MR4.0 During the TFR Phase
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
Population: All enrolled subjects who entered the TFR phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 1 after entering TFR phase | 87.4 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 5 after entering TFR phase | 32.8 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 6 after entering TFR phase | 33.6 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 8 after entering TFR phase | 34.5 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 10 after entering TFR phase | 35.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 12 after entering TFR phase | 31.9 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 15 after entering TFR phase | 34.5 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 18 after entering TFR phase | 33.6 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 21 after entering TFR phase | 30.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 24 after entering TFR phase | 29.4 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 27 after entering TFR phase | 31.1 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 30 after entering TFR phase | 30.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 33 after entering TFR phase | 27.7 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 36 after entering TFR phase | 26.1 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 2 after entering TFR phase | 58.0 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 3 after entering TFR phase | 39.5 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 4 after entering TFR phase | 36.1 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 1 after entering TFR phase | 83.7 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 21 after entering TFR phase | 32.7 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 2 after entering TFR phase | 56.7 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 10 after entering TFR phase | 38.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 3 after entering TFR phase | 42.3 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 18 after entering TFR phase | 38.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 4 after entering TFR phase | 42.3 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 12 after entering TFR phase | 37.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 5 after entering TFR phase | 41.3 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 24 after entering TFR phase | 30.8 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 6 after entering TFR phase | 38.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 15 after entering TFR phase | 34.6 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.0 During the TFR Phase | Month 8 after entering TFR phase | 40.4 Percentage of participants |
Secondary
Percentage of Participants Who Were in MR4.5 During the TFR Phase
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
Population: All enrolled subjects who entered the TFR phase
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 3 after entering TFR phase | 21.8 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 18 after entering TFR phase | 25.2 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 21 after entering TFR phase | 22.7 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 24 after entering TFR phase | 24.4 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 27 after entering TFR phase | 21.8 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 30 after entering TFR phase | 22.7 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 33 after entering TFR phase | 19.3 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 36 after entering TFR phase | 16.8 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 6 after entering TFR phase | 17.6 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 12 after entering TFR phase | 20.2 Percentage of participants |
| Nilotinib 24-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 15 after entering TFR phase | 18.5 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 3 after entering TFR phase | 26.9 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 21 after entering TFR phase | 22.1 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 6 after entering TFR phase | 28.8 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 18 after entering TFR phase | 26.9 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 12 after entering TFR phase | 26.9 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 24 after entering TFR phase | 20.2 Percentage of participants |
| Nilotinib 36-month Treatment | Percentage of Participants Who Were in MR4.5 During the TFR Phase | Month 15 after entering TFR phase | 23.1 Percentage of participants |
Secondary
Progression-free Survival (PFS) During the TFR Phase of the Study.
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
Population: All enrolled subjects who entered the TFR phase
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib 24-month Treatment | Progression-free Survival (PFS) During the TFR Phase of the Study. | NA Months |
| Nilotinib 36-month Treatment | Progression-free Survival (PFS) During the TFR Phase of the Study. | NA Months |
Secondary
Treatment -Free Survival (TFS) During the TFR Phase of the Study
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
Population: All enrolled subjects who entered the TFR phase
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib 24-month Treatment | Treatment -Free Survival (TFS) During the TFR Phase of the Study | 4.1 Months |
| Nilotinib 36-month Treatment | Treatment -Free Survival (TFS) During the TFR Phase of the Study | 4.2 Months |
Post Hoc
All Collected Deaths
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
Population: All enrolled participants for whom informed consent was obtained prior to any study specific procedure were included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib 24-month Treatment | All Collected Deaths | On-treatment deaths | 1 Participants |
| Nilotinib 24-month Treatment | All Collected Deaths | Total deaths | 1 Participants |
| Nilotinib 36-month Treatment | All Collected Deaths | On-treatment deaths | 1 Participants |
| Nilotinib 36-month Treatment | All Collected Deaths | Total deaths | 3 Participants |
| Not Randomized | All Collected Deaths | On-treatment deaths | 3 Participants |
| Not Randomized | All Collected Deaths | Total deaths | 10 Participants |