Trial Outcomes & Findings for Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients. (NCT NCT01844765)

Last Updated: 2021-04-22

Results Overview

MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. A patient was counted as having MMR at 6 cycles if the patient met the MMR criteria at the Cycle 6 Visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

6 cycles

Results posted on

2021-04-22

Participant Flow

3 cohorts were planned based on disease classification. In 1 cohort no patients (pts) were enrolled so results presented are based on 2 cohorts. 34 imatinib/dasatinib resistant/intolerant CML-CP pts \& 25 newly diagnosed CML-CP pts were enrolled. 1 imatinib/dasatinib resistant/intolerant pt did not receive study drug \& was excluded from analysis.

Minimum 50 pediatric patients (pts) to be enrolled in the study. At least 15 were to be Ph+ CML-CP pts resistant/intolerant to either imatinib or dasatinib, \& at least 15 newly diagnosed Ph+ CML-CP pts. There was no requirement on the minimum number of pts to be enrolled in the Cohort of CML-AP resistant/intolerant to either imatinib or dasatinib.

Participant milestones

Participant milestones
Measure	Resistant/Intolerant Ph+ CML in CP Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis
Overall Study STARTED	34	25
Overall Study Treated	33	25
Overall Study Untreated	1	0
Overall Study COMPLETED	19	10
Overall Study NOT COMPLETED	15	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Resistant/Intolerant Ph+ CML in CP Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis
Overall Study Adverse Event	6	8
Overall Study Withdrawal by Subject	2	3
Overall Study Disease progression	1	0
Overall Study Administrative problems	3	4
Overall Study Protocol deviation	2	0
Overall Study Untreated	1	0

Baseline Characteristics

Full Analysis Set (FAS): All patients who received at least one dose of study medication.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP n=25 Participants Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis	Total n=58 Participants Total of all reporting groups
Age, Customized 1 to < 12 years	12 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	6 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	18 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Age, Customized 12 to < 18 years	21 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	19 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	40 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Sex: Female, Male Female	12 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	12 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	24 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Sex: Female, Male Male	21 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	13 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	34 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Race/Ethnicity, Customized Caucasian	12 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	18 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	30 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Race/Ethnicity, Customized Black	3 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	0 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	3 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Race/Ethnicity, Customized Asian	16 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	7 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	23 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Race/Ethnicity, Customized Native American	1 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	0 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	1 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.
Race/Ethnicity, Customized Other	1 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	0 Participants n=7 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.	1 Participants n=5 Participants • Full Analysis Set (FAS): All patients who received at least one dose of study medication.

PRIMARY outcome

Timeframe: 6 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Rate of Major Molecular Response (MMR) at 6 Cycles for Ph+ CML CP Patients Resistant or Intolerant to Imatinib or Dasatinib	39.4 Percentage of participants Interval 22.9 to 57.9	—

PRIMARY outcome

Timeframe: 12 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. A patient was counted as having MMR by 12 cycles if the patient met the MMR criteria at least once at any time between first study drug intake and Cycle 12 visit included.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
MMR Rate by 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients	64.0 Percentage of participants Interval 42.5 to 82.0	—

PRIMARY outcome

Timeframe: 12 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Rate of Complete Cytogenic Response (CCyR) at 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients	64.0 Percentage of participants Interval 42.5 to 82.0	—

SECONDARY outcome

Timeframe: By 3, 6, 9 , 12, 24, 36, 48, 66 cycles ( 1 cycle = 28 days)

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Major molecular response (MMR) was defined as BCR-ABL/ABL % ≤ 0.1% by IS as measured by RQ-PCR, confirmed by duplicate analysis of the same sample.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 3	36.4 Percentage of participants Interval 20.4 to 54.9	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 6	45.5 Percentage of participants Interval 28.1 to 63.6	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 9	51.5 Percentage of participants Interval 33.5 to 69.2	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 12	57.6 Percentage of participants Interval 39.2 to 74.5	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 18	57.6 Percentage of participants Interval 39.2 to 74.5	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 24	57.6 Percentage of participants Interval 39.2 to 74.5	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 36	57.6 Percentage of participants Interval 39.2 to 74.5	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 48	60.6 Percentage of participants Interval 42.1 to 77.1	—
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib By cycle 66	60.6 Percentage of participants Interval 42.1 to 77.1	—

SECONDARY outcome

Timeframe: by 3, 6, 9, 12, 24, 36, 48, 66 cycles (1 cycle = 28 days)

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Major molecular response (MMR) was defined as BCR-ABL/ABL % ≤ 0.1% by IS as measured by RQ-PCR, confirmed by duplicate analysis of the same sample.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 3	12.0 Percentage of participants Interval 2.5 to 31.2	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 6	52.0 Percentage of participants Interval 31.3 to 72.2	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 9	56.0 Percentage of participants Interval 34.9 to 75.6	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 12	64.0 Percentage of participants Interval 42.5 to 82.0	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 18	68.0 Percentage of participants Interval 46.5 to 85.1	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 24	68.0 Percentage of participants Interval 46.5 to 85.1	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 36	76.0 Percentage of participants Interval 54.9 to 90.6	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 48	76.0 Percentage of participants Interval 54.9 to 90.6	—
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients By cycle 66	76.0 Percentage of participants Interval 54.9 to 90.6	—

SECONDARY outcome

Timeframe: up to 66 cycles (1 cycle = 28 days)

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. BCR-ABL ratio by percentage: \> 0.0032 to ≤ 0.01% is equal to a log reduction category of \>= 4 to \<4.5 -log reduction (MR4); BCR-ABL ratio by percentage: \<=0.0032% is equal to a log reduction category of \>= 4.5-log reduction (MMR4.5)

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall <=0.0032%	12.1 Percentage of participants	—
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall > 0.0032% - ≤ 0.01%	15.2 Percentage of participants	—
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall >0.01% - ≤ 0.1%	33.3 Percentage of participants	—
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall >0.1% - ≤ 1%	21.2 Percentage of participants	—
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall >1% - ≤ 10%	9.1 Percentage of participants	—
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall > 10%	6.1 Percentage of participants	—
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall Atypical transcripts at baseline	3.0 Percentage of participants	—

SECONDARY outcome

Timeframe: up to 66 cycles (1 cycle = 28 days)

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. BCR-ABL ratio by percentage: \> 0.0032 to ≤ 0.01% is equal to a log reduction category of \>= 4 to \<4.5 -log reduction (MR4); BCR-ABL ratio by percentage: \<=0.0032% is equal to a log reduction category of \>= 4.5-log reduction (MMR4.5)

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall ≤ 0.0032%	44.0 Percentage of participants	—
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall >0.0032% - ≤ 0.01%	12.0 Percentage of participants	—
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall >0.01% - ≤ 0.1%	20.0 Percentage of participants	—
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall >0.1% - ≤ 1%	8.0 Percentage of participants	—
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall >1% - ≤ 10%	8.0 Percentage of participants	—
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall >10%	8.0 Percentage of participants	—

SECONDARY outcome

Timeframe: From first dosing to the first MMR within 66 cycles period

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

Time from first study drug intake to first MMR amongst imatinib or dasatinib resistant or intolerant patients with CML-CP computed only for patients who achieved MMR.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=20 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Time to First MMR Among Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients Who Achieved MMR	2.79 months Interval 0.03 to 5.75	—

SECONDARY outcome

Timeframe: From first dosing to the first MMR within 66 cycles period

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

Time to MMR is the time from first study drug intake to first major molecular response computed only for participants who achieved MMR.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=19 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Time to First MMR Among Newly Diagnosed Ph+ CML-CP Patients Who Achieved MMR	5.59 Months Interval 5.52 to 10.84	—

SECONDARY outcome

Timeframe: from MMR until confirmed loss of MMR (Assessed up to 66 cycles)

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

Duration of MMR is defined as the time between the date of the first MMR and the date of confirmed loss of MMR (i.e. the earliest of confirmed loss of MMR, CML-related death or progression to AP or BC). Participants without loss of MMR were censored at the last molecular assessment date.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=20 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Duration of First MMR Among Patients Who Were Resistant or Intolerant to Either Imatinib or Dasatinib Who Achieved MMR	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: from MMR until confirmed loss of MMR (Assessed up to 66 cycles)es)

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=19 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Duration of First MMR Among Newly Diagnosed Patients Who Achieved MMR	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

* Complete cytogenetic response (CCyR) - 0% Ph+ metaphases * Partial cytogenetic response (PCyR) - \>0 to 35% Ph+ metaphases * Minor cytogenetic response (mCyR) - \>35 to 65% Ph+ metaphases * Minimal - \>65 to 95% Ph+ metaphases * None - \>95 to 100% Ph+ metaphases * Major cytogenetic response (MCyR) - 0 to 35% Ph+ metaphases. A major response combines both complete and partial responses.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall None	3.0 Percentage of participants	—
Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall Missing	9.1 Percentage of participants	—
Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall Major cytogenetic response: Complete	81.1 Percentage of participants	—
Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall Major cytogenetic response: Partial	3.0 Percentage of participants	—
Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall Minimal	3.0 Percentage of participants	—

SECONDARY outcome

Timeframe: up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

Complete cytogenetic response (CCyR) - 0% Ph+ metaphases No response - \>95 to 100% Ph+ metaphases

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Best Complete Cytogenetic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients - Overall	84.0 Percentage of participants Interval 63.9 to 95.5	—

SECONDARY outcome

Timeframe: From first dosing to the first CCyR up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as having CCyR by 6 cycles (respectively 12 cycles) if the patient met the CCyR criteria at least once at any time between first study drug intake and cycle 6 (cycle 12 respectively) visit included.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Summary of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients	5.55 months Interval 5.49 to 5.59	—

SECONDARY outcome

Timeframe: From first dosing to the first CCyR up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as having CCyR by 6 cycles (respectively 12 cycles) if the patient met the CCyR criteria at least once at any time between first study drug intake and cycle 6 (cycle 12 respectively) visit included.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Kaplan-Meier Estimates of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients	5.6 months Interval 5.5 to 5.6	—

SECONDARY outcome

Timeframe: From CCyR to loss of CCyR up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as having CCyR by 6 cycles (respectively 12 cycles) if the patient met the CCyR criteria at least once at any time between first study drug intake and cycle 6 (cycle 12 respectively) visit included.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=21 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Kaplan-Meier Estimates of Duration of First Complete Cytogenic Response (CCyR) Among Patients Who Achieved CCyR in Newly Diagnosed Ph+ CML-CP Patients	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: 6, 12, 18, 24, 36, 48, 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Major cytogenetic response (MCyR) - 0 to 35% Ph+ metaphases. A major response combines both complete and partial responses.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 6	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 12	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 18	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 24	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 36	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 48	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients by cycle 66	88.0 Percentage of participants Interval 68.8 to 97.5	—

SECONDARY outcome

Timeframe: up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Major cytogenetic response (MCyR) - 0 to 35% Ph+ metaphases. A major response combines both complete and partial responses.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=22 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Summary of Time to First Major Cytogenetic Response (MCyR) Among Patients Who Achieved MCyR in Newly Diagnosed CML-CP Patients	5.55 months Interval 5.52 to 5.59	—

SECONDARY outcome

Timeframe: up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Major cytogenetic response (MCyR) - 0 to 35% Ph+ metaphases. A major response combines both complete and partial responses.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Kaplan-Meier Estimates of Time to First Major Cytogenetic Response (MCyR) in Newly Diagnosed CML-CP Patients	5.55 months Interval 5.52 to 5.59	—

SECONDARY outcome

Timeframe: cycle 3, 6, 9, 12, 18, 24, 36, 48, 66

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Complete Hematological Response (CHR) was defined as * WBC count \<10×109/L * platelet count \<450×109/L * basophils \<5% * no blasts and promyelocytes in peripheral blood * myelocytes+metamyelocytes \<5% in peripheral blood * no evidence of extramedullary disease, including spleen and liver * Assessment confirmation after at least 4 weeks for newly diagnosed Ph+ CML-CP

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Best Complete Hematological Response (CHR) by Time Point by cycle 3	76.0 Percentage of participants Interval 54.9 to 90.6	—
Best Complete Hematological Response (CHR) by Time Point by cycle 6	84.0 Percentage of participants Interval 63.9 to 95.5	—
Best Complete Hematological Response (CHR) by Time Point by cycle 9	88.0 Percentage of participants Interval 68.8 to 97.5	—
Best Complete Hematological Response (CHR) by Time Point by cycle 12	92.0 Percentage of participants Interval 74.0 to 99.0	—
Best Complete Hematological Response (CHR) by Time Point by cycle 18	92.0 Percentage of participants Interval 74.0 to 99.0	—
Best Complete Hematological Response (CHR) by Time Point by cycle 24	92.0 Percentage of participants Interval 74.0 to 99.0	—
Best Complete Hematological Response (CHR) by Time Point by cycle 36	92.0 Percentage of participants Interval 74.0 to 99.0	—
Best Complete Hematological Response (CHR) by Time Point by cycle 48	92.0 Percentage of participants Interval 74.0 to 99.0	—
Best Complete Hematological Response (CHR) by Time Point by cycle 66	92.0 Percentage of participants Interval 74.0 to 99.0	—

SECONDARY outcome

Timeframe: from first dosing to CHR, UP TO 66 CYCLES

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=23 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Summary of Time to First Complete Hematological Response (CHR) Among Patients Who Achieved Confirmed CHR in Newly Diagnosed CML-CP Patients	0.95 months Interval 0.72 to 2.76	—

SECONDARY outcome

Timeframe: from first dosing to CHR, UP TO 66 CYCLES

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Kaplan-Meier Estimates of Time to First Complete Hematological Response (CHR) in Newly Diagnosed CML-CP Patients	1.0 months Interval 1.0 to 2.8	—

SECONDARY outcome

Timeframe: From first dosing to the disease progression within 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Time to disease progression is the time from the date of first study drug intake to the date of event defined as the first progression to AP or BC (from CP) or to BC (from AP) or the date of CML-related death occurring on treatment, whichever was earlier.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Time to Disease Progression for Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients - Kaplan-Meier Estimates	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: From first dosing to the disease progression or death up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Event Free Survival is defined as the time from the date of first study drug intake to the first occurrence of any of the following loss of CHR, loss of MCyR ( PCyR + CCyR), progression to AP/BC (from CP) or to BC (from AP), or death from any cause. (Including events only during treatment)

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Event Free Survival in Imatinib/Dasatinib Resistant/Intolerant CML-CP Patients	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: From first dosing to the disease progression or death up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Event Free Survival in Newly Diagnosed CML-CP Patients	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: from first dosing to death up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Overall survival is defined as the time from the date of first study drug intake to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of their last assessment for patients on study and date of last contact for patients in follow-up.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Overall Survival (OS) in Imatinib/Dasatinib Resistant/Intolerant CML-CP - Kaplan-Meier Estimates	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: from first dosing to death up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Overall Survival (OS) in Newly Diagnosed CML-CP Patients	NA months NA = not estimable as there were not enough events	—

SECONDARY outcome

Timeframe: By 3, 6, 9, 12, 18, 24, 36, 48, 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication.

BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. BCR-ABL transcript levels were summarized by cohort and time point. MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP n=25 Participants Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 3	36.4 Percentage of participants Interval 20.4 to 54.9	12.0 Percentage of participants Interval 2.5 to 31.2
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 6	45.5 Percentage of participants Interval 28.1 to 63.6	52.0 Percentage of participants Interval 31.3 to 72.2
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 9	51.5 Percentage of participants Interval 33.5 to 69.2	56.0 Percentage of participants Interval 34.9 to 75.6
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 12	57.6 Percentage of participants Interval 39.2 to 74.5	64.0 Percentage of participants Interval 42.5 to 82.0
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 18	57.6 Percentage of participants Interval 39.2 to 74.5	68.0 Percentage of participants Interval 46.5 to 85.1
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 24	57.6 Percentage of participants Interval 39.2 to 74.5	68.0 Percentage of participants Interval 46.5 to 85.1
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 36	57.6 Percentage of participants Interval 39.2 to 74.5	76.0 Percentage of participants Interval 54.9 to 90.6
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 48	60.6 Percentage of participants Interval 42.1 to 77.1	76.0 Percentage of participants Interval 54.9 to 90.6
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle By Cycle 66	60.6 Percentage of participants Interval 42.1 to 77.1	76.0 Percentage of participants Interval 54.9 to 90.6

SECONDARY outcome

Timeframe: Cycle 1 Day 8

Population: Pharmacokinetics Analysis Set (PAS): All patients with at least one evaluable PK blood sample. Of the 32 patients included in the PAS, only 30 had evaluable Ctrough.

PK was analyzed only when all patients has completed 12 cycles on treatment or discontinued the study treatment early.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=30 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Pharmacokinetics (PK): Steady State Concentration of Nilotinib in Imatinib/Dasatinib Resistant/Intolerant CML-CP Patients	1407.89 ng/mL Geometric Coefficient of Variation 41.67	—

SECONDARY outcome

Timeframe: Cycle 1 Day 8

Population: Pharmacokinetics Analysis Set (PAS): All patients with at least one evaluable PK blood sample.

PK was analyzed only when all patients has completed 12 cycles of treatment or discontinued the study treatment early.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=25 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Pharmacokinetics: Steady State Concentration of Nilotinib in Newly Diagnosed CML-CP Patients	1274.30 ng/mL Geometric Coefficient of Variation 46.21	—

SECONDARY outcome

Timeframe: from first dosing to 66 cycles

Population: Safety Set (SAF): All patients who received at least one dose of study medication in participants with both a baseline and post-baseline value.

To assess long term effect on growth, development and maturation of nilotinib treatment in pediatric patients with Ph+ CML in participants with both a baseline and post-baseline value.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP n=25 Participants Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Growth Data: Abnormal Height Standard Deviation Scores (SDS) Changes by Cohort Decrease from baseline of 1 SDS category (n=32,24)	27.3 Percentage of participants	32.0 Percentage of participants
Growth Data: Abnormal Height Standard Deviation Scores (SDS) Changes by Cohort Decrease from baseline of 2 SDS categories (n=32, 24)	3.0 Percentage of participants	16.0 Percentage of participants
Growth Data: Abnormal Height Standard Deviation Scores (SDS) Changes by Cohort Decrease from baseline of 3 SDS categories(n= 32, 24)	6.1 Percentage of participants	4.0 Percentage of participants

SECONDARY outcome

Timeframe: up to Cycle 12

Population: Safety Set (SAF): All patients who received at least one dose of study medication.

Acceptability of the study drug was evaluated from a questionnaire completed by patients, with the help from parents or caregivers at visits. The Questionnaire to capture patient assessment of palatability (very good to very bad) and acceptability of taking the medication (very easy to very hard to administration).

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=58 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation Cycle (C) 1 Day (D) 1: Completed questionnaire - Patients	75.9 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Completed questionnaire - Parents/Caregivers	22.4 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Patients who swallowed capsule whole	91.4 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Patients had capsule mixed with apple sauce	6.9 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Patients who reported no taste/unable to answer question	43.1 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Patients who reported taste as good/very good	12.1 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Patients who reported taste as not good/not bad	34.5 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D1: Reported capsule to be very easy/easy to administer	79.3 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D28: Completed questionnaire - Patients	55.2 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C1D28: Completed questionnaire - Parents/Caregivers	22.4 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C12D28: Completed questionnaire - Patients	55.2 Percentage of participants	—
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation C12D28: Completed questionnaire - Parents/Caregivers	22.4 Percentage of participants	—

SECONDARY outcome

Timeframe: up to 66 cycles

Population: Full Analysis Set (FAS): All patients who received at least one dose of study medication

Emerging signs of resistance to nilotinib

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP n=25 Participants Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Mutational Assessment of BCR-ABL Patients with >=1 evaluable post-baseline mutational analysis	39.4 Percentage of participants	32.0 Percentage of participants
Mutational Assessment of BCR-ABL Patients with any emergent mutation on treatment	0.0 Percentage of participants	0.0 Percentage of participants
Mutational Assessment of BCR-ABL Patients with multiple emergent mutations on treatment	0.0 Percentage of participants	0.0 Percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle 66

Population: Safety Set (SAF): All patients who received at least one dose of study medication.

The summary of bone age and Dual-energy X-ray absorptiometry (DEXA) by cohort. Alteration of bone biochemical markers of hand and wrist X-Ray evaluation was observed in bone age standard deviation scores (SDS) and for bone mineral density for DEXA before and after treatment with nilotinib.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP n=25 Participants Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
Long Term Effect of Nilotinib on Bone Metabolism X-ray (n= 6, 0)	-0.61 Percentage of participants Standard Deviation 1.703	—
Long Term Effect of Nilotinib on Bone Metabolism DEXA (n = 14, 10)	-0.35 Percentage of participants Standard Deviation 1.243	-0.70 Percentage of participants Standard Deviation 1.043

POST_HOC outcome

Timeframe: approx. 64.5 months, approx. 7 years

Population: Clinical Database Population: All treated participants.

On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 64.5 months (treatment duration ranged from 0.7 to 63.5 months). Deaths post treatment survival follow up were collected after the on- treatment period, up to approx. 7 years.

Outcome measures

Outcome measures
Measure	Resistant/Intolerant Ph+ CML in CP n=33 Participants Patients resistant or intolerant to either imatinib or dasatinib	Newly Diagnosed and Untreated Ph+ CML in First CP n=25 Participants Patients newly diagnosed in Chronic phase. Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
All Collected Deaths On-treatment deaths	0 Participants	0 Participants
All Collected Deaths Total Deaths	1 Participants	3 Participants

Adverse Events

Resistant/Intolerant Ph+ CML in CP

Serious events: 11 serious events

Other events: 33 other events

Deaths: 0 deaths

Newly Diagnosed and Untreated Ph+ CML in First CP

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

All Patients

Serious events: 15 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

NovartisPharmaceuticals

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER