A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00109707
• Collaborator: (none)
• Enrollment: 507
• Locations: 101
• Arms: 3
• Actual Duration (Months): 89
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions:

Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1)

Group A - Imatinib failure only (arms 2, 3 and 4)

• imatinib-resistant or intolerant CML - Chronic Phase (CP)

• imatinib-resistant or intolerant CML - Accelerated Phase (AP)

• imatinib-resistant or intolerant CML - Blast Crisis (BC)

Group B - Imatinib and other TKI failure (arms 2, 3 and 4)

• imatinib-resistant or intolerant CML - Chronic Phase (CP)

• imatinib-resistant or intolerant CML - Accelerated Phase (AP)

• imatinib-resistant or intolerant CML - Blast Crisis (BC)

Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5)

Systemic mastocytosis (Sm) (arm 6)

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive); Hypereosinophilic Syndrome; Systemic Mastocytosis	Drug: Nilotinib	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 507 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IA/II Multicenter, Dose-escalation Study of Oral AMN107 on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant/Intolerant CML in Chronic or Accelerated Phase or Blast Crisis, Relapsed/Refractory Ph+ ALL, and Other Hematologic Malignancies.
• Actual Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CML-CP With Prior Imatinib Only Imatinib-resistant / intolerant PH+ CML-CP patients	Drug: Nilotinib
Experimental: CML-AP With Prior Imatinib Onl Imatinib-resistant / intolerant PH+ CML-AP patients	Drug: Nilotinib
Experimental: CML-CP Imatinib-resistant / intolerant PH+ CML-CP patients	Drug: Nilotinib

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Major Cytogenetic Response (MCyR) [Up to End of the Treatment (Approximately 7.5 years)]

   Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

2. Number of Participants Confirmed Overall Hematological Response (Phase II) [Up to End of the Treatment (Approximately 7.5 years)]

   Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver). Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.

Secondary Outcome Measures

1. Number of Participants With Overall Major Cytogenetic Responses (Phase II) [Up to End of the Treatment (Approximately 7.5 years)]

   Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and >0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).

2. Number of Participants With Complete Hematologic Response (Phase II) [Up to End of the Treatment (Approximately 7.5 years)]

   A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; < 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

3. Participants With (MMR) Major Molecular Response (Phase II) [Up to End of the Treatment (Approximately 7.5 years)]

   MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.

4. Time to Progression (TTP) (Phase II) [Up to End of the Treatment (Approximately 7.5 years)]

   Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death. Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).

5. Overall Survival (OS) (Phase II) [Up to End of the Treatment (Approximately 7.5 years)]

   OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.

6. Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety [From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)]

   Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Main inclusion criteria include:

• Patients with CML in blast crisis, CML in accelerated phase defined as never in blast crisis phase, or CML in chronic phase defined as never been in blast crisis phase or accelerated phase who have: *developed progressive disease during therapy with at least 600 mg of imatinib per day, -OR- *patients with CML on imatinib therapy, at any dose, developing progressive disease and the presence of a genetic mutation likely to result in imatinib resistance -OR- *have developed an intolerance to imatinib

• Relapsed or refractory Ph+ ALL

• Hypereosinophilic syndrome/chronic eosinophilic leukemia.

• Systemic mastocytosis who have a clinical indication for treatment.

• Prior imatinib therapy for patients with Ph+ ALL, HES/CEL and SM is permitted but is not required

• CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible

• Written informed consent prior to any study procedures being performed

Exclusion Criteria:

• Impaired cardiac function

• Patients with severe/chronic or uncontrolled medical conditions (including but not limited to diabetes, infections, GI impairment, CNS infiltration, liver and kidney disease)

• Prior and concomitant use of certain medications (including but not limited to warfarin, chemotherapy, hematopoietic colony-stimulating growth factors, medications that can affect electrocardiogram test results, other investigational drugs )

• Women who are pregnant or breastfeeding

• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.

• Patients unwilling to comply with the protocol.

• Known diagnosis of human immunodeficiency virus (HIV) infection

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	Stanford University Medical Center	Stanford	California	United States	94305-5750
3	University of Colorado Hospital	Aurora	Colorado	United States	80045
4	H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt	Tampa	Florida	United States	33612
5	University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)	Chicago	Illinois	United States	60637
6	University of Illinois at Chicago Divisionof Hematology/Oncology	Chicago	Illinois	United States
7	Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2)	Beech Grove	Indiana	United States	46107
8	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
9	Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie	Baltimore	Maryland	United States	21231
10	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
11	University of Michigan Health System Clinical Trials Office	Ann Arbor	Michigan	United States	48109
12	Wayne State University	Detroit	Michigan	United States	48201
13	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
14	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
15	Roswell Park Cancer Institute Rosewell SC	Buffalo	New York	United States	14263
16	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10017
17	University of Rochester Medical Center	Rochester	New York	United States	14642
18	Duke University Medical Center	Durham	North Carolina	United States	27710
19	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
20	Oregon Health Sciences University	Portland	Oregon	United States	97239
21	The Jones Clinic	Germantown	Tennessee	United States	38138
22	Vanderbilt University Medical Center, Clinical Trials Center Investigational Drug Services	Nashville	Tennessee	United States	37212
23	MD Anderson Cancer Center/University of Texas	Houston	Texas	United States	77030
24	Swedish Cancer Institute	Seattle	Washington	United States	98104
25	Novartis Investigative Site	St. Leonards	New South Wales	Australia	2065
26	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
27	Novartis Investigative Site	Prahran	Victoria	Australia	3181
28	Novartis Investigative Site	Wien		Austria	A-1090
29	Novartis Investigative Site	Bruxelles		Belgium	1000
30	Novartis Investigative Site	Haine-saint-Paul		Belgium	7100
31	Novartis Investigative Site	Leuven		Belgium	3000
32	Novartis Investigative Site	Yvoir		Belgium	5530
33	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 4E3
34	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
35	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
36	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 1A1
37	Novartis Investigative Site	Vejle		Denmark	DK-7100
38	Novartis Investigative Site	HUS Helsinki		Finland	FIN-00029
39	Novartis Investigative Site	Bordeaux Cedex		France	33076
40	Novartis Investigative Site	Créteil		France	94010
41	Novartis Investigative Site	Dijon		France	21034
42	Novartis Investigative Site	Lille		France	59037
43	Novartis Investigative Site	Limoges cedex		France	87042
44	Novartis Investigative Site	Lyon		France	69437
45	Novartis Investigative Site	Marseille		France	13273
46	Novartis Investigative Site	Poitiers		France	86021
47	Novartis Investigative Site	Rennes		France	35019
48	Novartis Investigative Site	Vandoeuvre les Nancy		France	54511
49	Novartis Investigative Site	Berlin		Germany	13353
50	Novartis Investigative Site	Duesseldorf		Germany	40225
51	Novartis Investigative Site	Frankfurt/M		Germany	60590
52	Novartis Investigative Site	Hamburg		Germany	20246
53	Novartis Investigative Site	Leipzig		Germany	04103
54	Novartis Investigative Site	Mainz		Germany	55131
55	Novartis Investigative Site	Mannheim		Germany	68169
56	Novartis Investigative Site	Muenchen		Germany	81675
57	Novartis Investigative Site	Pokfulam		Hong Kong
58	Novartis Investigative Site	Bergamo	BG	Italy	24128
59	Novartis Investigative Site	Bologna	BO	Italy	40138
60	Novartis Investigative Site	Genova	GE	Italy	16132
61	Novartis Investigative Site	Monza	MB	Italy	20900
62	Novartis Investigative Site	Milano	MI	Italy	20162
63	Novartis Investigative Site	Pescara	PE	Italy	65124
64	Novartis Investigative Site	Pavia	PV	Italy	27100
65	Novartis Investigative Site	Reggio Calabria	RC	Italy	89124
66	Novartis Investigative Site	Roma	RM	Italy	00144
67	Novartis Investigative Site	Roma	RM	Italy	00161
68	Novartis Investigative Site	Roma	RM	Italy	00168
69	Novartis Investigative Site	Orbassano	TO	Italy	10043
70	Novartis Investigative Site	Napoli		Italy	80131
71	Novartis Investigative Site	Hwasun-gun	Jeollanam-do	Korea, Republic of	519-809
72	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
73	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	137-701
74	Novartis Investigative Site	Taegu		Korea, Republic of	700 - 721
75	Novartis Investigative Site	Amsterdam		Netherlands	1081 HV
76	Novartis Investigative Site	Rotterdam		Netherlands
77	Novartis Investigative Site	Grafton	Auckland	New Zealand
78	Novartis Investigative Site	Oslo		Norway	NO-0310
79	Novartis Investigative Site	Katowice		Poland	40-635
80	Novartis Investigative Site	Lodz		Poland	90-153
81	Novartis Investigative Site	Warszawa		Poland	02-097
82	Novartis Investigative Site	Warszawa		Poland	02-776
83	Novartis Investigative Site	Wroclaw		Poland	50-367
84	Novartis Investigative Site	Singapore		Singapore	169608
85	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
86	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
87	Novartis Investigative Site	Göteborg		Sweden	SE-413 45
88	Novartis Investigative Site	Linköping		Sweden	SE-581 85
89	Novartis Investigative Site	Lund		Sweden	SE-221 85
90	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
91	Novartis Investigative Site	Basel		Switzerland	4031
92	Novartis Investigative Site	Genève		Switzerland	1211
93	Novartis Investigative Site	Niaosong Township		Taiwan	83301
94	Novartis Investigative Site	Birmingham		United Kingdom	B15 2TH
95	Novartis Investigative Site	Cambridge		United Kingdom	CB2 2QQ
96	Novartis Investigative Site	Glasgow - Scotland		United Kingdom	G12 OYN
97	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
98	Novartis Investigative Site	Liverpool		United Kingdom	L7 8XP
99	Novartis Investigative Site	London		United Kingdom	SE5 9RS
100	Novartis Investigative Site	London		United Kingdom	W12 0NN
101	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE1 4LP

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticlas, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Results for CAMN107A2101 on the Novartis Clinical Trials Website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00109707
• Other Study ID Numbers: CAMN107A2101
• First Posted: May 3, 2005
• Last Update Posted: Jun 29, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Novartis Pharmaceuticals: CML in blast crisis; CML in chronic phase; CML in accelerated phase; Gleevec resistance; Gleevec intolerant; Gleevec and CML; imatinib resistance; imatinib intolerant; Hypereosinophilic Syndrome; Systemic Mastocytosis; Chronic eosinophilic syndrome; Philadelphia chromosome positive acute lymphoblastic leukemia; HES; CEL; CML; SM; Ph+ ALL refractory to standard therapy; Ph+ALL relapsed; AMN107A
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Mastocytosis; Mastocytosis, Systemic; Hypereosinophilic Syndrome; Syndrome; Philadelphia Chromosome

Study Results

Participant Flow

Recruitment Details	The study was conducted at 100 centers in 22 countries.
Pre-assignment Detail	A total of 507 participants were randomized in the core study, out of which 136 participants entered the extension study.

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP
Arm/Group Description	Adult participants PH+ CML-CP ( Chronic Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Period Title: Overall Study
STARTED	321	137	49
Entered Extension Study	106	15	15
COMPLETED	67	8	8
NOT COMPLETED	254	129	41

Baseline Characteristics

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP	Total
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Total of all reporting groups
Overall Participants	321	137	49	507
Age, Customized (Count of Participants)
<35 years	22 6.9%	8 5.8%	3 6.1%	33 6.5%
≥35 to <55 years	104 32.4%	49 35.8%	16 32.7%	169 33.3%
≥55 to <65 years	97 30.2%	39 28.5%	12 24.5%	148 29.2%
≥65 years	98 30.5%	41 29.9%	18 36.7%	157 31%
Sex: Female, Male (Count of Participants)
Female	159 49.5%	61 44.5%	25 51%	245 48.3%
Male	162 50.5%	76 55.5%	24 49%	262 51.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Major Cytogenetic Response (MCyR)
Description	Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	321	137	49
Count of Participants [Participants]	191 59.5%	44 32.1%	22 44.9%

2. Primary Outcome

Title	Number of Participants Confirmed Overall Hematological Response (Phase II)
Description	Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver). Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CML-AP With Prior Imatinib Only
Arm/Group Description	Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	137
Count of Participants [Participants]	76 23.7%

3. Secondary Outcome

Title	Number of Participants With Overall Major Cytogenetic Responses (Phase II)
Description	Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and >0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	321	137	49
Number [participants]	191 59.5%	44 32.1%	22 44.9%

4. Secondary Outcome

Title	Number of Participants With Complete Hematologic Response (Phase II)
Description	A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; < 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	321	137	35
Number [participants]	158 49.2%	76 55.5%	27 55.1%

5. Secondary Outcome

Title	Participants With (MMR) Major Molecular Response (Phase II)
Description	MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All participants who received at least one dose of study medication. Major molecular response was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8)

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	299	122
Count of Participants [Participants]	106 33%	18 13.1%

6. Secondary Outcome

Title	Time to Progression (TTP) (Phase II)
Description	Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death. Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All participants who received at least one dose of study medication. Time to progression was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8).

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	321	137
Median (Full Range) [Months]	55.6	15.9

7. Secondary Outcome

Title	Overall Survival (OS) (Phase II)
Description	OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.
Time Frame	Up to End of the Treatment (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	321	137	49
Median (95% Confidence Interval) [months]	NA	47.54	NA

8. Secondary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety
Description	Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time Frame	From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)

Outcome Measure Data

Analysis Population Description

Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.

Arm/Group Title	CML-CP With Prior Imatinib Only	CML-AP With Prior Imatinib Only	CML-CP
Arm/Group Description	Adult participants PH+ CML-CP ( Chronic Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).	Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
Measure Participants	321	137	49
Serious Adverse Events	61 19%	26 19%	5 10.2%
Adverse Events	57 17.8%	17 12.4%	7 14.3%

Adverse Events

Time Frame	From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)
Adverse Event Reporting Description	Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.
Arm/Group Title	CML-CP With Prior Imatinib Only		CML-AP With Prior Imatinib Only		CML-CP
Arm/Group Description	Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).		Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).		Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).
All Cause Mortality
	CML-CP With Prior Imatinib Only		CML-AP With Prior Imatinib Only		CML-CP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/321 (4%)		14/137 (10.2%)		0/49 (0%)
Serious Adverse Events
	CML-CP With Prior Imatinib Only		CML-AP With Prior Imatinib Only		CML-CP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/321 (45.5%)		55/137 (40.1%)		21/49 (42.9%)
Blood and lymphatic system disorders
Thrombocytopenia	11/321 (3.4%)		11/137 (8%)		3/49 (6.1%)
Neutropenia	7/321 (2.2%)		8/137 (5.8%)		0/49 (0%)
Anaemia	4/321 (1.2%)		3/137 (2.2%)		3/49 (6.1%)
Febrile neutropenia	4/321 (1.2%)		3/137 (2.2%)		2/49 (4.1%)
Leukocytosis	0/321 (0%)		4/137 (2.9%)		0/49 (0%)
Leukopenia	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Pancytopenia	0/321 (0%)		0/137 (0%)		1/49 (2%)
Cardiac disorders
Angina pectoris	12/321 (3.7%)		0/137 (0%)		0/49 (0%)
Myocardial infarction	7/321 (2.2%)		5/137 (3.6%)		0/49 (0%)
Acute myocardial infarction	6/321 (1.9%)		0/137 (0%)		0/49 (0%)
Atrial fibrillation	5/321 (1.6%)		0/137 (0%)		1/49 (2%)
Coronary artery disease	5/321 (1.6%)		0/137 (0%)		0/49 (0%)
Acute coronary syndrome	3/321 (0.9%)		0/137 (0%)		0/49 (0%)
Palpitations	3/321 (0.9%)		0/137 (0%)		0/49 (0%)
Cardiac failure congestive	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Coronary artery stenosis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Pericardial effusion	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Pericarditis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Angina pectoris	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Cardiac arrest	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Atrial flutter	0/321 (0%)		0/137 (0%)		1/49 (2%)
Myocardial infarction	0/321 (0%)		0/137 (0%)		1/49 (2%)
Ear and labyrinth disorders
Vertigo	3/321 (0.9%)		0/137 (0%)		0/49 (0%)
Eye disorders
Catarac	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Diplopia	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Gastrointestinal disorders
Pancreatitis	6/321 (1.9%)		0/137 (0%)		0/49 (0%)
Abdominal pain	4/321 (1.2%)		3/137 (2.2%)		0/49 (0%)
Vomiting	3/321 (0.9%)		0/137 (0%)		0/49 (0%)
Diarrhoea	2/321 (0.6%)		2/137 (1.5%)		0/49 (0%)
Nausea	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Gastric ulcer	0/321 (0%)		0/137 (0%)		1/49 (2%)
Gastrointestinal haemorrhage	0/321 (0%)		0/137 (0%)		1/49 (2%)
General disorders
Pyrexia	9/321 (2.8%)		6/137 (4.4%)		2/49 (4.1%)
Chest pain	4/321 (1.2%)		0/137 (0%)		0/49 (0%)
Malaise	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Asthenia	0/321 (0%)		0/137 (0%)		0/49 (0%)
Hepatobiliary disorders
Cholelithiasis	3/321 (0.9%)		0/137 (0%)		1/49 (2%)
Infections and infestations
Lower respiratory tract infection	4/321 (1.2%)		0/137 (0%)		0/49 (0%)
Cellulitis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Peritonitis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Pneumonia	2/321 (0.6%)		7/137 (5.1%)		4/49 (8.2%)
Sepsis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Urinary tract infection	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Abdominal abscess	0/321 (0%)		0/137 (0%)		1/49 (2%)
Erysipelas	0/321 (0%)		0/137 (0%)		1/49 (2%)
Herpes zoster	0/321 (0%)		0/137 (0%)		0/49 (0%)
Injury, poisoning and procedural complications
Subdural haemorrhage	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Hip fracture	0/321 (0%)		0/137 (0%)		1/49 (2%)
Nerve injury	0/321 (0%)		0/137 (0%)		1/49 (2%)
Investigations
Lipase increased	3/321 (0.9%)		2/137 (1.5%)		0/49 (0%)
White blood cell count increased	0/321 (0%)		3/137 (2.2%)		2/49 (4.1%)
Electrocardiogram QT prolonged	0/321 (0%)		0/137 (0%)		1/49 (2%)
Haemoglobin decreased	0/321 (0%)		0/137 (0%)		1/49 (2%)
Metabolism and nutrition disorders
Hyperglycaemia	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Dehydration	0/321 (0%)		0/137 (0%)		1/49 (2%)
Musculoskeletal and connective tissue disorders
Bone pain	4/321 (1.2%)		3/137 (2.2%)		0/49 (0%)
Pain in extremity	4/321 (1.2%)		0/137 (0%)		0/49 (0%)
Arthralgia	3/321 (0.9%)		0/137 (0%)		0/49 (0%)
Intervertebral disc protrusion	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Muscular weakness	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Musculoskeletal chest pain	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Flank pain	0/321 (0%)		0/137 (0%)		1/49 (2%)
Intervertebral disc disorder	0/321 (0%)		0/137 (0%)		1/49 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Back pain	4/321 (1.2%)		0/137 (0%)		1/49 (2%)
Prostate cancer	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Prostatic adenoma	0/321 (0%)		0/137 (0%)		1/49 (2%)
Rectal adenocarcinoma	0/321 (0%)		0/137 (0%)		1/49 (2%)
Nervous system disorders
Cerebrovascular accident	4/321 (1.2%)		0/137 (0%)		0/49 (0%)
Dizziness	4/321 (1.2%)		0/137 (0%)		0/49 (0%)
Brain oedema	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Cerebral infarction	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Cerebral ischaemia	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Headache	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Loss of consciousness	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Peripheral sensory neuropathy	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Presyncope	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Cerebral haemorrhage	0/321 (0%)		3/137 (2.2%)		1/49 (2%)
Aphasia	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Syncope	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Renal and urinary disorders
Renal failure	3/321 (0.9%)		0/137 (0%)		1/49 (2%)
Urinary retention	0/321 (0%)		0/137 (0%)		1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	5/321 (1.6%)		3/137 (2.2%)		0/49 (0%)
Pleural effusion	4/321 (1.2%)		0/137 (0%)		0/49 (0%)
Interstitial lung disease	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Pleurisy	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Pulmonary oedema	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Pneumonitis	0/321 (0%)		2/137 (1.5%)		1/49 (2%)
Respiratory failure	0/321 (0%)		2/137 (1.5%)		0/49 (0%)
Cough	0/321 (0%)		0/137 (0%)		5/49 (10.2%)
Productive cough	0/321 (0%)		0/137 (0%)		1/49 (2%)
Skin and subcutaneous tissue disorders
Skin necrosis	0/321 (0%)		0/137 (0%)		1/49 (2%)
Vascular disorders
Deep vein thrombosis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Haematoma	2/321 (0.6%)		0/137 (0%)		1/49 (2%)
Temporal arteritis	2/321 (0.6%)		0/137 (0%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	CML-CP With Prior Imatinib Only		CML-AP With Prior Imatinib Only		CML-CP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	319/321 (99.4%)		136/137 (99.3%)		48/49 (98%)
Blood and lymphatic system disorders
Thrombocytopenia	107/321 (33.3%)		60/137 (43.8%)		16/49 (32.7%)
Anaemia	71/321 (22.1%)		61/137 (44.5%)		9/49 (18.4%)
Neutropenia	57/321 (17.8%)		39/137 (28.5%)		15/49 (30.6%)
Leukopenia	16/321 (5%)		11/137 (8%)		3/49 (6.1%)
Thrombocytosis	16/321 (5%)		0/137 (0%)		0/49 (0%)
Lymphadenopathy	0/321 (0%)		7/137 (5.1%)		0/49 (0%)
Febrile neutropenia	0/321 (0%)		7/137 (5.1%)		0/49 (0%)
Leukocytosis	0/321 (0%)		9/137 (6.6%)		0/49 (0%)
Cardiac disorders
Tachycardia	0/321 (0%)		7/137 (5.1%)		0/49 (0%)
Ventricular extrasystoles	0/321 (0%)		0/137 (0%)		3/49 (6.1%)
Eye disorders
Conjunctivitis	20/321 (6.2%)		0/137 (0%)		0/49 (0%)
Gastrointestinal disorders
Nausea	121/321 (37.7%)		41/137 (29.9%)		13/49 (26.5%)
Diarrhoea	93/321 (29%)		34/137 (24.8%)		6/49 (12.2%)
Vomiting	92/321 (28.7%)		30/137 (21.9%)		7/49 (14.3%)
Constipation	88/321 (27.4%)		31/137 (22.6%)		10/49 (20.4%)
Abdominal pain	47/321 (14.6%)		17/137 (12.4%)		8/49 (16.3%)
Abdominal pain upper	46/321 (14.3%)		21/137 (15.3%)		6/49 (12.2%)
Dyspepsia	33/321 (10.3%)		0/137 (0%)		7/49 (14.3%)
Stomatitis	0/321 (0%)		14/137 (10.2%)		3/49 (6.1%)
Haemorrhoids	0/321 (0%)		7/137 (5.1%)		3/49 (6.1%)
General disorders
Fatigue	105/321 (32.7%)		28/137 (20.4%)		13/49 (26.5%)
Pyrexia	66/321 (20.6%)		49/137 (35.8%)		8/49 (16.3%)
Oedema peripheral	55/321 (17.1%)		27/137 (19.7%)		5/49 (10.2%)
Asthenia	53/321 (16.5%)		24/137 (17.5%)		12/49 (24.5%)
Chest pain	19/321 (5.9%)		0/137 (0%)		4/49 (8.2%)
Pain	19/321 (5.9%)		10/137 (7.3%)		4/49 (8.2%)
Chills	0/321 (0%)		15/137 (10.9%)		1/49 (2%)
Inflammation	0/321 (0%)		0/137 (0%)		3/49 (6.1%)
Hepatobiliary disorders
Hyperbilirubinaemia	32/321 (10%)		10/137 (7.3%)		0/49 (0%)
Hyperbilirubinaemia	0/321 (0%)		0/137 (0%)		4/49 (8.2%)
Infections and infestations
Nasopharyngitis	80/321 (24.9%)		0/137 (0%)		0/49 (0%)
Upper respiratory tract infection	41/321 (12.8%)		7/137 (5.1%)		5/49 (10.2%)
Urinary tract infection	28/321 (8.7%)		0/137 (0%)		4/49 (8.2%)
Bronchitis	26/321 (8.1%)		0/137 (0%)		4/49 (8.2%)
Sinusitis	22/321 (6.9%)		0/137 (0%)		5/49 (10.2%)
Influenza	21/321 (6.5%)		0/137 (0%)		0/49 (0%)
Rhinitis	16/321 (5%)		0/137 (0%)		3/49 (6.1%)
Pneumonia	0/321 (0%)		7/137 (5.1%)		3/49 (6.1%)
Nasopharyngitis	0/321 (0%)		0/137 (0%)		8/49 (16.3%)
Herpes simplex	0/321 (0%)		0/137 (0%)		3/49 (6.1%)
Herpes zoster	0/321 (0%)		0/137 (0%)		3/49 (6.1%)
Periodontitis	0/321 (0%)		0/137 (0%)		3/49 (6.1%)
Injury, poisoning and procedural complications
Procedural pain	17/321 (5.3%)		0/137 (0%)		0/49 (0%)
Investigations
Lipase increased	55/321 (17.1%)		8/137 (5.8%)		10/49 (20.4%)
Alanine aminotransferase increased	39/321 (12.1%)		14/137 (10.2%)		8/49 (16.3%)
Weight decreased	30/321 (9.3%)		15/137 (10.9%)		2/49 (4.1%)
Blood bilirubin increased	29/321 (9%)		14/137 (10.2%)		4/49 (8.2%)
Aspartate aminotransferase increased	24/321 (7.5%)		7/137 (5.1%)		5/49 (10.2%)
Blood creatine phosphokinase increased	19/321 (5.9%)		0/137 (0%)		3/49 (6.1%)
Gamma-glutamyltransferase increased	19/321 (5.9%)		0/137 (0%)		0/49 (0%)
Amylase increased	18/321 (5.6%)		0/137 (0%)		3/49 (6.1%)
White blood cell count decreased	0/321 (0%)		11/137 (8%)		0/49 (0%)
Haemoglobin decreased	0/321 (0%)		9/137 (6.6%)		0/49 (0%)
Haemoglobin decreased	0/321 (0%)		7/137 (5.1%)		0/49 (0%)
Platelet count decreased	0/321 (0%)		7/137 (5.1%)		0/49 (0%)
Weight increased	0/321 (0%)		0/137 (0%)		5/49 (10.2%)
Blood glucose increased	0/321 (0%)		0/137 (0%)		4/49 (8.2%)
Metabolism and nutrition disorders
Decreased appetite	50/321 (15.6%)		12/137 (8.8%)		7/49 (14.3%)
Hyperglycaemia	27/321 (8.4%)		12/137 (8.8%)		3/49 (6.1%)
Hypokalaemia	25/321 (7.8%)		22/137 (16.1%)		6/49 (12.2%)
Hypophosphataemia	22/321 (6.9%)		10/137 (7.3%)		5/49 (10.2%)
Hypomagnesaemia	19/321 (5.9%)		10/137 (7.3%)		0/49 (0%)
Hypocalcaemia	17/321 (5.3%)		15/137 (10.9%)		0/49 (0%)
Hyperkalaemia	0/321 (0%)		0/137 (0%)		3/49 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	86/321 (26.8%)		20/137 (14.6%)		10/49 (20.4%)
Myalgia	63/321 (19.6%)		0/137 (0%)		7/49 (14.3%)
Pain in extremity	63/321 (19.6%)		18/137 (13.1%)		9/49 (18.4%)
Back pain	60/321 (18.7%)		19/137 (13.9%)		7/49 (14.3%)
Muscle spasms	45/321 (14%)		9/137 (6.6%)		8/49 (16.3%)
Bone pain	43/321 (13.4%)		14/137 (10.2%)		4/49 (8.2%)
Musculoskeletal pain	32/321 (10%)		0/137 (0%)		3/49 (6.1%)
Neck pain	16/321 (5%)		0/137 (0%)		3/49 (6.1%)
Musculoskeletal chest pain	0/321 (0%)		7/137 (5.1%)		1/49 (2%)
Nervous system disorders
Headache	114/321 (35.5%)		0/137 (0%)		11/49 (22.4%)
Dizziness	35/321 (10.9%)		0/137 (0%)		5/49 (10.2%)
Paraesthesia	17/321 (5.3%)		0/137 (0%)		0/49 (0%)
Psychiatric disorders
Insomnia	40/321 (12.5%)		0/137 (0%)		2/49 (4.1%)
Depression	28/321 (8.7%)		0/137 (0%)		3/49 (6.1%)
Anxiety	20/321 (6.2%)		0/137 (0%)		3/49 (6.1%)
Renal and urinary disorders
Pollakiuria	17/321 (5.3%)		0/137 (0%)		0/49 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	91/321 (28.3%)		21/137 (15.3%)		0/49 (0%)
Dyspnoea	51/321 (15.9%)		14/137 (10.2%)		9/49 (18.4%)
Oropharyngeal pain	39/321 (12.1%)		16/137 (11.7%)		2/49 (4.1%)
Dyspnoea exertional	21/321 (6.5%)		0/137 (0%)		0/49 (0%)
Epistaxis	16/321 (5%)		17/137 (12.4%)		2/49 (4.1%)
Skin lesion	19/321 (5.9%)		0/137 (0%)		3/49 (6.1%)
Pleural effusion	0/321 (0%)		10/137 (7.3%)		4/49 (8.2%)
Skin and subcutaneous tissue disorders
Rash	118/321 (36.8%)		39/137 (28.5%)		20/49 (40.8%)
Pruritus	104/321 (32.4%)		18/137 (13.1%)		9/49 (18.4%)
Night sweats	37/321 (11.5%)		7/137 (5.1%)		3/49 (6.1%)
Dry skin	36/321 (11.2%)		0/137 (0%)		4/49 (8.2%)
Alopecia	34/321 (10.6%)		8/137 (5.8%)		1/49 (2%)
Erythema	30/321 (9.3%)		0/137 (0%)		4/49 (8.2%)
Hyperhidrosis	26/321 (8.1%)		7/137 (5.1%)		3/49 (6.1%)
Petechiae	0/321 (0%)		9/137 (6.6%)		0/49 (0%)
Vascular disorders
Hypertension	37/321 (11.5%)		0/137 (0%)		5/49 (10.2%)
Haematoma	0/321 (0%)		10/137 (7.3%)		0/49 (0%)
Hypotension	0/321 (0%)		10/137 (7.3%)		1/49 (2%)

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.