Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00760877
• Collaborator: (none)
• Enrollment: 207
• Locations: 30
• Arms: 2
• Duration (Months): 73
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary goal of this study was to determine the rate of confirmed best cumulative complete molecular response (CMR) within the first year of study therapy with imatinib or nilotinib. The study also explored the impact and significance of the achieved CMR on patient outcomes (progression free survival (PFS), event free survival (EFS) and overall survival (OS), characterized the kinetics of CMR achieved in both treatment arms and after the cross-over.

Condition or Disease	Intervention/Treatment	Phase
CHRONIC MYELOGENOUS LEUKEMIA	Drug: Nilotinib; Drug: Imatinib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Randomized Study of Nilotinib vs. Standard Imatinib (400/600 mg QD) Comparing the Kinetics of Complete Molecular Response for CML-CP Patients With Evidence of Persistent Leukemia by RQ-PCR.
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nilotinib Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Drug: Nilotinib; Supplied in 200 mg capsules
Active Comparator: Imatinib Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.	Drug: Imatinib; Supplied in 100 mg and 400 mg capsules; Other Names: Glivec/Gleevec

Outcome Measures

Primary Outcome Measures

1. Rate of Confirmed Best Cumulative Complete Molecular Response (CMR) [12 months]

   The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the first 12 months of treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by real-time quantitative polymerase chain reaction (RQ-PCR) where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.

Secondary Outcome Measures

1. Rate of Confirmed Best Cumulative CMR [24 months, 36 month, 48 months]

   The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the 24, 36 and 48 months post treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.

2. Number of Cross-over Participants With CMR [24 months, 36 months, 48 months]

   The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.

3. Progression Free Survival (PFS) [48 months]

   PFS was defined as the time from the date of randomization to the date of the earliest documented progression-defining event as follows: transformation to blast crisis or accelerated phase disease, or death from any cause.

4. Event-free Survival [48 months]

   Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.

5. Overall Survival [48 months]

   Overall survival was defined as the time from the date of randomization to the date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Diagnosis of chronic myeloid leukemia associated with BCR-ABL quantifiable by RQ-PCR Documented CCyR by bone marrow or BCR-ABL<1% IS in the past 12 months Persistent disease demonstrated by two PCR positive tests 3 months apart both during the past 6 months.

Treatment with imatinib for at least 2 years with 400 mg or 600 mg and a stable dose No other current or planned anti-leukemia therapies

Exclusion Criteria:

Patient has evidence of rising PCR (a confirmed >1 log increase in previous 6 months) Patient has received another investigational agent within last 6 months or tyrosine kinase inhibitors (TKIs) other than imatinib Prior allogeneic stem cell transplantation

Impaired cardiac function including any one of the following:

Inability to monitor the QT interval on electrocardiogram (ECG) Long QT syndrome or a known family history of long QT syndrome. Clinically significant resting brachycardia (<50 beats per minute) QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc Myocardial infarction within 12 months prior to starting study Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) History of or presence of clinically significant ventricular or atrial tachyarrhythmias Administration of cytokine therapy (e.g. G-CSF, GM-CSF or SCF) within 4 weeks prior to study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1221ADH
2	Novartis Investigative Site	St. Leonards	New South Wales	Australia	2065
3	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
4	Novartis Investigative Site	Herston	Queensland	Australia	4029
5	Novartis Investigative Site	South Brisbane	Queensland	Australia	4101
6	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
7	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
8	Novartis Investigative Site	Parkville	Victoria	Australia	3050
9	Novartis Investigative Site	Prahran	Victoria	Australia	3181
10	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
11	Novartis Investigative Site	Belo Horizonte	MG	Brazil	30130-100
12	Novartis Investigative Site	Curitiba	PR	Brazil	80060-900
13	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	21941-913
14	Novartis Investigative Site	Campinas	SP	Brazil	13083-970
15	Novartis Investigative Site	Sao Paulo	SP	Brazil	05403-000
16	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 1M9
17	Novartis Investigative Site	Hamilton	Ontario	Canada	L8H 4J9
18	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
19	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
20	Novartis Investigative Site	Québec	Quebec	Canada	G1J 1Z4
21	Novartis Investigative Site	Bordeaux		France	33076
22	Novartis Investigative Site	Creteil		France	94010
23	Novartis Investigative Site	Lyon cedex 04		France	69317
24	Novartis Investigative Site	Paris		France	75010
25	Novartis Investigative Site	Vandoeuvre les Nancy		France	54511
26	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
27	Novartis Investigative Site	Barcelona	Cataluña	Spain	08036
28	Novartis Investigative Site	Pamplona	Navarra	Spain	31008
29	Novartis Investigative Site	Madrid		Spain	28006
30	Novartis Investigative Site	Madrid		Spain	28007

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: NCT00760877
• Other Study ID Numbers: CAMN107A2405; 2009-012616-40
• First Posted: Sep 26, 2008
• Last Update Posted: Nov 8, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Novartis Pharmaceuticals: MYELOGENOUS; LEUKEMIA; Chronic Phase; CML
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized 1:1. Participants in the imatinib arm were permitted to cross-over to nilotinib after 2 years on study if complete molecular response (CMR) was not achieved, or at any time during the study if participants experienced treatment failure, had confirmed loss of major molecular response (MMR) or had confirmed loss of CMR.

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Period Title: Overall Study
STARTED	104	103
Cross-over to Nilotinib	0	46
Safety Set	101	103
COMPLETED	59	77
NOT COMPLETED	45	26

Baseline Characteristics

Arm/Group Title	Nilotinib	Imatinib	Total
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.	Total of all reporting groups
Overall Participants	104	103	207
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.3 (13.26)	49.9 (13.07)	49.1 (13.16)
Sex: Female, Male (Count of Participants)
Female	33 31.7%	38 36.9%	71 34.3%
Male	71 68.3%	65 63.1%	136 65.7%

Outcome Measures

1. Primary Outcome

Title	Rate of Confirmed Best Cumulative Complete Molecular Response (CMR)
Description	The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the first 12 months of treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by real-time quantitative polymerase chain reaction (RQ-PCR) where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set, which included all randomized participants, was analyzed.

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Measure Participants	104	103
Responders	13 12.5%	6 5.8%
Non-responders	91 87.5%	97 94.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nilotinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1083
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.096
	Confidence Interval	(2-Sided) 95%; 0.766 to 5.738
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Rate of Confirmed Best Cumulative CMR
Description	The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the 24, 36 and 48 months post treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.
Time Frame	24 months, 36 month, 48 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set, which included all randomized participants, was analyzed.

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Measure Participants	104	103
24 months, Responders	24 23.1%	11 10.7%
24 months, Non-responders	80 76.9%	92 89.3%
36 months, Responders	29 27.9%	21 20.4%
36 months, Non-responders	75 72.1%	82 79.6%
48 months, Responders	32 30.8%	21 20.4%
48 months, Non-responders	72 69.2%	82 79.6%

3. Secondary Outcome

Title	Number of Cross-over Participants With CMR
Description	The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.
Time Frame	24 months, 36 months, 48 months

Outcome Measure Data

Analysis Population Description

Participants from the Imatinib treatment group who crossed over to the Nilotinib treatment group were analyzed.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.
Measure Participants	46
24 months	3 2.9%
36 months	6 5.8%
48 months	9 8.7%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time from the date of randomization to the date of the earliest documented progression-defining event as follows: transformation to blast crisis or accelerated phase disease, or death from any cause.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

24 months, Non-responders

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Measure Participants	104	103
Median (95% Confidence Interval) [months]	NA	NA

5. Secondary Outcome

Title	Event-free Survival
Description	Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set, which included all randomized participants, was analyzed.

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Measure Participants	104	103
Median (95% Confidence Interval) [Months]	NA	NA

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival was defined as the time from the date of randomization to the date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set, which included all randomized participants, was analyzed.

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.	Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Measure Participants	104	103
Median (95% Confidence Interval) [Months]	NA	NA

Adverse Events

Arm/Group Title	Nilotinib		Imatinib		Imatinib Subset That Crossed Over to Nilotinib
Arm/Group Description	Nilotinib		Imatinib		Imatinib subset that crossed over to nilotinib
All Cause Mortality
	Nilotinib		Imatinib		Imatinib Subset That Crossed Over to Nilotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nilotinib		Imatinib		Imatinib Subset That Crossed Over to Nilotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/101 (20.8%)		16/103 (15.5%)		8/46 (17.4%)
Cardiac disorders
ACUTE CORONARY SYNDROME	1/101 (1%)		0/103 (0%)		1/46 (2.2%)
ACUTE MYOCARDIAL INFARCTION	1/101 (1%)		0/103 (0%)		0/46 (0%)
ATRIAL FIBRILLATION	1/101 (1%)		2/103 (1.9%)		0/46 (0%)
ATRIAL FLUTTER	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
CARDIOPULMONARY FAILURE	1/101 (1%)		0/103 (0%)		0/46 (0%)
CORONARY ARTERY DISEASE	1/101 (1%)		0/103 (0%)		0/46 (0%)
LEFT VENTRICULAR DYSFUNCTION	0/101 (0%)		1/103 (1%)		0/46 (0%)
MYOCARDIAL INFARCTION	0/101 (0%)		1/103 (1%)		0/46 (0%)
PERICARDITIS	0/101 (0%)		1/103 (1%)		0/46 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/101 (1%)		0/103 (0%)		0/46 (0%)
ANAL FISSURE	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
CROHN'S DISEASE	1/101 (1%)		0/103 (0%)		0/46 (0%)
INGUINAL HERNIA	0/101 (0%)		1/103 (1%)		0/46 (0%)
General disorders
INFLUENZA LIKE ILLNESS	1/101 (1%)		0/103 (0%)		0/46 (0%)
PYREXIA	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
Hepatobiliary disorders
CHOLECYSTITIS	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
CHOLELITHIASIS	1/101 (1%)		1/103 (1%)		0/46 (0%)
Infections and infestations
CELLULITIS	0/101 (0%)		2/103 (1.9%)		0/46 (0%)
ERYSIPELAS	1/101 (1%)		0/103 (0%)		0/46 (0%)
INFECTED SKIN ULCER	1/101 (1%)		0/103 (0%)		0/46 (0%)
LOWER RESPIRATORY TRACT INFECTION	1/101 (1%)		0/103 (0%)		0/46 (0%)
LUNG INFECTION	0/101 (0%)		1/103 (1%)		0/46 (0%)
OSTEOMYELITIS	1/101 (1%)		0/103 (0%)		0/46 (0%)
PNEUMONIA	0/101 (0%)		1/103 (1%)		1/46 (2.2%)
Injury, poisoning and procedural complications
ANKLE FRACTURE	1/101 (1%)		0/103 (0%)		0/46 (0%)
BACK INJURY	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
DRUG ADMINISTRATION ERROR	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
LIGAMENT RUPTURE	1/101 (1%)		0/103 (0%)		0/46 (0%)
MUSCLE INJURY	1/101 (1%)		0/103 (0%)		0/46 (0%)
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
SPINAL COLUMN STENOSIS	1/101 (1%)		0/103 (0%)		0/46 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACUTE MYELOID LEUKAEMIA	0/101 (0%)		1/103 (1%)		0/46 (0%)
MALIGNANT MELANOMA	1/101 (1%)		0/103 (0%)		0/46 (0%)
METASTASES TO PERITONEUM	0/101 (0%)		1/103 (1%)		0/46 (0%)
NON-SMALL CELL LUNG CANCER METASTATIC	0/101 (0%)		1/103 (1%)		0/46 (0%)
PROSTATE CANCER	0/101 (0%)		2/103 (1.9%)		0/46 (0%)
RENAL CELL CARCINOMA	1/101 (1%)		0/103 (0%)		0/46 (0%)
Nervous system disorders
CEREBRAL ARTERY OCCLUSION	1/101 (1%)		0/103 (0%)		0/46 (0%)
CEREBRAL ISCHAEMIA	1/101 (1%)		0/103 (0%)		0/46 (0%)
CEREBROVASCULAR ACCIDENT	1/101 (1%)		0/103 (0%)		1/46 (2.2%)
EMBOLIC STROKE	1/101 (1%)		0/103 (0%)		0/46 (0%)
Renal and urinary disorders
BLADDER DILATATION	1/101 (1%)		0/103 (0%)		0/46 (0%)
NEPHROLITHIASIS	0/101 (0%)		2/103 (1.9%)		0/46 (0%)
URINARY RETENTION	0/101 (0%)		1/103 (1%)		0/46 (0%)
Respiratory, thoracic and mediastinal disorders
LUNG DISORDER	1/101 (1%)		0/103 (0%)		0/46 (0%)
PLEURAL EFFUSION	0/101 (0%)		2/103 (1.9%)		0/46 (0%)
Vascular disorders
DEEP VEIN THROMBOSIS	0/101 (0%)		1/103 (1%)		0/46 (0%)
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	1/101 (1%)		0/103 (0%)		0/46 (0%)
PERIPHERAL VASCULAR DISORDER	0/101 (0%)		0/103 (0%)		1/46 (2.2%)
VASCULITIS	1/101 (1%)		0/103 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	Nilotinib		Imatinib		Imatinib Subset That Crossed Over to Nilotinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/101 (98%)		79/103 (76.7%)		39/46 (84.8%)
Blood and lymphatic system disorders
ANAEMIA	6/101 (5.9%)		12/103 (11.7%)		5/46 (10.9%)
Eye disorders
CONJUNCTIVAL HAEMORRHAGE	1/101 (1%)		6/103 (5.8%)		0/46 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	12/101 (11.9%)		8/103 (7.8%)		5/46 (10.9%)
ABDOMINAL PAIN UPPER	13/101 (12.9%)		7/103 (6.8%)		5/46 (10.9%)
CONSTIPATION	15/101 (14.9%)		0/103 (0%)		3/46 (6.5%)
DIARRHOEA	14/101 (13.9%)		19/103 (18.4%)		4/46 (8.7%)
NAUSEA	22/101 (21.8%)		16/103 (15.5%)		4/46 (8.7%)
VOMITING	11/101 (10.9%)		6/103 (5.8%)		0/46 (0%)
General disorders
ASTHENIA	9/101 (8.9%)		4/103 (3.9%)		5/46 (10.9%)
FATIGUE	16/101 (15.8%)		8/103 (7.8%)		6/46 (13%)
INFLUENZA LIKE ILLNESS	7/101 (6.9%)		3/103 (2.9%)		2/46 (4.3%)
OEDEMA PERIPHERAL	6/101 (5.9%)		7/103 (6.8%)		1/46 (2.2%)
PAIN	7/101 (6.9%)		3/103 (2.9%)		1/46 (2.2%)
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	10/101 (9.9%)		0/103 (0%)		6/46 (13%)
Infections and infestations
FOLLICULITIS	8/101 (7.9%)		0/103 (0%)		2/46 (4.3%)
INFLUENZA	9/101 (8.9%)		9/103 (8.7%)		2/46 (4.3%)
NASOPHARYNGITIS	9/101 (8.9%)		5/103 (4.9%)		2/46 (4.3%)
UPPER RESPIRATORY TRACT INFECTION	20/101 (19.8%)		14/103 (13.6%)		7/46 (15.2%)
URINARY TRACT INFECTION	8/101 (7.9%)		1/103 (1%)		2/46 (4.3%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	19/101 (18.8%)		5/103 (4.9%)		8/46 (17.4%)
AMYLASE INCREASED	9/101 (8.9%)		7/103 (6.8%)		2/46 (4.3%)
ASPARTATE AMINOTRANSFERASE INCREASED	14/101 (13.9%)		10/103 (9.7%)		6/46 (13%)
BILIRUBIN CONJUGATED INCREASED	4/101 (4%)		0/103 (0%)		4/46 (8.7%)
BLOOD BILIRUBIN INCREASED	10/101 (9.9%)		1/103 (1%)		2/46 (4.3%)
BLOOD CHOLESTEROL INCREASED	8/101 (7.9%)		2/103 (1.9%)		0/46 (0%)
BLOOD CREATINE PHOSPHOKINASE INCREASED	1/101 (1%)		9/103 (8.7%)		2/46 (4.3%)
BLOOD CREATININE INCREASED	6/101 (5.9%)		10/103 (9.7%)		2/46 (4.3%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED	8/101 (7.9%)		2/103 (1.9%)		2/46 (4.3%)
GLOBULINS DECREASED	4/101 (4%)		8/103 (7.8%)		0/46 (0%)
HIGH DENSITY LIPOPROTEIN DECREASED	2/101 (2%)		6/103 (5.8%)		3/46 (6.5%)
LIPASE INCREASED	19/101 (18.8%)		13/103 (12.6%)		7/46 (15.2%)
LOW DENSITY LIPOPROTEIN INCREASED	2/101 (2%)		3/103 (2.9%)		4/46 (8.7%)
WEIGHT DECREASED	10/101 (9.9%)		5/103 (4.9%)		2/46 (4.3%)
Metabolism and nutrition disorders
DECREASED APPETITE	8/101 (7.9%)		6/103 (5.8%)		1/46 (2.2%)
HYPERCHOLESTEROLAEMIA	11/101 (10.9%)		6/103 (5.8%)		7/46 (15.2%)
HYPERGLYCAEMIA	4/101 (4%)		6/103 (5.8%)		6/46 (13%)
HYPERTRIGLYCERIDAEMIA	3/101 (3%)		7/103 (6.8%)		2/46 (4.3%)
HYPOPHOSPHATAEMIA	9/101 (8.9%)		13/103 (12.6%)		7/46 (15.2%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	16/101 (15.8%)		10/103 (9.7%)		6/46 (13%)
BACK PAIN	12/101 (11.9%)		9/103 (8.7%)		7/46 (15.2%)
MUSCLE SPASMS	15/101 (14.9%)		18/103 (17.5%)		1/46 (2.2%)
MUSCULOSKELETAL PAIN	10/101 (9.9%)		8/103 (7.8%)		2/46 (4.3%)
MYALGIA	14/101 (13.9%)		2/103 (1.9%)		6/46 (13%)
PAIN IN EXTREMITY	14/101 (13.9%)		4/103 (3.9%)		8/46 (17.4%)
Nervous system disorders
DIZZINESS	5/101 (5%)		6/103 (5.8%)		3/46 (6.5%)
HEADACHE	43/101 (42.6%)		13/103 (12.6%)		8/46 (17.4%)
Psychiatric disorders
DEPRESSION	6/101 (5.9%)		4/103 (3.9%)		2/46 (4.3%)
INSOMNIA	12/101 (11.9%)		5/103 (4.9%)		2/46 (4.3%)
Respiratory, thoracic and mediastinal disorders
COUGH	11/101 (10.9%)		9/103 (8.7%)		4/46 (8.7%)
DYSPNOEA	3/101 (3%)		1/103 (1%)		3/46 (6.5%)
OROPHARYNGEAL PAIN	6/101 (5.9%)		6/103 (5.8%)		0/46 (0%)
Skin and subcutaneous tissue disorders
ALOPECIA	11/101 (10.9%)		0/103 (0%)		4/46 (8.7%)
DRY SKIN	20/101 (19.8%)		0/103 (0%)		3/46 (6.5%)
PRURITUS	30/101 (29.7%)		0/103 (0%)		2/46 (4.3%)
RASH	30/101 (29.7%)		4/103 (3.9%)		9/46 (19.6%)
RASH FOLLICULAR	4/101 (4%)		0/103 (0%)		3/46 (6.5%)
Vascular disorders
HYPERTENSION	10/101 (9.9%)		6/103 (5.8%)		1/46 (2.2%)

Limitations/Caveats

[Not Specified]

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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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.