Trial Outcomes & Findings for A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML. (NCT NCT01743989)

Last Updated: 2021-07-15

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

620 participants

Primary outcome timeframe

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

Results posted on

2021-07-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Nilotinib 24-month Treatment Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Treatment Phase STARTED	120	119	381
Treatment Phase Participants Who Signed Informed Consent	120	118	381
Treatment Phase COMPLETED	119	104	0
Treatment Phase NOT COMPLETED	1	15	381
TFR Phase STARTED	119	104	0
TFR Phase COMPLETED	37	36	0
TFR Phase NOT COMPLETED	82	68	0
Re-treatment Phase STARTED	74	55	0
Re-treatment Phase COMPLETED	58	46	0
Re-treatment Phase NOT COMPLETED	16	9	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Nilotinib 24-month Treatment Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Treatment Phase Unstable MR4.0	0	6	263
Treatment Phase Adverse Event	0	4	67
Treatment Phase Withdrawal by Subject	1	3	28
Treatment Phase Death	0	1	3
Treatment Phase Abnormal laboratory value(s)	0	0	3
Treatment Phase Protocol deviation	0	0	3
Treatment Phase Pregnancy	0	0	2
Treatment Phase Lost to Follow-up	0	0	2
Treatment Phase Abnormal test procedure result(s)	0	0	1
Treatment Phase Administrative problems	0	0	1
Treatment Phase New cancer (CML) therapy	0	1	0
Treatment Phase Physician Decision	0	0	3
Treatment Phase Patient non-compliance to treatment	0	0	3
Treatment Phase Not randomized by mistake	0	0	1
Treatment Phase Included by mistake	0	0	1
TFR Phase Relapse (Loss of MMR/Confirmed loss of MR4.0)	82	59	0
TFR Phase Adverse Event	0	1	0
TFR Phase Lost to Follow-up	0	2	0
TFR Phase Physician Decision	0	1	0
TFR Phase Logistical problems	0	2	0
TFR Phase Protocol deviation	0	1	0
TFR Phase Withdrawal by Subject	0	2	0
Re-treatment Phase Adverse Event	8	4	0
Re-treatment Phase Death	1	1	0
Re-treatment Phase Administrative problems	1	1	0
Re-treatment Phase Withdrawal by Subject	5	1	0
Re-treatment Phase Unstable MR	1	0	0
Re-treatment Phase Physician Decision	0	1	0
Re-treatment Phase Lost to Follow-up	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=381 Participants Participants were treated with nilotinib 300mg BID for 24 months, but did not achieve a sustained molecular response after 24 months of treatment and were not randomized.	Total n=620 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	106 Participants n=5 Participants	98 Participants n=7 Participants	308 Participants n=5 Participants	512 Participants n=4 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	21 Participants n=7 Participants	73 Participants n=5 Participants	108 Participants n=4 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	49 Participants n=7 Participants	129 Participants n=5 Participants	226 Participants n=4 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	70 Participants n=7 Participants	252 Participants n=5 Participants	394 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	114 Participants n=5 Participants	112 Participants n=7 Participants	355 Participants n=5 Participants	581 Participants n=4 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Native American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized North African descent	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants	22 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 23.7 to 41.1	37.5 Percentage of participants Interval 28.2 to 47.5	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=23 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=16 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=98 Participants 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.
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 Interval 47.1 to 86.8	37.5 Percentage of participants Interval 15.2 to 64.6	29.6 Percentage of participants Interval 20.8 to 39.7
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	64.3 Percentage of participants Interval 54.0 to 73.7
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	71.4 Percentage of participants Interval 61.4 to 80.1
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	77.6 Percentage of participants Interval 68.0 to 85.4
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	80.6 Percentage of participants Interval 71.4 to 87.9
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	82.7 Percentage of participants Interval 73.7 to 89.6
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	85.7 Percentage of participants Interval 77.2 to 92.0
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 Interval 85.2 to 100.0	100.0 Percentage of participants Interval 79.4 to 100.0	86.7 Percentage of participants Interval 78.4 to 92.7

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=16 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 79.4 to 100.0	—	—
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 Interval 79.4 to 100.0	—	—
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 Interval 79.4 to 100.0	—	—
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 Interval 79.4 to 100.0	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=92 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=94 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=357 Participants 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.
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 Interval 38.3 to 59.6	38.3 Percentage of participants Interval 28.5 to 48.9	12.9 Percentage of participants Interval 9.6 to 16.8
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 Interval 77.1 to 92.3	81.9 Percentage of participants Interval 72.6 to 89.1	26.6 Percentage of participants Interval 22.1 to 31.5
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 Interval 87.8 to 98.2	92.6 Percentage of participants Interval 85.3 to 97.0	34.5 Percentage of participants Interval 29.5 to 39.6
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 Interval 90.8 to 99.3	98.9 Percentage of participants Interval 94.2 to 100.0	39.2 Percentage of participants Interval 34.1 to 44.5
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 Interval 96.1 to 100.0	98.9 Percentage of participants Interval 94.2 to 100.0	42.0 Percentage of participants Interval 36.8 to 47.3
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 Interval 96.1 to 100.0	100.0 Percentage of participants Interval 96.2 to 100.0	45.1 Percentage of participants Interval 39.9 to 50.4
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 Interval 96.1 to 100.0	100.0 Percentage of participants Interval 96.2 to 100.0	48.7 Percentage of participants Interval 43.4 to 54.1
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 Interval 96.1 to 100.0	100.0 Percentage of participants Interval 96.2 to 100.0	52.1 Percentage of participants Interval 46.8 to 57.4

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=94 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 92.5 to 99.7	—	—
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 Interval 92.5 to 99.7	—	—
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 Interval 92.5 to 99.7	—	—
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 Interval 92.5 to 99.7	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=109 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=109 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=374 Participants 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.
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 Interval 81.6 to 94.2	89.0 Percentage of participants Interval 81.6 to 94.2	20.3 Percentage of participants Interval 16.4 to 24.8
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 Interval 13.9 to 30.0	17.4 Percentage of participants Interval 10.8 to 25.9	4.0 Percentage of participants Interval 2.3 to 6.5
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 Interval 29.4 to 48.3	38.5 Percentage of participants Interval 29.4 to 48.3	8.6 Percentage of participants Interval 5.9 to 11.9
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 Interval 48.0 to 67.2	54.1 Percentage of participants Interval 44.3 to 63.7	10.7 Percentage of participants Interval 7.8 to 14.3
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 Interval 61.2 to 79.0	65.1 Percentage of participants Interval 55.4 to 74.0	14.2 Percentage of participants Interval 10.8 to 18.1
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 Interval 71.1 to 86.9	76.1 Percentage of participants Interval 67.0 to 83.8	15.2 Percentage of participants Interval 11.8 to 19.3
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 Interval 75.2 to 89.9	80.7 Percentage of participants Interval 72.1 to 87.7	16.6 Percentage of participants Interval 13.0 to 20.7
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 Interval 77.3 to 91.4	84.4 Percentage of participants Interval 76.2 to 90.6	18.4 Percentage of participants Interval 14.7 to 22.8

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=109 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 61.2 to 79.0	—	—
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 Interval 67.0 to 83.8	—	—
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 Interval 76.2 to 90.6	—	—
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 Interval 79.4 to 92.8	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=381 Participants 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.
Cumulative Incidence of MMR During the Pre-randomization Induction/Consolidation Phase Baseline	80.8 Percentage of participants Interval 72.6 to 87.4	86.4 Percentage of participants Interval 78.9 to 92.1	74.3 Percentage of participants Interval 69.6 to 78.6
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 Interval 88.4 to 97.6	91.5 Percentage of participants Interval 85.0 to 95.9	81.9 Percentage of participants Interval 77.7 to 85.6
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	90.8 Percentage of participants Interval 87.5 to 93.5
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	92.7 Percentage of participants Interval 89.6 to 95.1
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	94.2 Percentage of participants Interval 91.4 to 96.4
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	95.0 Percentage of participants Interval 92.3 to 97.0
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	95.5 Percentage of participants Interval 93.0 to 97.4
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	96.3 Percentage of participants Interval 93.9 to 98.0
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	96.6 Percentage of participants Interval 94.2 to 98.2

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 94.0 to 99.8	—	—
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 Interval 94.0 to 99.8	—	—
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 Interval 94.0 to 99.8	—	—
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 Interval 94.0 to 99.8	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=381 Participants 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.
Cumulative Incidence of MR4.0 During the Pre-randomization Induction/Consolidation Phase Baseline	23.3 Percentage of participants Interval 16.1 to 31.9	20.3 Percentage of participants Interval 13.5 to 28.7	6.3 Percentage of participants Interval 4.1 to 9.2
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 Interval 51.5 to 69.6	50.8 Percentage of participants Interval 41.5 to 60.2	18.4 Percentage of participants Interval 14.6 to 22.6
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 Interval 82.2 to 94.1	85.6 Percentage of participants Interval 77.9 to 91.4	31.2 Percentage of participants Interval 26.6 to 36.2
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 Interval 90.5 to 98.6	94.1 Percentage of participants Interval 88.2 to 97.6	38.6 Percentage of participants Interval 33.7 to 43.7
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 Interval 92.9 to 99.5	99.2 Percentage of participants Interval 95.4 to 100.0	43.0 Percentage of participants Interval 38.0 to 48.2
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 Interval 97.0 to 100.0	99.2 Percentage of participants Interval 95.4 to 100.0	45.7 Percentage of participants Interval 40.6 to 50.8
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	48.6 Percentage of participants Interval 43.4 to 53.7
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	52.0 Percentage of participants Interval 46.8 to 57.1
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 Interval 97.0 to 100.0	100.0 Percentage of participants Interval 96.9 to 100.0	55.1 Percentage of participants Interval 50.0 to 60.2

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 94.0 to 99.8	—	—
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 Interval 94.0 to 99.8	—	—
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 Interval 94.0 to 99.8	—	—
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 Interval 94.0 to 99.8	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=381 Participants 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.
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 Interval 77.3 to 90.9	82.2 Percentage of participants Interval 74.1 to 88.6	18.1 Percentage of participants Interval 14.4 to 22.4
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 Interval 79.3 to 92.2	85.6 Percentage of participants Interval 77.9 to 91.4	19.9 Percentage of participants Interval 16.1 to 24.3
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 Interval 83.2 to 94.7	89.8 Percentage of participants Interval 82.9 to 94.6	21.8 Percentage of participants Interval 17.7 to 26.3
Cumulative Incidence of MR4.5 During the Pre-randomization Induction/Consolidation Phase Baseline	9.2 Percentage of participants Interval 4.7 to 15.8	7.6 Percentage of participants Interval 3.6 to 14.0	1.8 Percentage of participants Interval 0.7 to 3.8
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 Interval 20.5 to 37.3	23.7 Percentage of participants Interval 16.4 to 32.4	5.8 Percentage of participants Interval 3.7 to 8.6
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 Interval 35.1 to 53.5	43.2 Percentage of participants Interval 34.1 to 52.7	10.2 Percentage of participants Interval 7.4 to 13.7
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 Interval 52.4 to 70.4	57.6 Percentage of participants Interval 48.2 to 66.7	12.3 Percentage of participants Interval 9.2 to 16.1
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 Interval 64.5 to 81.0	67.8 Percentage of participants Interval 58.6 to 76.1	15.7 Percentage of participants Interval 12.2 to 19.8
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 Interval 73.6 to 88.1	78.0 Percentage of participants Interval 69.4 to 85.1	16.8 Percentage of participants Interval 13.2 to 20.9

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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 Interval 63.9 to 80.7	—	—
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 Interval 69.4 to 85.1	—	—
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 Interval 77.9 to 91.4	—	—
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 Interval 80.9 to 93.4	—	—

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Percentage of Participants Who Were in MMR During TFR Phase Month 1 after entering TFR phase	97.5 Percentage of participants Interval 92.8 to 99.5	94.2 Percentage of participants Interval 87.9 to 97.9	—
Percentage of Participants Who Were in MMR During TFR Phase Month 2 after entering TFR phase	84.9 Percentage of participants Interval 77.2 to 90.8	80.8 Percentage of participants Interval 71.9 to 87.8	—
Percentage of Participants Who Were in MMR During TFR Phase Month 3 after entering TFR phase	62.2 Percentage of participants Interval 52.8 to 70.9	61.5 Percentage of participants Interval 51.5 to 70.9	—
Percentage of Participants Who Were in MMR During TFR Phase Month 4 after entering TFR phase	51.3 Percentage of participants Interval 41.9 to 60.5	53.8 Percentage of participants Interval 43.8 to 63.7	—
Percentage of Participants Who Were in MMR During TFR Phase Month 5 after entering TFR phase	45.4 Percentage of participants Interval 36.2 to 54.8	46.2 Percentage of participants Interval 36.3 to 56.2	—
Percentage of Participants Who Were in MMR During TFR Phase Month 6 after entering TFR phase	42.9 Percentage of participants Interval 33.8 to 52.3	43.3 Percentage of participants Interval 33.6 to 53.4	—
Percentage of Participants Who Were in MMR During TFR Phase Month 8 after entering TFR phase	40.3 Percentage of participants Interval 31.5 to 49.7	43.3 Percentage of participants Interval 33.6 to 53.4	—
Percentage of Participants Who Were in MMR During TFR Phase Month 10 after entering TFR phase	38.7 Percentage of participants Interval 29.9 to 48.0	42.3 Percentage of participants Interval 32.7 to 52.4	—
Percentage of Participants Who Were in MMR During TFR Phase Month 12 after entering TFR phase	36.1 Percentage of participants Interval 27.5 to 45.5	39.4 Percentage of participants Interval 30.0 to 49.5	—
Percentage of Participants Who Were in MMR During TFR Phase Month 15 after entering TFR phase	35.3 Percentage of participants Interval 26.8 to 44.6	39.4 Percentage of participants Interval 30.0 to 49.5	—
Percentage of Participants Who Were in MMR During TFR Phase Month 18 after entering TFR phase	35.3 Percentage of participants Interval 26.8 to 44.6	39.4 Percentage of participants Interval 30.0 to 49.5	—
Percentage of Participants Who Were in MMR During TFR Phase Month 21 after entering TFR phase	34.5 Percentage of participants Interval 26.0 to 43.7	38.5 Percentage of participants Interval 29.1 to 48.5	—
Percentage of Participants Who Were in MMR During TFR Phase Month 24 after entering TFR phase	31.9 Percentage of participants Interval 23.7 to 41.1	35.6 Percentage of participants Interval 26.4 to 45.6	—
Percentage of Participants Who Were in MMR During TFR Phase Month 27 after entering TFR phase	31.9 Percentage of participants Interval 23.7 to 41.1	—	—
Percentage of Participants Who Were in MMR During TFR Phase Month 30 after entering TFR phase	31.9 Percentage of participants Interval 23.7 to 41.1	—	—
Percentage of Participants Who Were in MMR During TFR Phase Month 33 after entering TFR phase	30.3 Percentage of participants Interval 22.2 to 39.4	—	—
Percentage of Participants Who Were in MMR During TFR Phase Month 36 after entering TFR phase	23.5 Percentage of participants Interval 16.2 to 32.2	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 1 after entering TFR phase	87.4 Percentage of participants Interval 80.1 to 92.8	83.7 Percentage of participants Interval 75.1 to 90.2	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 2 after entering TFR phase	58.0 Percentage of participants Interval 48.6 to 67.0	56.7 Percentage of participants Interval 46.7 to 66.4	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 3 after entering TFR phase	39.5 Percentage of participants Interval 30.7 to 48.9	42.3 Percentage of participants Interval 32.7 to 52.4	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 4 after entering TFR phase	36.1 Percentage of participants Interval 27.5 to 45.5	42.3 Percentage of participants Interval 32.7 to 52.4	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 5 after entering TFR phase	32.8 Percentage of participants Interval 24.5 to 42.0	41.3 Percentage of participants Interval 31.8 to 51.4	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 6 after entering TFR phase	33.6 Percentage of participants Interval 25.2 to 42.9	38.5 Percentage of participants Interval 29.1 to 48.5	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 8 after entering TFR phase	34.5 Percentage of participants Interval 26.0 to 43.7	40.4 Percentage of participants Interval 30.9 to 50.5	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 10 after entering TFR phase	35.3 Percentage of participants Interval 26.8 to 44.6	38.5 Percentage of participants Interval 29.1 to 48.5	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 12 after entering TFR phase	31.9 Percentage of participants Interval 23.7 to 41.1	37.5 Percentage of participants Interval 28.2 to 47.5	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 15 after entering TFR phase	34.5 Percentage of participants Interval 26.0 to 43.7	34.6 Percentage of participants Interval 25.6 to 44.6	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 18 after entering TFR phase	33.6 Percentage of participants Interval 25.2 to 42.9	38.5 Percentage of participants Interval 29.1 to 48.5	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 21 after entering TFR phase	30.3 Percentage of participants Interval 22.2 to 39.4	32.7 Percentage of participants Interval 23.8 to 42.6	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 24 after entering TFR phase	29.4 Percentage of participants Interval 21.4 to 38.5	30.8 Percentage of participants Interval 22.1 to 40.6	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 27 after entering TFR phase	31.1 Percentage of participants Interval 22.9 to 40.2	—	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 30 after entering TFR phase	30.3 Percentage of participants Interval 22.2 to 39.4	—	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 33 after entering TFR phase	27.7 Percentage of participants Interval 19.9 to 36.7	—	—
Percentage of Participants Who Were in MR4.0 During the TFR Phase Month 36 after entering TFR phase	26.1 Percentage of participants Interval 18.4 to 34.9	—	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 3 after entering TFR phase	21.8 Percentage of participants Interval 14.8 to 30.4	26.9 Percentage of participants Interval 18.7 to 36.5	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 6 after entering TFR phase	17.6 Percentage of participants Interval 11.3 to 25.7	28.8 Percentage of participants Interval 20.4 to 38.6	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 12 after entering TFR phase	20.2 Percentage of participants Interval 13.4 to 28.5	26.9 Percentage of participants Interval 18.7 to 36.5	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 15 after entering TFR phase	18.5 Percentage of participants Interval 12.0 to 26.6	23.1 Percentage of participants Interval 15.4 to 32.4	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 18 after entering TFR phase	25.2 Percentage of participants Interval 17.7 to 34.0	26.9 Percentage of participants Interval 18.7 to 36.5	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 21 after entering TFR phase	22.7 Percentage of participants Interval 15.5 to 31.3	22.1 Percentage of participants Interval 14.6 to 31.3	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 24 after entering TFR phase	24.4 Percentage of participants Interval 17.0 to 33.1	20.2 Percentage of participants Interval 13.0 to 29.2	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 27 after entering TFR phase	21.8 Percentage of participants Interval 14.8 to 30.4	—	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 30 after entering TFR phase	22.7 Percentage of participants Interval 15.5 to 31.3	—	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 33 after entering TFR phase	19.3 Percentage of participants Interval 12.7 to 27.6	—	—
Percentage of Participants Who Were in MR4.5 During the TFR Phase Month 36 after entering TFR phase	16.8 Percentage of participants Interval 10.6 to 24.8	—	—

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=381 Participants 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.
BCR-ABL Ratio (Expressed as a Percentage) During the Induction/Consolidation Phase Baseline	0.1367 Percentage Standard Deviation 0.55144	0.0633 Percentage Standard Deviation 0.12790	0.5509 Percentage Standard Deviation 3.94256
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 0.02660	0.0086 Percentage Standard Deviation 0.01155	0.0728 Percentage Standard Deviation 0.22537
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	0.0124 Percentage Standard Deviation 0.05508	0.0530 Percentage Standard Deviation 0.09587
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	0.0046 Percentage Standard Deviation 0.00544	0.0573 Percentage Standard Deviation 0.13905
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	0.0037 Percentage Standard Deviation 0.00440	0.0772 Percentage Standard Deviation 0.56398
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	0.0034 Percentage Standard Deviation 0.00389	0.0669 Percentage Standard Deviation 0.37209
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	0.0034 Percentage Standard Deviation 0.00409	0.0462 Percentage Standard Deviation 0.12284
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	0.0031 Percentage Standard Deviation 0.00288	0.0390 Percentage Standard Deviation 0.08271
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	0.0029 Percentage Standard Deviation 0.00319	0.0325 Percentage Standard Deviation 0.05140
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	—
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	—
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	—
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	—

SECONDARY outcome

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.

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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	0.2506 Percentage Standard Deviation 0.91197	—
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	0.0801 Percentage Standard Deviation 0.26739	—
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	0.1095 Percentage Standard Deviation 0.66322	—
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	0.0042 Percentage Standard Deviation 0.00742	—
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	0.0074 Percentage Standard Deviation 0.02130	—
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	0.2122 Percentage Standard Deviation 0.99372	—
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	0.4754 Percentage Standard Deviation 1.84649	—
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	0.0039 Percentage Standard Deviation 0.00680	—
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	0.0027 Percentage Standard Deviation 0.00357	—
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	0.0043 Percentage Standard Deviation 0.00555	—
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	0.0027 Percentage Standard Deviation 0.00330	—
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	0.0041 Percentage Standard Deviation 0.00495	—
BCR-ABL Ratio (Expressed as a Percentage) During the TFR Phase Month 24 after entering the TFR phase	0.0077 Percentage Standard Deviation 0.02910	0.0047 Percentage Standard Deviation 0.00691	—
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	—	—
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	—	—
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	—	—
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	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=74 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=55 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
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	0.6301 Percentage Standard Deviation 0.74388	—
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	0.3112 Percentage Standard Deviation 0.60279	—
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	0.0131 Percentage Standard Deviation 0.02359	—
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	0.0070 Percentage Standard Deviation 0.01330	—
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	0.0065 Percentage Standard Deviation 0.01099	—
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 0.03190	0.0047 Percentage Standard Deviation 0.00839	—
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	0.0045 Percentage Standard Deviation 0.01176	—
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	0.0039 Percentage Standard Deviation 0.00581	—
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	0.0031 Percentage Standard Deviation 0.00342	—
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	0.0014 Percentage Standard Deviation 0.00197	—
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	—	—
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	—	—
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	—	—
BCR-ABL Ratio (Expressed as a Percentage) During the Nilotinib Re-treatment Phase Month 36 after entering the re-treatment phase	0.0005 Percentage Standard Deviation NA NA: Not estimable due to the low number of participants analyzed	—	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Progression-free Survival (PFS) During the TFR Phase of the Study.	NA Months NA: Not estimable due to the low number of participants with events	NA Months NA: Not estimable due to the low number of participants with events	—

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=104 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Treatment -Free Survival (TFS) During the TFR Phase of the Study	4.1 Months Interval 3.7 to 5.5	4.2 Months Interval 3.7 to 19.7	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=119 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	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.
Overall Survival (OS) Rate During the TFR Phase of the Study.	NA Months NA: Not estimable due to the low number of participants with events	NA Months NA: Not estimable due to the low number of participants with events	—

POST_HOC outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Nilotinib 24-month Treatment n=120 Participants Participants were treated with nilotinib 300mg BID for 24 months and, thereafter, entered the 36-month TFR phase	Nilotinib 36-month Treatment n=118 Participants Participants were treated with nilotinib 300mg BID for 36 months and, thereafter, entered the 24-month TFR phase	Not Randomized n=381 Participants 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.
All Collected Deaths On-treatment deaths	1 Participants	1 Participants	3 Participants
All Collected Deaths Total deaths	1 Participants	3 Participants	10 Participants

Adverse Events

Nilotinib 24-month Treatment

Serious events: 33 serious events

Other events: 97 other events

Deaths: 1 deaths

Nilotinib 36-month Treatment

Serious events: 27 serious events

Other events: 104 other events

Deaths: 1 deaths

Not Randomized

Serious events: 76 serious events

Other events: 280 other events

Deaths: 3 deaths

Total

Serious events: 136 serious events

Other events: 481 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Study director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER