ENESTxtnd: Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01254188
• Collaborator: (none)
• Enrollment: 421
• Locations: 100
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: Nilotinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 421 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Nilotinib 300 mg BID

Drug: Nilotinib; This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid.; Other Names: AMN107

Outcome Measures

Primary Outcome Measures

1. The Percentage of Patients Achieving MMR by 12 Months [12 months]

   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

Secondary Outcome Measures

1. Time to Molecular Response at 24 Months [24 months]

   Estimated median time to first MMR by Kaplan-Meier method

2. Duration of Major Molecular Response [3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected]

   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

3. Complete Cytogenetic Response [6 months]

   Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.

4. 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. [6,12,18 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

5. Overall Survival [3, 6, 9, 12, 15, 18, 21, 24 Months]

   OS 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.

6. Kaplan-Meier Estimates of Progression-free Survival [3,6,9,12,15,18,21,and 24 months]

   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.

7. Kaplan-Meier Estimates of Failure-free Survival [3,6,9,12,15,18,21,and 24 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

-Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry

Exclusion Criteria:

• Treatment with tyrosine kinase inhibitor or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with exception of hydroxyurea and/or anagrelide

• Uncontrolled congestive heart failure or hypertension

• Myocardial infarction or unstable angina pectoris within past 12 months

• Known T315I mutations

• QTcF >450 msec

• Significant arrhythmias

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Alger	Bouzareah	Algeria	16000
2	Novartis Investigative Site	Oran		Algeria	31000
3	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1221ADC
4	Novartis Investigative Site	Paraná	Entre Rios	Argentina	E3100BBJ
5	Novartis Investigative Site	Buenos Aires		Argentina	C1114AAN
6	Novartis Investigative Site	Canberra	Australian Capital Territory	Australia	2605
7	Novartis Investigative Site	Concord NSW	New South Wales	Australia	2139
8	Novartis Investigative Site	Gosford	New South Wales	Australia	2250
9	Novartis Investigative Site	Kingswood	New South Wales	Australia	2747
10	Novartis Investigative Site	Kogarah	New South Wales	Australia	2217
11	Novartis Investigative Site	Liverpool	New South Wales	Australia	2170
12	Novartis Investigative Site	St. Leonards	New South Wales	Australia	2065
13	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
14	Novartis Investigative Site	Douglas	Queensland	Australia	4810
15	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
16	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
17	Novartis Investigative Site	Bedford Park	South Australia	Australia	5042
18	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
19	Novartis Investigative Site	Box Hill	Victoria	Australia	3128
20	Novartis Investigative Site	Clayton	Victoria	Australia	3168
21	Novartis Investigative Site	Fitzroy	Victoria	Australia	3065
22	Novartis Investigative Site	Heidelberg	Victoria	Australia	3084
23	Novartis Investigative Site	Parkville	Victoria	Australia	3050
24	Novartis Investigative Site	Wodonga	Victoria	Australia	3690
25	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
26	Novartis Investigative Site	Perth	Western Australia	Australia	6000
27	Novartis Investigative Site	Salvador	BA	Brazil	41253-190
28	Novartis Investigative Site	Goiania	GO	Brazil	74605-020
29	Novartis Investigative Site	Curitiba	PR	Brazil	81520-060
30	Novartis Investigative Site	Porto Alegre	RS	Brazil	90430-091
31	Novartis Investigative Site	Edmonton	Alberta	Canada	T6G 1Z2
32	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 1M9
33	Novartis Investigative Site	Vancouver	British Columbia	Canada	V6Z1Y6
34	Novartis Investigative Site	Moncton	New Brunswick	Canada	E1C 6Z8
35	Novartis Investigative Site	Saint John	New Brunswick	Canada	E2L 4L2
36	Novartis Investigative Site	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
37	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 1V7
38	Novartis Investigative Site	Barrie	Ontario	Canada	L4M 6M2
39	Novartis Investigative Site	Brampton	Ontario	Canada	L6R 3J7
40	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
41	Novartis Investigative Site	London	Ontario	Canada	N6A 4G5
42	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
43	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
44	Novartis Investigative Site	Weston	Ontario	Canada	M9N 1N8
45	Novartis Investigative Site	Windsor	Ontario	Canada	N8W 2X3
46	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
47	Novartis Investigative Site	Québec	Quebec	Canada	G1J 1Z4
48	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7N 4H4
49	Novartis Investigative Site	Alexandria		Egypt	21131
50	Novartis Investigative Site	Cairo		Egypt	11566
51	Novartis Investigative Site	Cairo		Egypt
52	Novartis Investigative Site	Mansoura		Egypt	35516
53	Novartis Investigative Site	Tamil Nadu	Chennai	India	600035
54	Novartis Investigative Site	Pune	Maharashtra	India	411004
55	Novartis Investigative Site	Vellore	Tamil Nadu	India	632004
56	Novartis Investigative Site	Jerusalem		Israel	9112001
57	Novartis Investigative Site	Petach Tikva		Israel	49100
58	Novartis Investigative Site	Ramat Gan		Israel	5266202
59	Novartis Investigative Site	Beirut		Lebanon	166830
60	Novartis Investigative Site	Saida		Lebanon	652
61	Novartis Investigative Site	Pulau Pinang		Malaysia	10990
62	Novartis Investigative Site	Selangor		Malaysia	68000
63	Novartis Investigative Site	Hermosillo	Sonora	Mexico	83000
64	Novartis Investigative Site	San Luis Potosi		Mexico	78416
65	Novartis Investigative Site	Muscat		Oman	123
66	Novartis Investigative Site	Arkhangelsk	Russia	Russian Federation	163045
67	Novartis Investigative Site	Novosibirsk	Russia	Russian Federation	630051
68	Novartis Investigative Site	Perm	Russia	Russian Federation	614077
69	Novartis Investigative Site	Ryazan	Russia	Russian Federation	390039
70	Novartis Investigative Site	St Petersburg	Russia	Russian Federation	197341
71	Novartis Investigative Site	Tumen	Russia	Russian Federation	625023
72	Novartis Investigative Site	Ekaterinburg		Russian Federation	620137
73	Novartis Investigative Site	Irkutsk		Russian Federation	664079
74	Novartis Investigative Site	Moscow		Russian Federation	125167
75	Novartis Investigative Site	Moscow		Russian Federation	125284
76	Novartis Investigative Site	Nizhnii Novgorod		Russian Federation	603126
77	Novartis Investigative Site	Rostov-on-Don		Russian Federation	344022
78	Novartis Investigative Site	Rostov-on-Don		Russian Federation	344090
79	Novartis Investigative Site	St Petersburg		Russian Federation	191024
80	Novartis Investigative Site	St-Petersburg		Russian Federation	197022
81	Novartis Investigative Site	Tula		Russian Federation	300053
82	Novartis Investigative Site	Dammam		Saudi Arabia	15215
83	Novartis Investigative Site	Jeddah		Saudi Arabia	21423
84	Novartis Investigative Site	Jeddah		Saudi Arabia	21499
85	Novartis Investigative Site	Riyadh		Saudi Arabia	11211
86	Novartis Investigative Site	Riyadh		Saudi Arabia	11426
87	Novartis Investigative Site	Soweto	Gauteng	South Africa	2013
88	Novartis Investigative Site	Bloemfontein		South Africa	9301
89	Novartis Investigative Site	Observatory		South Africa	7925
90	Novartis Investigative Site	Parktown		South Africa	2193
91	Novartis Investigative Site	Pretoria		South Africa	0002
92	Novartis Investigative Site	Taipei	Taiwan, ROC	Taiwan	112
93	Novartis Investigative Site	Lin-Kou		Taiwan	33305
94	Novartis Investigative Site	Niaosong Township		Taiwan	83301
95	Novartis Investigative Site	Taichung		Taiwan	40447
96	Novartis Investigative Site	Chiang Mai		Thailand	50200
97	Novartis Investigative Site	Muang		Thailand	40002
98	Novartis Investigative Site	Sousse	Tunisie	Tunisia	4000
99	Novartis Investigative Site	Tunis		Tunisia	1008
100	Novartis Investigative Site	Dubai		United Arab Emirates

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01254188
• Other Study ID Numbers: CAMN107E2401; NCT01580059
• First Posted: Dec 6, 2010
• Last Update Posted: Mar 3, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Chronic myeloid leukemia,; CML,; nilotinib,; myelogenous,; Philadelphia chromosome
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

Participant Flow

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Period Title: Overall Study
STARTED	421
COMPLETED	328
NOT COMPLETED	93

Baseline Characteristics

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Overall Participants	421
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	368 87.4%
>=65 years	53 12.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.13 (14.892)
Sex: Female, Male (Count of Participants)
Female	195 46.3%
Male	226 53.7%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Patients Achieving MMR by 12 Months
Description	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
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
Number (95% Confidence Interval) [percentage of participants]	70.8 16.8%

2. Secondary Outcome

Title	Time to Molecular Response at 24 Months
Description	Estimated median time to first MMR by Kaplan-Meier method
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
Median (95% Confidence Interval) [Months]	6.0

3. Secondary Outcome

Title	Duration of Major Molecular Response
Description	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
Time Frame	3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected

Outcome Measure Data

Analysis Population Description

Full Analysis set, Number of events / censored 29/312.

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
K-M Estimate for 3 Month Duration	100 23.8%
K-M Estimate for 6 Month Duration	97.1 23.1%
K-M Estimate for 9 Month Duration	92.8 22%
K-M Estimate for 12 Month Duration	92.1 21.9%
K-M Estimate for 15 Month Duration	91.7 21.8%
18 months	90.8 21.6%
K-M Estimate for 21 Month Duration	89.7 21.3%
K-M Estimate for 24 Month Duration	85.2 20.2%

4. Secondary Outcome

Title	Complete Cytogenetic Response
Description	Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
Number (95% Confidence Interval) [percentage of participants]	58.7 13.9%

5. Secondary Outcome

Title	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.
Description	* 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
Time Frame	6,12,18 and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
6 mos after the first CCyR was achieved	100 23.8%
12 mos after the first CCyR was achieved	99.6 23.7%
18 mos after the first CCyR was achieved	98.7 23.4%
24 mos after the first CCyR was achieved	98.7 23.4%

6. Secondary Outcome

Title	Overall Survival
Description	OS 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.
Time Frame	3, 6, 9, 12, 15, 18, 21, 24 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
3 months K-M Estimate	99.8
6 months K-M Estimate	99.5
9 months K-M Estimate	99.5
12 months K-M Estimate	99.0
15 months K-M Estimate	98.2
18 months K-M Estimate	97.6
21 months K-M Estimate	97.6
24 months K-M Estimate	97.6

7. Secondary Outcome

Title	Kaplan-Meier Estimates of Progression-free Survival
Description	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.
Time Frame	3,6,9,12,15,18,21,and 24 months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
3 mos	99.7
6 mos	99.5
9 mos	98.9
12 mos	98.6
15 mos	98.0
18 mos	97.6
21 mos	97.6
24 mos	97.0

8. Secondary Outcome

Title	Kaplan-Meier Estimates of Failure-free Survival
Description	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.
Time Frame	3,6,9,12,15,18,21,and 24 months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
Measure Participants	421
3 mos	97.4
6 mos	95.9
9 mos	94.6
12 mos	93.6
15 mos	92.0
18 mos	91.0
21 mos	89.7
24 mos	88.8

Adverse Events

Arm/Group Title	Nilotinib
Arm/Group Description	Nilotinib 300 mg BID
All Cause Mortality
	Nilotinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nilotinib
	Affected / at Risk (%)	# Events
Total	97/421 (23%)
Blood and lymphatic system disorders
AGRANULOCYTOSIS	1/421 (0.2%)
ANAEMIA	4/421 (1%)
FEBRILE NEUTROPENIA	4/421 (1%)
LEUKOCYTOSIS	1/421 (0.2%)
LEUKOPENIA	2/421 (0.5%)
NEUTROPENIA	3/421 (0.7%)
PANCYTOPENIA	2/421 (0.5%)
THROMBOCYTOPENIA	12/421 (2.9%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	2/421 (0.5%)
ANGINA PECTORIS	2/421 (0.5%)
ANGINA UNSTABLE	3/421 (0.7%)
ARRHYTHMIA	1/421 (0.2%)
ATRIAL FIBRILLATION	4/421 (1%)
CARDIAC ARREST	1/421 (0.2%)
CARDIAC FAILURE	1/421 (0.2%)
CARDIAC TAMPONADE	1/421 (0.2%)
CARDIO-RESPIRATORY ARREST	1/421 (0.2%)
CORONARY ARTERY DISEASE	2/421 (0.5%)
MYOCARDIAL INFARCTION	2/421 (0.5%)
MYOCARDIAL ISCHAEMIA	2/421 (0.5%)
SINUS BRADYCARDIA	1/421 (0.2%)
Endocrine disorders
HYPERTHYROIDISM	1/421 (0.2%)
Eye disorders
CATARACT	2/421 (0.5%)
RETINAL VEIN OCCLUSION	1/421 (0.2%)
VITREOUS HAEMORRHAGE	1/421 (0.2%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/421 (0.2%)
ABDOMINAL PAIN UPPER	1/421 (0.2%)
CONSTIPATION	2/421 (0.5%)
DUODENAL ULCER	1/421 (0.2%)
GASTROINTESTINAL PAIN	1/421 (0.2%)
HYPERCHLORHYDRIA	1/421 (0.2%)
INGUINAL HERNIA	1/421 (0.2%)
INTESTINAL INFARCTION	1/421 (0.2%)
NAUSEA	1/421 (0.2%)
PANCREATITIS	7/421 (1.7%)
PANCREATITIS ACUTE	1/421 (0.2%)
RECTAL HAEMORRHAGE	1/421 (0.2%)
VOMITING	1/421 (0.2%)
General disorders
ASTHENIA	1/421 (0.2%)
GENERALISED OEDEMA	1/421 (0.2%)
PAIN	1/421 (0.2%)
PYREXIA	3/421 (0.7%)
SUDDEN DEATH	1/421 (0.2%)
Hepatobiliary disorders
CHOLECYSTITIS ACUTE	2/421 (0.5%)
CHOLELITHIASIS	1/421 (0.2%)
DRUG-INDUCED LIVER INJURY	1/421 (0.2%)
Infections and infestations
ANAL ABSCESS	1/421 (0.2%)
APPENDICITIS	1/421 (0.2%)
CELLULITIS	1/421 (0.2%)
DIARRHOEA INFECTIOUS	1/421 (0.2%)
GASTROENTERITIS	1/421 (0.2%)
LOWER RESPIRATORY TRACT INFECTION	1/421 (0.2%)
PHARYNGITIS	1/421 (0.2%)
PNEUMONIA	4/421 (1%)
PYELONEPHRITIS CHRONIC	1/421 (0.2%)
TRACHEOBRONCHITIS	1/421 (0.2%)
Injury, poisoning and procedural complications
LACERATION	2/421 (0.5%)
ROAD TRAFFIC ACCIDENT	1/421 (0.2%)
Investigations
AMYLASE INCREASED	2/421 (0.5%)
BLOOD BILIRUBIN INCREASED	2/421 (0.5%)
LIPASE INCREASED	1/421 (0.2%)
LIVER FUNCTION TEST ABNORMAL	1/421 (0.2%)
Metabolism and nutrition disorders
DEHYDRATION	2/421 (0.5%)
HYPERGLYCAEMIA	1/421 (0.2%)
HYPERLIPASAEMIA	1/421 (0.2%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/421 (0.2%)
BACK PAIN	1/421 (0.2%)
MUSCULOSKELETAL CHEST PAIN	1/421 (0.2%)
ROTATOR CUFF SYNDROME	1/421 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA	1/421 (0.2%)
BLAST CELL CRISIS	3/421 (0.7%)
MALIGNANT NEOPLASM PROGRESSION	1/421 (0.2%)
METASTATIC MALIGNANT MELANOMA	1/421 (0.2%)
SQUAMOUS CELL CARCINOMA	1/421 (0.2%)
Nervous system disorders
CEREBRAL HAEMATOMA	1/421 (0.2%)
CEREBROVASCULAR ACCIDENT	1/421 (0.2%)
HAEMORRHAGIC STROKE	1/421 (0.2%)
HEADACHE	1/421 (0.2%)
INTRACRANIAL PRESSURE INCREASED	1/421 (0.2%)
MYASTHENIA GRAVIS	1/421 (0.2%)
SCIATICA	1/421 (0.2%)
Renal and urinary disorders
NEPHROLITHIASIS	2/421 (0.5%)
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	1/421 (0.2%)
MENOMETRORRHAGIA	1/421 (0.2%)
POLYMENORRHOEA	1/421 (0.2%)
PROSTATITIS	1/421 (0.2%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME	1/421 (0.2%)
ASTHMA	1/421 (0.2%)
DYSPNOEA	1/421 (0.2%)
PULMONARY EMBOLISM	1/421 (0.2%)
PULMONARY OEDEMA	1/421 (0.2%)
VOCAL CORD CYST	1/421 (0.2%)
Skin and subcutaneous tissue disorders
PSORIASIS	1/421 (0.2%)
RASH	2/421 (0.5%)
Vascular disorders
AORTIC STENOSIS	1/421 (0.2%)
PERIPHERAL ISCHAEMIA	1/421 (0.2%)
Other (Not Including Serious) Adverse Events
	Nilotinib
	Affected / at Risk (%)	# Events
Total	357/421 (84.8%)
Blood and lymphatic system disorders
ANAEMIA	43/421 (10.2%)
NEUTROPENIA	45/421 (10.7%)
THROMBOCYTOPENIA	78/421 (18.5%)
Gastrointestinal disorders
ABDOMINAL PAIN	29/421 (6.9%)
ABDOMINAL PAIN UPPER	30/421 (7.1%)
CONSTIPATION	51/421 (12.1%)
DIARRHOEA	41/421 (9.7%)
DYSPEPSIA	30/421 (7.1%)
NAUSEA	60/421 (14.3%)
VOMITING	29/421 (6.9%)
General disorders
FATIGUE	48/421 (11.4%)
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	32/421 (7.6%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	44/421 (10.5%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	51/421 (12.1%)
AMYLASE INCREASED	25/421 (5.9%)
BLOOD BILIRUBIN INCREASED	39/421 (9.3%)
BLOOD CHOLESTEROL INCREASED	25/421 (5.9%)
LIPASE INCREASED	66/421 (15.7%)
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA	38/421 (9%)
HYPERGLYCAEMIA	28/421 (6.7%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	24/421 (5.7%)
BACK PAIN	28/421 (6.7%)
MUSCLE SPASMS	25/421 (5.9%)
MYALGIA	32/421 (7.6%)
PAIN IN EXTREMITY	25/421 (5.9%)
Nervous system disorders
DIZZINESS	28/421 (6.7%)
HEADACHE	77/421 (18.3%)
Respiratory, thoracic and mediastinal disorders
COUGH	24/421 (5.7%)
Skin and subcutaneous tissue disorders
ALOPECIA	50/421 (11.9%)
DRY SKIN	28/421 (6.7%)
PRURITUS	50/421 (11.9%)
RASH	76/421 (18.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.