Trial Outcomes & Findings for Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients (NCT NCT01254188)
NCT ID: NCT01254188
Last Updated: 2016-03-03
Results Overview
MMR is defined as BCR-ABL ratio (%) on IS \<= 0.1% (corresponds to \>=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
421 participants
Primary outcome timeframe
12 months
Results posted on
2016-03-03
Participant Flow
Participant milestones
| Measure |
Nilotinib
Nilotinib 300 mg BID
|
|---|---|
|
Overall Study
STARTED
|
421
|
|
Overall Study
COMPLETED
|
328
|
|
Overall Study
NOT COMPLETED
|
93
|
Reasons for withdrawal
| Measure |
Nilotinib
Nilotinib 300 mg BID
|
|---|---|
|
Overall Study
Disease Progression
|
6
|
|
Overall Study
Protocol Violation
|
6
|
|
Overall Study
Pregnancy
|
2
|
|
Overall Study
Death
|
4
|
|
Overall Study
Lost to Follow-up
|
5
|
|
Overall Study
Withdrawal by Subject
|
7
|
|
Overall Study
Adverse Event
|
43
|
|
Overall Study
per investigator discretion
|
20
|
Baseline Characteristics
Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients
Baseline characteristics by cohort
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
368 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
53 Participants
n=5 Participants
|
|
Age, Continuous
|
47.13 years
STANDARD_DEVIATION 14.892 • n=5 Participants
|
|
Sex: Female, Male
Female
|
195 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
226 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsMMR is defined as BCR-ABL ratio (%) on IS \<= 0.1% (corresponds to \>=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
The Percentage of Patients Achieving MMR by 12 Months
|
70.8 percentage of participants
Interval 66.1 to 75.2
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: Full analysis set
Estimated median time to first MMR by Kaplan-Meier method
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Time to Molecular Response at 24 Months
|
6.0 Months
Interval 5.9 to 6.1
|
SECONDARY outcome
Timeframe: 3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detectedPopulation: Full Analysis set, Number of events / censored 29/312.
Kaplan-Meier estimates of duration of first MMR among patients who achieved MMR (FAS) Duration of first MMR (months) = (Minimum date of (loss of first MMR , CML-related death, progression to AP/BC during study treatment, censoring) - date of first MMR + 1) / 30.4375
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Duration of Major Molecular Response
K-M Estimate for 3 Month Duration
|
100 percentage of participants
Interval 100.0 to 100.0
|
|
Duration of Major Molecular Response
K-M Estimate for 6 Month Duration
|
97.1 percentage of participants
Interval 65.2 to 99.0
|
|
Duration of Major Molecular Response
K-M Estimate for 9 Month Duration
|
92.8 percentage of participants
Interval 89.9 to 95.7
|
|
Duration of Major Molecular Response
K-M Estimate for 12 Month Duration
|
92.1 percentage of participants
Interval 89.1 to 95.1
|
|
Duration of Major Molecular Response
K-M Estimate for 15 Month Duration
|
91.7 percentage of participants
Interval 88.5 to 94.8
|
|
Duration of Major Molecular Response
18 months
|
90.8 percentage of participants
Interval 87.4 to 94.1
|
|
Duration of Major Molecular Response
K-M Estimate for 21 Month Duration
|
89.7 percentage of participants
Interval 85.7 to 93.6
|
|
Duration of Major Molecular Response
K-M Estimate for 24 Month Duration
|
85.2 percentage of participants
Interval 75.8 to 94.5
|
SECONDARY outcome
Timeframe: 6 monthsComplete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Complete Cytogenetic Response
|
58.7 percentage of participants
Interval 53.8 to 63.4
|
SECONDARY outcome
Timeframe: 6,12,18 and 24 months\* CCyR = 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Duration of first CCyR (months) = (date of CCyR loss or censoring - date of first CCyR +1) / 30.4375
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.
6 mos after the first CCyR was achieved
|
100 percentage of participants
Interval 100.0 to 100.0
|
|
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.
12 mos after the first CCyR was achieved
|
99.6 percentage of participants
Interval 98.8 to 100.0
|
|
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.
18 mos after the first CCyR was achieved
|
98.7 percentage of participants
Interval 97.1 to 100.0
|
|
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.
24 mos after the first CCyR was achieved
|
98.7 percentage of participants
Interval 97.1 to 100.0
|
SECONDARY outcome
Timeframe: 3, 6, 9, 12, 15, 18, 21, 24 MonthsOS was defined as the time between date of study entry and date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Overall Survival
3 months K-M Estimate
|
99.8 percentage probability
Interval 99.3 to 100.0
|
|
Overall Survival
6 months K-M Estimate
|
99.5 percentage probability
Interval 98.9 to 100.0
|
|
Overall Survival
9 months K-M Estimate
|
99.5 percentage probability
Interval 98.9 to 100.0
|
|
Overall Survival
12 months K-M Estimate
|
99.0 percentage probability
Interval 98.0 to 100.0
|
|
Overall Survival
15 months K-M Estimate
|
98.2 percentage probability
Interval 96.9 to 99.5
|
|
Overall Survival
18 months K-M Estimate
|
97.6 percentage probability
Interval 96.1 to 99.2
|
|
Overall Survival
21 months K-M Estimate
|
97.6 percentage probability
Interval 96.1 to 99.2
|
|
Overall Survival
24 months K-M Estimate
|
97.6 percentage probability
Interval 96.1 to 99.2
|
SECONDARY outcome
Timeframe: 3,6,9,12,15,18,21,and 24 monthsPopulation: FAS
PFS was defined as the time from the date of study entry to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring on treatment.
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Kaplan-Meier Estimates of Progression-free Survival
3 mos
|
99.7 percentage probability
Interval 99.3 to 100.0
|
|
Kaplan-Meier Estimates of Progression-free Survival
6 mos
|
99.5 percentage probability
Interval 98.8 to 100.0
|
|
Kaplan-Meier Estimates of Progression-free Survival
9 mos
|
98.9 percentage probability
Interval 97.8 to 100.0
|
|
Kaplan-Meier Estimates of Progression-free Survival
12 mos
|
98.6 percentage probability
Interval 97.4 to 99.8
|
|
Kaplan-Meier Estimates of Progression-free Survival
15 mos
|
98.0 percentage probability
Interval 96.5 to 99.5
|
|
Kaplan-Meier Estimates of Progression-free Survival
18 mos
|
97.6 percentage probability
Interval 96.0 to 99.3
|
|
Kaplan-Meier Estimates of Progression-free Survival
21 mos
|
97.6 percentage probability
Interval 96.0 to 99.3
|
|
Kaplan-Meier Estimates of Progression-free Survival
24 mos
|
97.0 percentage probability
Interval 95.1 to 98.8
|
SECONDARY outcome
Timeframe: 3,6,9,12,15,18,21,and 24 monthsPopulation: FAS
Time to event (months) = (date of event or censoring - date of study entry + 1) / 30.4375. Date of event is the earliest date of the following events during treatment : discontinuation of nilotinib for nilotinib-related adverse events, death due to any cause, progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR. Time is censored at the date of last assessment in the trial for patients without event.
Outcome measures
| Measure |
Nilotinib
n=421 Participants
Nilotinib 300 mg BID
|
|---|---|
|
Kaplan-Meier Estimates of Failure-free Survival
3 mos
|
97.4 percentage probability
Interval 95.8 to 98.9
|
|
Kaplan-Meier Estimates of Failure-free Survival
6 mos
|
95.9 percentage probability
Interval 93.9 to 97.8
|
|
Kaplan-Meier Estimates of Failure-free Survival
9 mos
|
94.6 percentage probability
Interval 92.4 to 96.8
|
|
Kaplan-Meier Estimates of Failure-free Survival
12 mos
|
93.6 percentage probability
Interval 91.2 to 96.0
|
|
Kaplan-Meier Estimates of Failure-free Survival
15 mos
|
92.0 percentage probability
Interval 89.4 to 94.7
|
|
Kaplan-Meier Estimates of Failure-free Survival
18 mos
|
91.0 percentage probability
Interval 88.2 to 93.8
|
|
Kaplan-Meier Estimates of Failure-free Survival
21 mos
|
89.7 percentage probability
Interval 86.6 to 92.7
|
|
Kaplan-Meier Estimates of Failure-free Survival
24 mos
|
88.8 percentage probability
Interval 85.7 to 92.0
|
Adverse Events
Nilotinib
Serious events: 97 serious events
Other events: 357 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Nilotinib
n=421 participants at risk
Nilotinib 300 mg BID
|
|---|---|
|
Blood and lymphatic system disorders
AGRANULOCYTOSIS
|
0.24%
1/421
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.95%
4/421
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.95%
4/421
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
0.24%
1/421
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
0.48%
2/421
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
0.71%
3/421
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
0.48%
2/421
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
2.9%
12/421
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.48%
2/421
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.48%
2/421
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.71%
3/421
|
|
Cardiac disorders
ARRHYTHMIA
|
0.24%
1/421
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.95%
4/421
|
|
Cardiac disorders
CARDIAC ARREST
|
0.24%
1/421
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.24%
1/421
|
|
Cardiac disorders
CARDIAC TAMPONADE
|
0.24%
1/421
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.24%
1/421
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.48%
2/421
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.48%
2/421
|
|
Cardiac disorders
MYOCARDIAL ISCHAEMIA
|
0.48%
2/421
|
|
Cardiac disorders
SINUS BRADYCARDIA
|
0.24%
1/421
|
|
Endocrine disorders
HYPERTHYROIDISM
|
0.24%
1/421
|
|
Eye disorders
CATARACT
|
0.48%
2/421
|
|
Eye disorders
RETINAL VEIN OCCLUSION
|
0.24%
1/421
|
|
Eye disorders
VITREOUS HAEMORRHAGE
|
0.24%
1/421
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.24%
1/421
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.24%
1/421
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.48%
2/421
|
|
Gastrointestinal disorders
DUODENAL ULCER
|
0.24%
1/421
|
|
Gastrointestinal disorders
GASTROINTESTINAL PAIN
|
0.24%
1/421
|
|
Gastrointestinal disorders
HYPERCHLORHYDRIA
|
0.24%
1/421
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.24%
1/421
|
|
Gastrointestinal disorders
INTESTINAL INFARCTION
|
0.24%
1/421
|
|
Gastrointestinal disorders
NAUSEA
|
0.24%
1/421
|
|
Gastrointestinal disorders
PANCREATITIS
|
1.7%
7/421
|
|
Gastrointestinal disorders
PANCREATITIS ACUTE
|
0.24%
1/421
|
|
Gastrointestinal disorders
RECTAL HAEMORRHAGE
|
0.24%
1/421
|
|
Gastrointestinal disorders
VOMITING
|
0.24%
1/421
|
|
General disorders
ASTHENIA
|
0.24%
1/421
|
|
General disorders
GENERALISED OEDEMA
|
0.24%
1/421
|
|
General disorders
PAIN
|
0.24%
1/421
|
|
General disorders
PYREXIA
|
0.71%
3/421
|
|
General disorders
SUDDEN DEATH
|
0.24%
1/421
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.48%
2/421
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.24%
1/421
|
|
Hepatobiliary disorders
DRUG-INDUCED LIVER INJURY
|
0.24%
1/421
|
|
Infections and infestations
ANAL ABSCESS
|
0.24%
1/421
|
|
Infections and infestations
APPENDICITIS
|
0.24%
1/421
|
|
Infections and infestations
CELLULITIS
|
0.24%
1/421
|
|
Infections and infestations
DIARRHOEA INFECTIOUS
|
0.24%
1/421
|
|
Infections and infestations
GASTROENTERITIS
|
0.24%
1/421
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.24%
1/421
|
|
Infections and infestations
PHARYNGITIS
|
0.24%
1/421
|
|
Infections and infestations
PNEUMONIA
|
0.95%
4/421
|
|
Infections and infestations
PYELONEPHRITIS CHRONIC
|
0.24%
1/421
|
|
Infections and infestations
TRACHEOBRONCHITIS
|
0.24%
1/421
|
|
Injury, poisoning and procedural complications
LACERATION
|
0.48%
2/421
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.24%
1/421
|
|
Investigations
AMYLASE INCREASED
|
0.48%
2/421
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
0.48%
2/421
|
|
Investigations
LIPASE INCREASED
|
0.24%
1/421
|
|
Investigations
LIVER FUNCTION TEST ABNORMAL
|
0.24%
1/421
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.48%
2/421
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.24%
1/421
|
|
Metabolism and nutrition disorders
HYPERLIPASAEMIA
|
0.24%
1/421
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.24%
1/421
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.24%
1/421
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.24%
1/421
|
|
Musculoskeletal and connective tissue disorders
ROTATOR CUFF SYNDROME
|
0.24%
1/421
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA
|
0.24%
1/421
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLAST CELL CRISIS
|
0.71%
3/421
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM PROGRESSION
|
0.24%
1/421
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTATIC MALIGNANT MELANOMA
|
0.24%
1/421
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.24%
1/421
|
|
Nervous system disorders
CEREBRAL HAEMATOMA
|
0.24%
1/421
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.24%
1/421
|
|
Nervous system disorders
HAEMORRHAGIC STROKE
|
0.24%
1/421
|
|
Nervous system disorders
HEADACHE
|
0.24%
1/421
|
|
Nervous system disorders
INTRACRANIAL PRESSURE INCREASED
|
0.24%
1/421
|
|
Nervous system disorders
MYASTHENIA GRAVIS
|
0.24%
1/421
|
|
Nervous system disorders
SCIATICA
|
0.24%
1/421
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.48%
2/421
|
|
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA
|
0.24%
1/421
|
|
Reproductive system and breast disorders
MENOMETRORRHAGIA
|
0.24%
1/421
|
|
Reproductive system and breast disorders
POLYMENORRHOEA
|
0.24%
1/421
|
|
Reproductive system and breast disorders
PROSTATITIS
|
0.24%
1/421
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME
|
0.24%
1/421
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.24%
1/421
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.24%
1/421
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.24%
1/421
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA
|
0.24%
1/421
|
|
Respiratory, thoracic and mediastinal disorders
VOCAL CORD CYST
|
0.24%
1/421
|
|
Skin and subcutaneous tissue disorders
PSORIASIS
|
0.24%
1/421
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.48%
2/421
|
|
Vascular disorders
AORTIC STENOSIS
|
0.24%
1/421
|
|
Vascular disorders
PERIPHERAL ISCHAEMIA
|
0.24%
1/421
|
Other adverse events
| Measure |
Nilotinib
n=421 participants at risk
Nilotinib 300 mg BID
|
|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
10.2%
43/421
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
10.7%
45/421
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
18.5%
78/421
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
6.9%
29/421
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
7.1%
30/421
|
|
Gastrointestinal disorders
CONSTIPATION
|
12.1%
51/421
|
|
Gastrointestinal disorders
DIARRHOEA
|
9.7%
41/421
|
|
Gastrointestinal disorders
DYSPEPSIA
|
7.1%
30/421
|
|
Gastrointestinal disorders
NAUSEA
|
14.3%
60/421
|
|
Gastrointestinal disorders
VOMITING
|
6.9%
29/421
|
|
General disorders
FATIGUE
|
11.4%
48/421
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
7.6%
32/421
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
10.5%
44/421
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
12.1%
51/421
|
|
Investigations
AMYLASE INCREASED
|
5.9%
25/421
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
9.3%
39/421
|
|
Investigations
BLOOD CHOLESTEROL INCREASED
|
5.9%
25/421
|
|
Investigations
LIPASE INCREASED
|
15.7%
66/421
|
|
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA
|
9.0%
38/421
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
6.7%
28/421
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
5.7%
24/421
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
6.7%
28/421
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
5.9%
25/421
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
7.6%
32/421
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
5.9%
25/421
|
|
Nervous system disorders
DIZZINESS
|
6.7%
28/421
|
|
Nervous system disorders
HEADACHE
|
18.3%
77/421
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
5.7%
24/421
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
11.9%
50/421
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
6.7%
28/421
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
11.9%
50/421
|
|
Skin and subcutaneous tissue disorders
RASH
|
18.1%
76/421
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Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER