Trial Outcomes & Findings for Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome & /or BCR-ABL Positive Chronic Myeloid Leukaemia in Chronic Phase (NCT NCT01061177)
NCT ID: NCT01061177
Last Updated: 2017-02-24
Results Overview
MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
COMPLETED
PHASE4
1090 participants
at 18 months
2017-02-24
Participant Flow
ITT: intent to treat; b3a2 \& b2a2 +ve are categories of BCR-ABL transcripts (BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia and acute lymphoblastic leukemia patients; CyR (Ph+ Patients Only) = cytogenic response for Philadelphia positive patients only.
Participant milestones
| Measure |
Nilotinib
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Overall Study
STARTED
|
1089
|
|
Overall Study
ITT_MR (b2a2 &/or b3a2 +ve Pts Only)
|
1056
|
|
Overall Study
ITT_CyR (Ph+ Patients Only)
|
983
|
|
Overall Study
COMPLETED
|
881
|
|
Overall Study
NOT COMPLETED
|
208
|
Reasons for withdrawal
| Measure |
Nilotinib
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Overall Study
Adverse Event
|
117
|
|
Overall Study
Withdrawal by Subject
|
27
|
|
Overall Study
Disease progression
|
17
|
|
Overall Study
Protocol Violation
|
11
|
|
Overall Study
Lost to Follow-up
|
9
|
|
Overall Study
New cancer therapy
|
9
|
|
Overall Study
Abnormal laboratory values
|
6
|
|
Overall Study
Abnormal test procedure results
|
4
|
|
Overall Study
Administratie problems
|
4
|
|
Overall Study
Death
|
4
|
Baseline Characteristics
Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome & /or BCR-ABL Positive Chronic Myeloid Leukaemia in Chronic Phase
Baseline characteristics by cohort
| Measure |
Nilotinib
n=1089 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Age, Continuous
|
51.6 Years
STANDARD_DEVIATION 14.87 • n=5 Participants
|
|
Gender
Female
|
447 Participants
n=5 Participants
|
|
Gender
Male
|
642 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucacian
|
1045 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Oriental
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native American
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
31 Participants
n=5 Participants
|
|
Weight at baseline
|
77.47 Kg
STANDARD_DEVIATION 15.730 • n=5 Participants
|
|
ECOG performance score
No restrictions (0)
|
867 Participants
n=5 Participants
|
|
ECOG performance score
Only light work (1)
|
199 Participants
n=5 Participants
|
|
ECOG performance score
Only self care (2)
|
21 Participants
n=5 Participants
|
|
ECOG performance score
Limited self care (3)
|
0 Participants
n=5 Participants
|
|
ECOG performance score
Completely disabled (4)
|
0 Participants
n=5 Participants
|
|
ECOG performance score
Missing
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: at 18 monthsPopulation: Intent-to-treat\_Molecular (ITT\_MR) analysis set was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening.
MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
Outcome measures
| Measure |
Nilotinib
n=1056 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Molecular Response (MR4^0) at 18 Months
|
38.3 Percentage of Participants
|
SECONDARY outcome
Timeframe: at 12 and 24 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but \< 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (\< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.
Outcome measures
| Measure |
Nilotinib
n=1089 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants Free From Progression to Accelerated Phase/Blast Crisis (AP/BC) at 12 and 24 Months
Pts free from progression to AP/BC at 12 months
|
99.4 Percentage of participants
|
|
Percentage of Participants Free From Progression to Accelerated Phase/Blast Crisis (AP/BC) at 12 and 24 Months
Pts free from progression to AP/BC at 24 months
|
99.4 Percentage of participants
|
SECONDARY outcome
Timeframe: at 12 and 24 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (ie, 91 + 15 days), Not achieving CCyR up to 18 months (ie, 548 + 15 days), whichever is earlier.
Outcome measures
| Measure |
Nilotinib
n=1089 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Rate of Event Free Survival at 12 and 24 Months
Percentage of participants with EFS at 12 months
|
71.7 Percentage of participants
|
|
Rate of Event Free Survival at 12 and 24 Months
Percentage of participants with EFS at 24 months
|
69.1 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 months, 24 monthsPopulation: Intent-to-treat\_Molecular (ITT\_MR) analysis set was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening.
MMR was defined as BCR-ABL ratio (IS) ≤ 0.1% in a peripheral blood sample. BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR ("breakpoint cluster region") gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins.
Outcome measures
| Measure |
Nilotinib
n=1056 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months
at 12 months
|
56.2 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months
at 24 months
|
61.1 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months
by 12 months
|
68.8 Percentage of participants
|
|
Percentage of Participants With Major Molecular Response (MMR) at, as Well as by, 12 and 24 Months
by 24 months
|
80.3 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 and 24 monthsPopulation: The ITT\_CyR population was a subset of the ITT population including the Ph+ patients at screening was considered. Patients who had either no metaphases recorded at screening bone marrow or only negative metaphases recorded at screening bone marrow but had Ph+ metaphases at any visits after screening were also part of this population.
CCyR parameters were defined as 0% Philadelphia positive (Ph+) metaphases. Loss of CCyR was defined as a patient exceeding the CCyR criteria (ie, \> 0% Ph+ metaphases) at a subsequent visit after the patient had achieved CCyR.
Outcome measures
| Measure |
Nilotinib
n=983 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months
at 12 months
|
72.4 Percentage of participants
|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months
at 24 months
|
65.6 Percentage of participants
|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months
By Month 12
|
82.5 Percentage of participants
|
|
Percentage of Participants With Complete Cytogenetic Response (CCyR) at, as Well as by, 12 and 24 Months
By Month 24
|
89.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 and 24 monthsPopulation: The ITT\_CyR population was a subset of the ITT population including the Ph+ patients at screening was considered. Patients who had either no metaphases recorded at screening bone marrow or only negative metaphases recorded at screening bone marrow but had Ph+ metaphases at any visits after screening were also part of this population.
Major cytogenetic response (MCyR) parameters were defined as 0 to 35% Philadelphia positive (Ph+) metaphases.
Outcome measures
| Measure |
Nilotinib
n=983 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months
at 12 months
|
73.8 Percentage of participants
|
|
Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months
at 24 months
|
66.2 Percentage of participants
|
|
Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months
by 12 months
|
86.7 Percentage of participants
|
|
Percentage of Participants With Major Cytogenetic Response (MCyR) at, as Well as by, 12 and 24 Months
by 24 months
|
91.4 Percentage of participants
|
SECONDARY outcome
Timeframe: at 12 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but \< 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (\< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.
Outcome measures
| Measure |
Nilotinib
n=400 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants Free From Progression to AP/BC With MR4^0 at 12 Months
|
100.0 Percentage of participants
|
SECONDARY outcome
Timeframe: at 12 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (i.e. 91 + 15 days).
Outcome measures
| Measure |
Nilotinib
n=400 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Event Free Survival in Participants Achieving MR4^0 at 12 Months
|
87.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 months, 24 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
Outcome measures
| Measure |
Nilotinib
n=1089 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Progression Free Survival (PFS) at 12 and 24 Months
at 12 months
|
99.2 Percentage of participants
|
|
Percentage of Participants With Progression Free Survival (PFS) at 12 and 24 Months
at 24 months
|
99.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 and 24 monthsPopulation: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered. This population was referred to as ITT\_MR.
MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.
Outcome measures
| Measure |
Nilotinib
n=1056 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months
at 12 months
|
30.7 Percentage of participants
|
|
Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months
at 24 months
|
40.2 Percentage of participants
|
|
Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months
by month 12
|
36.9 Percentage of participants
|
|
Rate of Molecular Response (MR4^0) at, as Well as by, 12 and 24 Months
by month 24
|
55.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 and 24 monthsPopulation: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered.
MR4\^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts).
Outcome measures
| Measure |
Nilotinib
n=1056 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months
at 12 months
|
15.2 Percentage of participants
|
|
Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months
at 24 months
|
21.9 Percentage of participants
|
|
Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months
by 12 months
|
20.6 Percentage of participants
|
|
Rate of Molecular Response (MR4^5) at, as Well as by, 12 and 24 Months
by 24 months
|
38.4 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 months, 24 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
CHR was defined as all of the following present for ≥ 4 weeks in the peripheral blood: WBC count \< 10 x 109/L, Platelet count \< 450 x 109/L, No circulating peripheral blood blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood, The presence of \< 5% basophils, No evidence of disease-related symptoms and extramedullary disease, including spleen and liver. Loss of CHR was defined as the appearance of any of the following after having achieved a CHR confirmed by a second determination ≥ 4 weeks later (unless associated with progression to AP/BC or death, which was considered to be a confirmed loss of CHR event on its own): WBC count that increased to \> 20.0 x 109/L, Platelet count that increased to ≥ 600 x 109/L, Any palpable spleen, defined as size of spleen below costal margin \> 5 cm, Appearance of \> 5% myelocytes plus metamyelocytes, or any promyelocytes or blasts in the peripheral blood.
Outcome measures
| Measure |
Nilotinib
n=1089 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months
by Month 24
|
89.1 Percentage of prticipants
|
|
Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months
at 12 months
|
82.7 Percentage of prticipants
|
|
Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months
at 24 months
|
75.5 Percentage of prticipants
|
|
Rate of Complete Hematologic Response (CHR) at, as Well as by, 12 and 24 Months
by Month12
|
86.2 Percentage of prticipants
|
SECONDARY outcome
Timeframe: 12 months, 24 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
OS was defined as the time between the date of Day 1 (first treatment) and the date of death from any cause. Deaths which occurred after the 24-month time window and which were occasionally reported by some Investigators were excluded from the analysis. This is in agreement with the protocol stating that patients were to be followed for survival and progression to AP/BC up to 24 months after the participants treatment start.
Outcome measures
| Measure |
Nilotinib
n=1089 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Overall Survival at 12 and 24 Months
at 12 months
|
99.6 Percentage of participants
|
|
Percentage of Participants With Overall Survival at 12 and 24 Months
at 24 months
|
98.9 Percentage of participants
|
SECONDARY outcome
Timeframe: by 18 monthsPopulation: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered. This population was referred to as ITT\_MR.
MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts. BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase
Outcome measures
| Measure |
Nilotinib
n=1056 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Rate of Molecular Response (MR4^0) by 18 Months
|
48.5 Percentage of participants
|
SECONDARY outcome
Timeframe: by 18 monthsPopulation: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered.
MR4\^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts). BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase
Outcome measures
| Measure |
Nilotinib
n=1056 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Rate of Molecular Response (MR4^5) by 18 Months
|
31.6 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.
PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.
Outcome measures
| Measure |
Nilotinib
n=400 Participants
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Percentage of Participants With Progression Free Survival in Participants Achieving MR4^0 at 12 Months
at 12 months
|
99.2 Percentage of participants
|
|
Percentage of Participants With Progression Free Survival in Participants Achieving MR4^0 at 12 Months
at 24 months
|
99.0 Percentage of participants
|
Adverse Events
Nilotinib
Serious adverse events
| Measure |
Nilotinib
n=1089 participants at risk
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.46%
5/1089
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
0.09%
1/1089
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.09%
1/1089
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.09%
1/1089
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.18%
2/1089
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.09%
1/1089
|
|
Blood and lymphatic system disorders
Splenic infarction
|
0.09%
1/1089
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.28%
3/1089
|
|
Cardiac disorders
Acute coronary syndrome
|
0.28%
3/1089
|
|
Cardiac disorders
Acute myocardial infarction
|
0.37%
4/1089
|
|
Cardiac disorders
Angina pectoris
|
0.55%
6/1089
|
|
Cardiac disorders
Angina unstable
|
0.18%
2/1089
|
|
Cardiac disorders
Aortic valve stenosis
|
0.09%
1/1089
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.18%
2/1089
|
|
Cardiac disorders
Atrial fibrillation
|
1.2%
13/1089
|
|
Cardiac disorders
Atrial flutter
|
0.18%
2/1089
|
|
Cardiac disorders
Cardiac failure
|
0.09%
1/1089
|
|
Cardiac disorders
Cardiac failure congestive
|
0.28%
3/1089
|
|
Cardiac disorders
Coronary artery disease
|
0.64%
7/1089
|
|
Cardiac disorders
Coronary artery stenosis
|
0.09%
1/1089
|
|
Cardiac disorders
Coronary artery thrombosis
|
0.09%
1/1089
|
|
Cardiac disorders
Mitral valve disease
|
0.09%
1/1089
|
|
Cardiac disorders
Mitral valve incompetence
|
0.09%
1/1089
|
|
Cardiac disorders
Myocardial infarction
|
0.37%
4/1089
|
|
Cardiac disorders
Myocardial ischaemia
|
0.28%
3/1089
|
|
Cardiac disorders
Pericardial effusion
|
0.09%
1/1089
|
|
Cardiac disorders
Pericarditis
|
0.09%
1/1089
|
|
Cardiac disorders
Prinzmetal angina
|
0.09%
1/1089
|
|
Cardiac disorders
Sick sinus syndrome
|
0.09%
1/1089
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.09%
1/1089
|
|
Congenital, familial and genetic disorders
Atrial septal defect
|
0.09%
1/1089
|
|
Ear and labyrinth disorders
Deafness
|
0.09%
1/1089
|
|
Ear and labyrinth disorders
Vertigo
|
0.09%
1/1089
|
|
Endocrine disorders
Goitre
|
0.09%
1/1089
|
|
Endocrine disorders
Hyperthyroidism
|
0.09%
1/1089
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
0.09%
1/1089
|
|
Endocrine disorders
Thyroiditis subacute
|
0.09%
1/1089
|
|
Eye disorders
Conjunctival disorder
|
0.09%
1/1089
|
|
Eye disorders
Diabetic retinopathy
|
0.09%
1/1089
|
|
Eye disorders
Eye haemorrhage
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Abdominal pain
|
0.37%
4/1089
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.18%
2/1089
|
|
Gastrointestinal disorders
Colitis
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Constipation
|
0.28%
3/1089
|
|
Gastrointestinal disorders
Diarrhoea
|
0.18%
2/1089
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Dysphagia
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Gastric ulcer perforation
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Gastritis
|
0.18%
2/1089
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Gastrooesophageal sphincter insufficiency
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.18%
2/1089
|
|
Gastrointestinal disorders
Haemorrhoids thrombosed
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Ileus
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.18%
2/1089
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Nausea
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Pancreatic disorder
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Pancreatitis
|
0.55%
6/1089
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.18%
2/1089
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.09%
1/1089
|
|
Gastrointestinal disorders
Vomiting
|
0.46%
5/1089
|
|
General disorders
Chest pain
|
0.09%
1/1089
|
|
General disorders
Device dislocation
|
0.09%
1/1089
|
|
General disorders
Drug resistance
|
0.09%
1/1089
|
|
General disorders
Fatigue
|
0.18%
2/1089
|
|
General disorders
Localised oedema
|
0.09%
1/1089
|
|
General disorders
Non-cardiac chest pain
|
0.37%
4/1089
|
|
General disorders
Oedema peripheral
|
0.09%
1/1089
|
|
General disorders
Pyrexia
|
0.55%
6/1089
|
|
General disorders
Soft tissue inflammation
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Cholangitis
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Cholecystitis
|
0.18%
2/1089
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Gallbladder enlargement
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Hepatic fibrosis
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Hepatic steatosis
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.09%
1/1089
|
|
Hepatobiliary disorders
Jaundice
|
0.09%
1/1089
|
|
Immune system disorders
Drug hypersensitivity
|
0.09%
1/1089
|
|
Infections and infestations
Abdominal abscess
|
0.09%
1/1089
|
|
Infections and infestations
Appendicitis
|
0.09%
1/1089
|
|
Infections and infestations
Bronchitis
|
0.18%
2/1089
|
|
Infections and infestations
Bronchopneumonia
|
0.09%
1/1089
|
|
Infections and infestations
Corneal abscess
|
0.09%
1/1089
|
|
Infections and infestations
Diverticulitis
|
0.09%
1/1089
|
|
Infections and infestations
Epididymitis
|
0.09%
1/1089
|
|
Infections and infestations
Gangrene
|
0.09%
1/1089
|
|
Infections and infestations
Infection
|
0.09%
1/1089
|
|
Infections and infestations
Lung infection
|
0.09%
1/1089
|
|
Infections and infestations
Perirectal abscess
|
0.09%
1/1089
|
|
Infections and infestations
Phlebitis infective
|
0.09%
1/1089
|
|
Infections and infestations
Pneumonia
|
0.37%
4/1089
|
|
Infections and infestations
Rectal abscess
|
0.09%
1/1089
|
|
Infections and infestations
Respiratory tract infection
|
0.09%
1/1089
|
|
Infections and infestations
Urinary tract infection
|
0.09%
1/1089
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.09%
1/1089
|
|
Infections and infestations
Viral pericarditis
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Coronary artery restenosis
|
0.18%
2/1089
|
|
Injury, poisoning and procedural complications
Exposure via father
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Overdose
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Post procedural inflammation
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Sternal injury
|
0.09%
1/1089
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.09%
1/1089
|
|
Investigations
Amylase increased
|
0.18%
2/1089
|
|
Investigations
Blood creatine phosphokinase increased
|
0.18%
2/1089
|
|
Investigations
Blood pressure increased
|
0.09%
1/1089
|
|
Investigations
C-reactive protein increased
|
0.09%
1/1089
|
|
Investigations
Electrocardiogram QT prolonged
|
0.28%
3/1089
|
|
Investigations
Lipase increased
|
0.09%
1/1089
|
|
Investigations
Platelet count decreased
|
0.28%
3/1089
|
|
Investigations
Transaminases increased
|
0.09%
1/1089
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.18%
2/1089
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.28%
3/1089
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.09%
1/1089
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.09%
1/1089
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.09%
1/1089
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.18%
2/1089
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.09%
1/1089
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.09%
1/1089
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.18%
2/1089
|
|
Musculoskeletal and connective tissue disorders
Arthropathy
|
0.09%
1/1089
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.46%
5/1089
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.09%
1/1089
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.18%
2/1089
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.09%
1/1089
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.28%
3/1089
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.09%
1/1089
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.18%
2/1089
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Blast cell crisis
|
0.18%
2/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Duodenal neoplasm
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.18%
2/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Retroperitoneal cancer
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer
|
0.18%
2/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Urinary bladder adenoma
|
0.09%
1/1089
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.09%
1/1089
|
|
Nervous system disorders
Aphasia
|
0.09%
1/1089
|
|
Nervous system disorders
Carotid artery occlusion
|
0.09%
1/1089
|
|
Nervous system disorders
Carotid artery stenosis
|
0.09%
1/1089
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.09%
1/1089
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.09%
1/1089
|
|
Nervous system disorders
Cerebral ischaemia
|
0.09%
1/1089
|
|
Nervous system disorders
Cerebrovascular accident
|
0.18%
2/1089
|
|
Nervous system disorders
Cranial nerve disorder
|
0.09%
1/1089
|
|
Nervous system disorders
Facial paresis
|
0.09%
1/1089
|
|
Nervous system disorders
Headache
|
0.46%
5/1089
|
|
Nervous system disorders
Hyperaesthesia
|
0.09%
1/1089
|
|
Nervous system disorders
Intracranial aneurysm
|
0.09%
1/1089
|
|
Nervous system disorders
Ischaemic stroke
|
0.18%
2/1089
|
|
Nervous system disorders
Lethargy
|
0.09%
1/1089
|
|
Nervous system disorders
Memory impairment
|
0.09%
1/1089
|
|
Nervous system disorders
Motor neurone disease
|
0.09%
1/1089
|
|
Nervous system disorders
Neuropathy peripheral
|
0.09%
1/1089
|
|
Nervous system disorders
Occipital neuralgia
|
0.09%
1/1089
|
|
Nervous system disorders
Sciatica
|
0.09%
1/1089
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.09%
1/1089
|
|
Nervous system disorders
Transient ischaemic attack
|
0.18%
2/1089
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.09%
1/1089
|
|
Psychiatric disorders
Anxiety
|
0.09%
1/1089
|
|
Psychiatric disorders
Bipolar disorder
|
0.09%
1/1089
|
|
Psychiatric disorders
Confusional state
|
0.09%
1/1089
|
|
Psychiatric disorders
Depression
|
0.37%
4/1089
|
|
Psychiatric disorders
Depression suicidal
|
0.09%
1/1089
|
|
Psychiatric disorders
Suicide attempt
|
0.28%
3/1089
|
|
Renal and urinary disorders
Dysuria
|
0.09%
1/1089
|
|
Renal and urinary disorders
Haematuria
|
0.09%
1/1089
|
|
Renal and urinary disorders
Incontinence
|
0.09%
1/1089
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.18%
2/1089
|
|
Renal and urinary disorders
Renal colic
|
0.09%
1/1089
|
|
Renal and urinary disorders
Renal cyst
|
0.09%
1/1089
|
|
Renal and urinary disorders
Renal failure
|
0.09%
1/1089
|
|
Renal and urinary disorders
Renal failure acute
|
0.18%
2/1089
|
|
Renal and urinary disorders
Renal impairment
|
0.09%
1/1089
|
|
Renal and urinary disorders
Urinary retention
|
0.09%
1/1089
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.09%
1/1089
|
|
Reproductive system and breast disorders
Genital pain
|
0.09%
1/1089
|
|
Reproductive system and breast disorders
Genital swelling
|
0.09%
1/1089
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.09%
1/1089
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.18%
2/1089
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.46%
5/1089
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.18%
2/1089
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
0.09%
1/1089
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.09%
1/1089
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.09%
1/1089
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.09%
1/1089
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.09%
1/1089
|
|
Skin and subcutaneous tissue disorders
Diabetic foot
|
0.09%
1/1089
|
|
Skin and subcutaneous tissue disorders
Dry gangrene
|
0.09%
1/1089
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.09%
1/1089
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.09%
1/1089
|
|
Surgical and medical procedures
Hysterectomy
|
0.09%
1/1089
|
|
Surgical and medical procedures
Skin neoplasm excision
|
0.09%
1/1089
|
|
Vascular disorders
Aneurysm ruptured
|
0.09%
1/1089
|
|
Vascular disorders
Aortic stenosis
|
0.18%
2/1089
|
|
Vascular disorders
Arterial disorder
|
0.09%
1/1089
|
|
Vascular disorders
Arterial haemorrhage
|
0.09%
1/1089
|
|
Vascular disorders
Arterial occlusive disease
|
0.09%
1/1089
|
|
Vascular disorders
Deep vein thrombosis
|
0.09%
1/1089
|
|
Vascular disorders
Haemorrhage
|
0.09%
1/1089
|
|
Vascular disorders
Hypertension
|
0.09%
1/1089
|
|
Vascular disorders
Hypertensive crisis
|
0.09%
1/1089
|
|
Vascular disorders
Leriche syndrome
|
0.09%
1/1089
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.18%
2/1089
|
|
Vascular disorders
Peripheral artery stenosis
|
0.09%
1/1089
|
|
Vascular disorders
Peripheral ischaemia
|
0.09%
1/1089
|
|
Vascular disorders
Raynaud's phenomenon
|
0.09%
1/1089
|
Other adverse events
| Measure |
Nilotinib
n=1089 participants at risk
This was a single-arm study; therefore all participants received nilotinib (AMN107) 300 mg bid given as two 150 mg capsules twice daily.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.0%
65/1089
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.2%
111/1089
|
|
Gastrointestinal disorders
Abdominal pain
|
7.3%
79/1089
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.1%
88/1089
|
|
Gastrointestinal disorders
Constipation
|
6.0%
65/1089
|
|
Gastrointestinal disorders
Diarrhoea
|
8.5%
93/1089
|
|
Gastrointestinal disorders
Nausea
|
11.2%
122/1089
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
62/1089
|
|
General disorders
Asthenia
|
8.9%
97/1089
|
|
General disorders
Fatigue
|
13.8%
150/1089
|
|
Infections and infestations
Nasopharyngitis
|
10.4%
113/1089
|
|
Investigations
Alanine aminotransferase increased
|
7.9%
86/1089
|
|
Investigations
Blood bilirubin increased
|
7.3%
80/1089
|
|
Investigations
Lipase increased
|
7.0%
76/1089
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.1%
77/1089
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.8%
96/1089
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.2%
78/1089
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.5%
93/1089
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
99/1089
|
|
Nervous system disorders
Headache
|
15.0%
163/1089
|
|
Psychiatric disorders
Insomnia
|
5.1%
55/1089
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
56/1089
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.6%
115/1089
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.5%
93/1089
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.5%
180/1089
|
|
Skin and subcutaneous tissue disorders
Rash
|
21.4%
233/1089
|
|
Vascular disorders
Hypertension
|
5.9%
64/1089
|
Additional Information
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 (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER