Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01698905
• Collaborator: (none)
• Enrollment: 163
• Locations: 62
• Arm: 1
• Anticipated Duration (Months): 145.6
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: nilotinib	Phase 2

Detailed Description

The Primary objective was to evaluate the proportion of patients in TFR within 48 weeks following nilotinib cessation.

This study originally consisted of seven phases (five treatment phases and two treatment-free phases) from which two were the focus of this primary analysis report (consolidation, TFR and treatment re-initiation) The study consisted of 2 main phases: Consolidation and TFR

Nilotinib treatment consolidation phase (NTCS): Patients who satisfied all inclusion/exclusion criteria were enrolled in the consolidation phase and continued to receive nilotinib for 52 weeks at the dose which the patient was receiving prior to study entry. If a patient maintained MR4.5 throughout the consolidation phase, he/she was eligible to enter in the TFR phase. If a patient had confirmed loss of MR4.5 during the consolidation phase, he/she was not eligible to enter in the TFR phase and continued nilotinib treatment.

Nilotinib TFR phase: Patients who were eligible to enter in the TFR phase after completing the 52 week consolidation phase stopped taking nilotinib on the first day of the TFR phase. Duration of this phase was up to 520 weeks after the last patient enters in the TFR phase.

Nilotinib treatment re-initiation phase (NTRI): If a patient had a confirmed loss of MR4 (two consecutive BCR-ABL >0.01% IS) or loss of MMR (BCR-ABL >0.1% IS) in the TFR phase, the patient restarted nilotinib treatment. Patients will be on nilotinib treatment for up to 520 weeks after the last patient entered the nilotinib TFR phase, or until a patient experience unacceptable toxicity, disease progression and/or treatment discontinued at the discretion of the Investigator or if the patient withdrew consent. Nilotinib cessation was not attempted for a second time in the patient who reinitiated treatment or discontinued following the TFR phase.

Nilotinib treatment continuation phase (NTCT) and Nilotinib treatment prolonged continuation phase (NTCT-P): Patients who were not eligible to enter into the TFR phase after completing the 52-week NTCS phase entered the nilotinib treatment continuation (NTCT) phase and would continue treatment with nilotinib for another 52 weeks (a total of 104 weeks of treatment). Patients who were not able to maintain MR4.5 and had a confirmed loss of MR4.5 during the NTCT phase were not eligible to enter the TFR-2 phase. These patients entered into the nilotinib prolonged treatment continuation phase (NTCT-P) and continued nilotinib treatment until 520 weeks after the last patient entered the nilotinib TFR phase, or until the patients experience unacceptable toxicity, disease progression and/or treatment would be discontinued at the discretion of the Investigator or withdrawal of consent.

Nilotinib TFR-2 phase: Patients who maintained MR4.5 during the NTCT phase were eligible to cease nilotinib treatment and enter the TFR-2 phase. The duration of the nilotinib TFR-2 phase is up to 520 weeks after the last patient entered the TFR phase. Patients stopped taking nilotinib therapy on the day they entered the TFR-2 phase.

Nilotinib treatment re-initiation-2 (NTRI-2): If a patient had a loss of MMR or a confirmed loss of MR4 during the TFR-2 phase, he/she entered the nilotinib treatment re-initiation-2 (NTRI-2) phase and resumed nilotinib treatment at a dose of either 300 mg or 400 mg bid.

Safety follow-up was performed within 30 days after the last dose of study treatment or the last day in TFR/TFR-2.

Post-treatment follow-up visits were performed every 12 weeks up to 520 weeks after the last patient entered the nilotinib TFR phase.

Study Design

• Study Type: Interventional
• Actual Enrollment: 163 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib
• Actual Study Start Date: Dec 20, 2012
• Actual Primary Completion Date: Nov 26, 2015
• Anticipated Study Completion Date: Feb 6, 2025

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Nilotinib Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening

Drug: nilotinib; Nilotinib was dosed by weight or body surface area. Nilotinib 300 mg BID or 400 mg BID was be administered orally at approximately 12 hour intervals, and must not have been taken with food. The capsules were to be swallowed whole with water. No food should have been consumed for at least 2 hours before the dose was taken and no additional food should have been consumed for at least one hour after the dose was taken. Patients were also allowed to enter this study on the same dose they were taking prior to study entry. Patients who required permanent dose reduction from their original starting dose were to be allowed to enter this study on the same dose only if the patient maintained this dose for a minimum of 6 months prior to study entry.; Other Names: AMN107

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients in Treatment Free Remission (TFR) Within 48 Weeks [First 48 weeks following nilotinib cessation.]

   TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 48 weeks after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, and multiplied by 100.

Secondary Outcome Measures

1. Percentage of Patients in Treatment Free Remission (TFR) Within 96, 144, 192, 264 Weeks and Within 6,7,8,9 and 10 Years [96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessation]

   TFR is defined as no confirmed loss of MR4 (molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, multiplied by 100.

2. Progression Free Survival (PFS) to Accelerated Phase/Blast Crisis (AP/BC) or Death [nilotinib cessation up to approximately 580 weeks]

   Kaplan-Meier (KM) estimation of PFS. PFS is measured from the date of start of nilotinib TFR phase (cessation of nilotinib) to the date of the earliest of the event: progression to AP/BC, or death from any cause. Patients not known to have recurred or died on or before the cut-off date for the KM analysis will have their PFS interval right-censored at the earlier of the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up.

3. Treatment Free Survival (TFS) [nilotinib cessation up to approximately 580 weeks]

   Kaplan-Meier (KM) estimation of TFS is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4, re-start of nilotinib treatment, progression to AP/BC or death from any cause. Patients not known to have had any of the events or died on or before the cut-off date for the KM analysis will have their TFS interval right-censored at the earlier of the date of their last assessment (PCR, cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up. A TFS sensitivity analysis will be conducted by considering discontinuation from TFR phase due to any reason as an event, in addition to the events as defined above

4. Overall Survival (OS) [nilotinib cessation up to approximately 580 weeks]

   Kaplan-Meier (KM) estimation of OS. OS is measured from the date of start of nilotinib TFR phase to the date of death from any cause. If a patient is not known to have died, survival will be censored at the date of last contact.

5. Change in BCR-ABL (Oncoprotein Product of BCR-ABL Fusion Gene) Transcripts After Re-start of Nilotinib Therapy [re-start of nilotinib up to approximately 48 weeks]

   Descriptive statistics of BCR-ABL over time after re-start of nilotinib therapy. ABL= Abelson leukemia virus and BCR=Break point cluster region

6. Percentage of Patients With Stable MMR in Nilotinib Re-initiation Phase [start of nilotinib in re-initiation phase up to approximately 432 weeks]

   Percentage of patients who are in stable MMR (stable MMR=BCR-ABL ≤ 0.1% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MMR any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MMR, irrespective of whether there is loss of MMR in between, by the number of patients who achieved MMR at any time during the nilotinib re-initiation phase, and multiplied by 100.

7. Percentage of Patients With Stable MR4 in Nilotinib Re-initiation Phase [start of nilotinib in re-initiation phase up to approximately 432 weeks]

   Percentage of patients who are in stable MR4 (stable MR4=BCR-ABL ≤ 0.01% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MR4, irrespective of whether there is loss of MR4 in between, by the number of patients who achieved MR4 at any time during the nilotinib re-initiation phase, and multiplied by 100.

8. Percentage of Patients With Stable MR4.5 in Nilotinib Re-initiation Phase [start of nilotinib in re-initiation phase up to approximately 432 weeks]

   Percentage of patients who are in stable MR4.5 (stable MR4.5=BCR-ABL ≤ 0.0032% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4.5 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MR4.5, irrespective of whether there is loss of MR4.5 in between, by the number of patients who achieved MR4.5 at any time during the nilotinib re-initiation phase, multiplied by 100.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male or female patients >= 18 years of age

2. ECOG Performance Status of 0, 1, or 2

3. Patient with diagnosis of BCR-ABL positive CML CP

4. Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib (> 4 weeks) and then switched to nilotinib) since initial diagnosis

5. Patient has at least 2 years of nilotinib treatment prior to study entry.

6. Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening

7. Adequate end organ function as defined by:

• Direct bilirubin ≤ 1.5 x ULN except for i) patient with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range)

• SGOT(AST) and SGPT(ALT) < 3 x ULN (upper limit of normal)

• Serum lipase ≤ 2 x ULN

• Alkaline phosphatase ≤ 2.5 x ULN

• Serum creatinine < 1.5 x ULN

1. Patients must have the following electrolyte values ≥ LLN (lower limit of normal) limits or corrected to within normal limits with supplements prior to the first dose of study medication:

• Potassium

• Magnesium

• Total calcium (corrected for serum albumin)

1. Patients must have normal marrow function as defined below:

• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L

• Platelets ≥ 100 x 109/L

• Hemoglobin ≥ 9.0 g/dL

1. Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

1. Prior AP, BC or allo-transplant

2. Patient has documented MR4.5 at the time when switched from imatinib to nilotinib

3. Patients with known atypical transcript

4. CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past)

5. Dose reductions due to neutropenia or thrombocytopenia in the past 6 months

6. Patient ever attempted to permanently discontinue imatinib or nilotinib treatment

7. Known impaired cardiac function including any one of the following:

• Inability to determine the QT interval on ECG

• Complete left bundle branch block

• Long QT syndrome or a known family history of long QT syndrome

• History of or presence of clinically significant ventricular or atrial tachyarrhythmias

• Clinically significant resting bradycardia

• QTcF > 480 msec

• History or clinical signs of myocardial infarction within 1 year prior to study entry

• History of unstable angina within 1 year prior to study entry

• Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension)

1. Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection)

2. History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis

3. Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer

4. History of other active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ treated curatively

5. Patients who have not recovered from prior surgery

6. Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1

7. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. See Appendix 14.1 for a list of these medications. This list may not be comprehensive.

8. Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo.

9. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to study entry. (Please see www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents that prolong the QT interval.)

10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)

11. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.

12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test before initiation of study treatment and must also use highly effective methods of contraception while enrolled in the study. The use of highly effective contraception should continue for at least 14 days after the last dose of study treatment or until the last day of TFR/TFR-2, or for the duration of a monthly cycle of oral contraception, whichever is longer. Acceptable forms of highly effective contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

• Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception, women should be stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks prior to enrolling. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If a study patient becomes pregnant or is suspected of being pregnant during the study or within 30 days as part of safety evaluations after the final dose of nilotinib, the Study Doctor needs to be informed immediately and any ongoing study treatment with nilotinib has to be stopped immediately.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC Kenneth Norris Comprehensive Cancer Center USC	Los Angeles	California	United States	90033
2	Indiana Blood and Marrow Institute SC	Beech Grove	Indiana	United States	46107
3	St. Agnes Hospital SC	Baltimore	Maryland	United States	21229
4	University of Texas Medical Branch SC	Galveston	Texas	United States	77555-1188
5	Compass Oncology	Vancouver	Washington	United States	98683
6	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1221ADC
7	Novartis Investigative Site	Buenos Aires		Argentina	C1114AAN
8	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
9	Novartis Investigative Site	Box Hill	Victoria	Australia	3128
10	Novartis Investigative Site	Antwerp		Belgium	2060
11	Novartis Investigative Site	Goiania	GO	Brazil	74605-050
12	Novartis Investigative Site	Belo Horizonte	MG	Brazil	30130-100
13	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	20.211-030
14	Novartis Investigative Site	Rio De Janiero	RJ	Brazil	20231-050
15	Novartis Investigative Site	Porto Alegre	RS	Brazil	90035-003
16	Novartis Investigative Site	Campinas	SP	Brazil
17	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
18	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
19	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
20	Novartis Investigative Site	Quebec		Canada	G1J 1Z4
21	Novartis Investigative Site	Bordeaux		France	33076
22	Novartis Investigative Site	Grenoble		France	38043
23	Novartis Investigative Site	Lyon Cedex		France	69373
24	Novartis Investigative Site	Strasbourg cedex		France	67085
25	Novartis Investigative Site	Vandoeuvre les Nancy		France	54511
26	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg	Germany	68305
27	Novartis Investigative Site	Berlin		Germany	13353
28	Novartis Investigative Site	Heilbronn		Germany	74072
29	Novartis Investigative Site	Potsdam		Germany	14467
30	Novartis Investigative Site	Ulm		Germany	89081
31	Novartis Investigative Site	Larissa	GR	Greece	411 10
32	Novartis Investigative Site	Athens		Greece	106 76
33	Novartis Investigative Site	Athens		Greece	18547
34	Novartis Investigative Site	Haifa		Israel	3109601
35	Novartis Investigative Site	Petach Tikva		Israel	4910002
36	Novartis Investigative Site	Ramat Gan		Israel	52621
37	Novartis Investigative Site	Nagoya	Aichi	Japan	464 8681
38	Novartis Investigative Site	Narita	Chiba	Japan	286-8523
39	Novartis Investigative Site	Fukuoka city	Fukuoka	Japan	812-8582
40	Novartis Investigative Site	Kurume city	Fukuoka	Japan	830-0011
41	Novartis Investigative Site	Akita		Japan	010-8543
42	Novartis Investigative Site	Aomori		Japan	030 8553
43	Novartis Investigative Site	Chiba		Japan	260 8677
44	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
45	Novartis Investigative Site	Monterrey	Nuevo Leon	Mexico	64718
46	Novartis Investigative Site	Krakow	Malopolskie	Poland	30-510
47	Novartis Investigative Site	Gdansk		Poland	80-952
48	Novartis Investigative Site	Warszawa		Poland	02 776
49	Novartis Investigative Site	Moscow		Russian Federation	125167
50	Novartis Investigative Site	St Petersburg		Russian Federation	191024
51	Novartis Investigative Site	St Petersburg		Russian Federation	197341
52	Novartis Investigative Site	Singapore		Singapore	169608
53	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
54	Novartis Investigative Site	Santander	Cantabria	Spain	39008
55	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
56	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
57	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife	Spain	38320
58	Novartis Investigative Site	Madrid		Spain	28006
59	Novartis Investigative Site	Madrid		Spain	28034
60	Novartis Investigative Site	Madrid		Spain	28046
61	Novartis Investigative Site	Liverpool		United Kingdom	L7 8XP
62	Novartis Investigative Site	Nottingham		United Kingdom	NG5

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: NCT01698905
• Other Study ID Numbers: CAMN107A2408; 2012-003186-18
• First Posted: Oct 3, 2012
• Last Update Posted: Mar 21, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: AMN107; CML; Phase II; single arm; open label; nilotinib; treatment-free remission; MR4.5; confirmed loss of MR4; loss of MMR; Ph+ CML-CP
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Results

Participant Flow

Recruitment Details	A total of 163 patients were enrolled into this study. 126 of the 163 patients who completed 52 weeks of nilotinib treatment in the NTCS phase entered the TFR phase and were part of the Full analysis Set (FAS).
Pre-assignment Detail	Approximately 117 patients were planned to be enrolled into this study.

Arm/Group Title	NTCS Phase
Arm/Group Description	Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
Period Title: Overall Study
STARTED	163
Still on Study Phase	0
TFR Phase	126
NTRI Phase	51
NTCT Phase	26
TFR-2 Phase	2
NTRI-2 Phase	1
NTCT-P Phase Phase	6
COMPLETED	152
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	NTCS Phase
Arm/Group Description	Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
Overall Participants	163
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.3 (13.99)
Sex: Female, Male (Count of Participants)
Female	86 52.8%
Male	77 47.2%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	127 77.9%
Black	6 3.7%
Asian	23 14.1%
Native American	1 0.6%
Other	6 3.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients in Treatment Free Remission (TFR) Within 48 Weeks
Description	TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 48 weeks after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, and multiplied by 100.
Time Frame	First 48 weeks following nilotinib cessation.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): FAS included all patients who entered the TFR phase.

Arm/Group Title	NTCS Phase
Arm/Group Description	Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
Measure Participants	126
Number (95% Confidence Interval) [Percentage of participants]	57.9 35.5%

2. Secondary Outcome

Title	Percentage of Patients in Treatment Free Remission (TFR) Within 96, 144, 192, 264 Weeks and Within 6,7,8,9 and 10 Years
Description	TFR is defined as no confirmed loss of MR4 (molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation. Percentage of patients in TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, no documented loss of MMR and no re-starting of nilotinib therapy in the first 96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase, multiplied by 100.
Time Frame	96, 144, 192, 264 weeks and within 6,7,8,9 and 10 years following nilotinib cessation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Progression Free Survival (PFS) to Accelerated Phase/Blast Crisis (AP/BC) or Death
Description	Kaplan-Meier (KM) estimation of PFS. PFS is measured from the date of start of nilotinib TFR phase (cessation of nilotinib) to the date of the earliest of the event: progression to AP/BC, or death from any cause. Patients not known to have recurred or died on or before the cut-off date for the KM analysis will have their PFS interval right-censored at the earlier of the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up.
Time Frame	nilotinib cessation up to approximately 580 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Treatment Free Survival (TFS)
Description	Kaplan-Meier (KM) estimation of TFS is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4, re-start of nilotinib treatment, progression to AP/BC or death from any cause. Patients not known to have had any of the events or died on or before the cut-off date for the KM analysis will have their TFS interval right-censored at the earlier of the date of their last assessment (PCR, cytogenetic, hematology or extramedullary) for patients who are still on study and at the date of last contact for patients are in follow-up. A TFS sensitivity analysis will be conducted by considering discontinuation from TFR phase due to any reason as an event, in addition to the events as defined above
Time Frame	nilotinib cessation up to approximately 580 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Kaplan-Meier (KM) estimation of OS. OS is measured from the date of start of nilotinib TFR phase to the date of death from any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
Time Frame	nilotinib cessation up to approximately 580 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change in BCR-ABL (Oncoprotein Product of BCR-ABL Fusion Gene) Transcripts After Re-start of Nilotinib Therapy
Description	Descriptive statistics of BCR-ABL over time after re-start of nilotinib therapy. ABL= Abelson leukemia virus and BCR=Break point cluster region
Time Frame	re-start of nilotinib up to approximately 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Percentage of Patients With Stable MMR in Nilotinib Re-initiation Phase
Description	Percentage of patients who are in stable MMR (stable MMR=BCR-ABL ≤ 0.1% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MMR any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MMR, irrespective of whether there is loss of MMR in between, by the number of patients who achieved MMR at any time during the nilotinib re-initiation phase, and multiplied by 100.
Time Frame	start of nilotinib in re-initiation phase up to approximately 432 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Percentage of Patients With Stable MR4 in Nilotinib Re-initiation Phase
Description	Percentage of patients who are in stable MR4 (stable MR4=BCR-ABL ≤ 0.01% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MR4, irrespective of whether there is loss of MR4 in between, by the number of patients who achieved MR4 at any time during the nilotinib re-initiation phase, and multiplied by 100.
Time Frame	start of nilotinib in re-initiation phase up to approximately 432 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Percentage of Patients With Stable MR4.5 in Nilotinib Re-initiation Phase
Description	Percentage of patients who are in stable MR4.5 (stable MR4.5=BCR-ABL ≤ 0.0032% IS) at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after achievement of that response in the nilotinib re-initiation phase for 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks is calculated by dividing the number of patients achieving MR4.5 any time during the nilotinib re-initiation phase and having the same response at 48, 96, 144, 192, 240, 288, 336, 384, and 432 weeks after the first achievement of MR4.5, irrespective of whether there is loss of MR4.5 in between, by the number of patients who achieved MR4.5 at any time during the nilotinib re-initiation phase, multiplied by 100.
Time Frame	start of nilotinib in re-initiation phase up to approximately 432 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until 30 days after the last dose of study treatment or the last day in the TFR/TFR-2 phase for approx. 35 months.
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment plus 30 days post treatment.
Arm/Group Title	NTCS Phase		TFR Phase		NTRI Phase		NTCT Phase		TFR-2 Phase		NTRI-2 Phase		NTCT-P Phase		All Patients
Arm/Group Description	Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening		treatment-free remission		nilotinib treatment re-initiation		nilotinib treatment continuation		treatment-free remission 2		nilotinib treatment re-initiation 2		nilotinib treatment prolonged continuation		All patients enrolled in the study
All Cause Mortality
	NTCS Phase		TFR Phase		NTRI Phase		NTCT Phase		TFR-2 Phase		NTRI-2 Phase		NTCT-P Phase		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Serious Adverse Events
	NTCS Phase		TFR Phase		NTRI Phase		NTCT Phase		TFR-2 Phase		NTRI-2 Phase		NTCT-P Phase		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/163 (12.9%)		8/126 (6.3%)		4/51 (7.8%)		3/26 (11.5%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		34/163 (20.9%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	2/163 (1.2%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		2/163 (1.2%)
ARRHYTHMIA	0/163 (0%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
ATRIAL FIBRILLATION	2/163 (1.2%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		2/163 (1.2%)
ATRIOVENTRICULAR BLOCK	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
CARDIAC FAILURE CONGESTIVE	0/163 (0%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
CORONARY ARTERY DISEASE	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
SINUS TACHYCARDIA	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Gastrointestinal disorders
CONSTIPATION	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
DIARRHOEA	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
INTESTINAL OBSTRUCTION	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
General disorders
NECROSIS	0/163 (0%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Infections and infestations
CELLULITIS	1/163 (0.6%)		2/126 (1.6%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		3/163 (1.8%)
DIVERTICULITIS	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
GASTROENTERITIS	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
INFLUENZA	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
PNEUMONIA	2/163 (1.2%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		3/163 (1.8%)
POST PROCEDURAL INFECTION	0/163 (0%)		0/126 (0%)		0/51 (0%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Injury, poisoning and procedural complications
LIGAMENT SPRAIN	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Investigations
HAEMATOLOGY TEST ABNORMAL	0/163 (0%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
TRANSAMINASES INCREASED	0/163 (0%)		0/126 (0%)		0/51 (0%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Metabolism and nutrition disorders
TYPE 2 DIABETES MELLITUS	0/163 (0%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
MUSCLE SPASMS	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
PAIN IN EXTREMITY	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA	0/163 (0%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
LUNG ADENOCARCINOMA	0/163 (0%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
LYMPHOPROLIFERATIVE DISORDER	0/163 (0%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
PROSTATE CANCER	0/163 (0%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
URETERIC CANCER	0/163 (0%)		0/126 (0%)		0/51 (0%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Nervous system disorders
CARPAL TUNNEL SYNDROME	0/163 (0%)		1/126 (0.8%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
CEREBRAL INFARCTION	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
CEREBROVASCULAR ACCIDENT	0/163 (0%)		0/126 (0%)		0/51 (0%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
ISCHAEMIC STROKE	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Renal and urinary disorders
RENAL FAILURE	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Reproductive system and breast disorders
METRORRHAGIA	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
DYSPNOEA EXERTIONAL	0/163 (0%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
PLEURAL FIBROSIS	0/163 (0%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
Vascular disorders
ARTERIAL HAEMORRHAGE	1/163 (0.6%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		1/163 (0.6%)
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	2/163 (1.2%)		0/126 (0%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		3/163 (1.8%)
Other (Not Including Serious) Adverse Events
	NTCS Phase		TFR Phase		NTRI Phase		NTCT Phase		TFR-2 Phase		NTRI-2 Phase		NTCT-P Phase		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/163 (49.1%)		70/126 (55.6%)		29/51 (56.9%)		11/26 (42.3%)		0/2 (0%)		0/1 (0%)		2/6 (33.3%)		122/163 (74.8%)
Blood and lymphatic system disorders
ANAEMIA	2/163 (1.2%)		2/126 (1.6%)		1/51 (2%)		2/26 (7.7%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		6/163 (3.7%)
Gastrointestinal disorders
ABDOMINAL PAIN	6/163 (3.7%)		2/126 (1.6%)		2/51 (3.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		10/163 (6.1%)
ABDOMINAL PAIN LOWER	0/163 (0%)		0/126 (0%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)		1/163 (0.6%)
ABDOMINAL PAIN UPPER	3/163 (1.8%)		3/126 (2.4%)		1/51 (2%)		2/26 (7.7%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		9/163 (5.5%)
CONSTIPATION	5/163 (3.1%)		0/126 (0%)		3/51 (5.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		8/163 (4.9%)
DIARRHOEA	4/163 (2.5%)		5/126 (4%)		1/51 (2%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		11/163 (6.7%)
NAUSEA	5/163 (3.1%)		2/126 (1.6%)		4/51 (7.8%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		9/163 (5.5%)
General disorders
FATIGUE	6/163 (3.7%)		3/126 (2.4%)		3/51 (5.9%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		12/163 (7.4%)
Infections and infestations
NASOPHARYNGITIS	10/163 (6.1%)		5/126 (4%)		3/51 (5.9%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		14/163 (8.6%)
UPPER RESPIRATORY TRACT INFECTION	7/163 (4.3%)		2/126 (1.6%)		3/51 (5.9%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		11/163 (6.7%)
Investigations
WEIGHT INCREASED	0/163 (0%)		11/126 (8.7%)		0/51 (0%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		11/163 (6.7%)
Metabolism and nutrition disorders
DECREASED APPETITE	2/163 (1.2%)		0/126 (0%)		3/51 (5.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		4/163 (2.5%)
HYPERTRIGLYCERIDAEMIA	1/163 (0.6%)		1/126 (0.8%)		3/51 (5.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		3/163 (1.8%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	8/163 (4.9%)		30/126 (23.8%)		6/51 (11.8%)		2/26 (7.7%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		43/163 (26.4%)
MUSCLE SPASMS	3/163 (1.8%)		2/126 (1.6%)		3/51 (5.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		7/163 (4.3%)
MUSCULOSKELETAL PAIN	3/163 (1.8%)		10/126 (7.9%)		2/51 (3.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		15/163 (9.2%)
MYALGIA	4/163 (2.5%)		17/126 (13.5%)		2/51 (3.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		23/163 (14.1%)
PAIN IN EXTREMITY	11/163 (6.7%)		9/126 (7.1%)		2/51 (3.9%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		21/163 (12.9%)
Nervous system disorders
HEADACHE	8/163 (4.9%)		5/126 (4%)		1/51 (2%)		2/26 (7.7%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		16/163 (9.8%)
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	3/163 (1.8%)		2/126 (1.6%)		1/51 (2%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		1/6 (16.7%)		6/163 (3.7%)
Skin and subcutaneous tissue disorders
RASH	7/163 (4.3%)		1/126 (0.8%)		4/51 (7.8%)		0/26 (0%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		12/163 (7.4%)
Vascular disorders
HYPERTENSION	14/163 (8.6%)		7/126 (5.6%)		7/51 (13.7%)		1/26 (3.8%)		0/2 (0%)		0/1 (0%)		0/6 (0%)		22/163 (13.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. 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 pooled data (i.e.,data from all sites) in clinical trial.