Safety and Efficacy of BKM120 in Relapsed and Refractory NHL

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01693614
• Collaborator: (none)
• Enrollment: 72
• Locations: 20
• Arms: 3
• Actual Duration (Months): 52.7
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL).

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma	Drug: Buparlisib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Phase II Study of BKM120 in Subjects With Relapsed and Refractory Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma and Follicular Lymphoma
• Actual Study Start Date: Feb 28, 2013
• Actual Primary Completion Date: Jul 21, 2017
• Actual Study Completion Date: Jul 21, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DLBCL Cohort Diffuse large B-cell lymphoma cohort	Drug: Buparlisib; 100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days; Other Names: BKM120
Experimental: MCL Cohort Mantle cell lymphoma cohort	Drug: Buparlisib; 100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days; Other Names: BKM120
Experimental: FL Cohort Follicular lymphoma cohort	Drug: Buparlisib; 100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days; Other Names: BKM120

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) [Baseline up to 6 months]

   Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR

Secondary Outcome Measures

1. Progression- Free Survival (PFS) Based on Investigator Assessment (FAS) [Baseline up to approximately 44 months]

   Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.

2. Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS) [Baseline up to approximately 18 months]

   Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause

3. Overall Survival (OS) - Percentage of Participants With OS Events (FAS) [Baseline up to approximately 44 months]

   Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit

4. Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) [Baseline up to approximately 18 months]

   Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals

5. Overall Survival - Median (FAS) [Baseline up approximately 44 months]

   Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patient had a histologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma, or diffuse large B cell lymphoma.

2. Patient had relapsed or refractory disease and received at least one prior therapy.

3. Patient with diffuse large B cell lymphoma had received or was ineligible for autologous or allogeneic stem cell transplant.

4. Patient had at least one measurable nodal lesion (≥2 cm) according to Cheson criteria (Cheson 2007). In case where the patient had no measurable nodal lesions ≥ 2 cm in the long axis at baseline, then the patient must have had at least one measurable extra-nodal lesion.

5. Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

6. Patient had adequate bone marrow and organ function.

Exclusion Criteria:

1. Patient had received previous treatment with PI3K inhibitors

2. Patient had evidence of graft versus host disease (GVHD).

3. Patient had active or history of central nervous system (CNS) disease.

4. Patient had a concurrent malignancy or had a malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer).

5. Patient had a score ≥ 12 on the PHQ-9 questionnaire.

6. Patient had a GAD-7 mood scale score ≥ 15.

7. Pregnant or nursing women

8. Patient who did not use highly effective contraception methods to avoid becoming pregnant or conceiving offspring.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	University of Nebraska Medical Center Univ Nebraska	Omaha	Nebraska	United States	68198
3	Memorial Sloan Kettering Dept of Onc.	New York	New York	United States	10017
4	Medical University of South Carolina -Hollings Cancer Center Medical Univ of South Carolina	Charleston	South Carolina	United States	29425
5	University of Texas MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)	Houston	Texas	United States	77030
6	Novartis Investigative Site	Brugge		Belgium	8000
7	Novartis Investigative Site	Yvoir		Belgium	5530
8	Novartis Investigative Site	Marseille		France	13273
9	Novartis Investigative Site	Pierre-Benite Cedex		France	69495
10	Novartis Investigative Site	Rennes		France	35019
11	Novartis Investigative Site	Frankfurt		Germany	60590
12	Novartis Investigative Site	Wurzburg		Germany	97080
13	Novartis Investigative Site	Milano	MI	Italy	20133
14	Novartis Investigative Site	Milano	MI	Italy	20141
15	Novartis Investigative Site	Gyeonggi-do	Korea	Korea, Republic of	10408
16	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
17	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
18	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
19	Novartis Investigative Site	Izmir		Turkey	35040
20	Novartis Investigative Site	Samsun		Turkey	55139

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 9, 2016
• Statistical Analysis Plan - Jun 16, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01693614
• Other Study ID Numbers: CBKM120Z2402; 2012-002208-41
• First Posted: Sep 26, 2012
• Last Update Posted: Sep 28, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, PI3K inhibitor, Non-Hodgkin lymphoma, NHL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

Participant Flow

Pre-assignment Detail	Primary reason for not completing is presented

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort
Period Title: Overall Study
STARTED	26	22	24
COMPLETED	0	0	0
NOT COMPLETED	26	22	24

Baseline Characteristics

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort	Total
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort	Total of all reporting groups
Overall Participants	26	22	24	72
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (14.57)	67.9 (8.56)	61.4 (13.11)	62.9 (12.80)
Sex: Female, Male (Count of Participants)
Female	8 30.8%	4 18.2%	11 45.8%	23 31.9%
Male	18 69.2%	18 81.8%	13 54.2%	49 68.1%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	19 73.1%	17 77.3%	21 87.5%	57 79.2%
Black	0 0%	0 0%	1 4.2%	1 1.4%
Asian	3 11.5%	2 9.1%	2 8.3%	7 9.7%
Other	4 15.4%	3 13.6%	0 0%	7 9.7%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)
Description	Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR
Time Frame	Baseline up to 6 months

Outcome Measure Data

Analysis Population Description

different numbers represents satisfying particular criteria

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort
Measure Participants	26	22	24
ORR	11.5 44.2%	22.7 103.2%	25.0 104.2%
DCR	30.8 118.5%	81.8 371.8%	87.5 364.6%

2. Secondary Outcome

Title	Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)
Description	Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.
Time Frame	Baseline up to approximately 44 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort
Measure Participants	26	22	24
Median (95% Confidence Interval) [months]	1.8	11.3	9.1

3. Secondary Outcome

Title	Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)
Description	Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause
Time Frame	Baseline up to approximately 18 months

Outcome Measure Data

Analysis Population Description

Number analyzed represents participants satisfying criteria for duration of response

Arm/Group Title	DLBCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Follicular lymphoma cohort
Measure Participants	3	6
Median (95% Confidence Interval) [months]	2.2	11.0

4. Secondary Outcome

Title	Overall Survival (OS) - Percentage of Participants With OS Events (FAS)
Description	Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit
Time Frame	Baseline up to approximately 44 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort
Measure Participants	26	22	24
OS events	50.0 192.3%	22.7 103.2%	8.3 34.6%
Number censored	50.0 192.3%	77.3 351.4%	91.7 382.1%

5. Secondary Outcome

Title	Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)
Description	Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
Time Frame	Baseline up to approximately 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort
Measure Participants	26	22	24
2 month	83.6 321.5%	100.0 454.5%	100.0 416.7%
4 month	66.9 257.3%	90.2 410%	100.0 416.7%
6 month	43.8 168.5%	90.2 410%	95.2 396.7%
12 month	43.8 168.5%	77.8 353.6%	95.2 396.7%
18 month	43.8 168.5%	70.1 318.6%	95.2 396.7%

6. Secondary Outcome

Title	Overall Survival - Median (FAS)
Description	Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
Time Frame	Baseline up approximately 44 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DLBCL Cohort	MCL Cohort	FL Cohort
Arm/Group Description	Diffuse large B-cell lymphoma cohort	Mantle cell lymphoma cohort	Follicular lymphoma cohort
Measure Participants	26	22	24
Median (95% Confidence Interval) [months]	5.2	NA	NA

Adverse Events

Time Frame	Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 18 months
Arm/Group Title	DLBCL Cohort		MCL Cohort		FL Cohort
Arm/Group Description	DLBCL		MCL		FL
All Cause Mortality
	DLBCL Cohort		MCL Cohort		FL Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/26 (26.9%)		1/22 (4.5%)		0/24 (0%)
Serious Adverse Events
	DLBCL Cohort		MCL Cohort		FL Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/26 (46.2%)		12/22 (54.5%)		7/24 (29.2%)
Blood and lymphatic system disorders
Febrile neutropenia	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Thrombocytopenia	1/26 (3.8%)		1/22 (4.5%)		0/24 (0%)
Cardiac disorders
Cardio-respiratory arrest	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Gastrointestinal disorders
Anal fissure	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Dysphagia	1/26 (3.8%)		0/22 (0%)		1/24 (4.2%)
Gastrointestinal haemorrhage	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Nausea	2/26 (7.7%)		0/22 (0%)		0/24 (0%)
Proctalgia	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Rectal haemorrhage	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Vomiting	2/26 (7.7%)		0/22 (0%)		0/24 (0%)
General disorders
Gait disturbance	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
General physical health deterioration	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Malaise	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Performance status decreased	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Pyrexia	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Infections and infestations
Lung infection	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Meningitis	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Pneumonia	1/26 (3.8%)		2/22 (9.1%)		0/24 (0%)
Pneumonia streptococcal	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Septic shock	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Urinary tract infection	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Investigations
Blood glucose increased	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Failure to thrive	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Hyperglycaemia	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Hyponatraemia	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Tendonitis	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Transitional cell carcinoma	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Nervous system disorders
Cerebellar infarction	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Cerebral infarction	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Essential tremor	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Presyncope	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Psychiatric disorders
Confusional state	1/26 (3.8%)		2/22 (9.1%)		0/24 (0%)
Psychiatric decompensation	0/26 (0%)		1/22 (4.5%)		0/24 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Lung infiltration	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Pleural effusion	0/26 (0%)		1/22 (4.5%)		2/24 (8.3%)
Respiratory failure	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Upper respiratory tract congestion	1/26 (3.8%)		0/22 (0%)		0/24 (0%)
Skin and subcutaneous tissue disorders
Toxic skin eruption	0/26 (0%)		0/22 (0%)		1/24 (4.2%)
Other (Not Including Serious) Adverse Events
	DLBCL Cohort		MCL Cohort		FL Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/26 (96.2%)		22/22 (100%)		23/24 (95.8%)
Blood and lymphatic system disorders
Anaemia	1/26 (3.8%)		3/22 (13.6%)		2/24 (8.3%)
Leukopenia	1/26 (3.8%)		2/22 (9.1%)		0/24 (0%)
Neutropenia	2/26 (7.7%)		1/22 (4.5%)		1/24 (4.2%)
Thrombocytopenia	1/26 (3.8%)		1/22 (4.5%)		2/24 (8.3%)
Ear and labyrinth disorders
Vertigo	0/26 (0%)		3/22 (13.6%)		2/24 (8.3%)
Eye disorders
Cataract	0/26 (0%)		2/22 (9.1%)		0/24 (0%)
Dry eye	0/26 (0%)		0/22 (0%)		2/24 (8.3%)
Vision blurred	0/26 (0%)		1/22 (4.5%)		2/24 (8.3%)
Gastrointestinal disorders
Abdominal pain	4/26 (15.4%)		3/22 (13.6%)		1/24 (4.2%)
Constipation	3/26 (11.5%)		5/22 (22.7%)		3/24 (12.5%)
Diarrhoea	5/26 (19.2%)		6/22 (27.3%)		9/24 (37.5%)
Dyspepsia	2/26 (7.7%)		2/22 (9.1%)		4/24 (16.7%)
Gastrooesophageal reflux disease	0/26 (0%)		1/22 (4.5%)		2/24 (8.3%)
Nausea	8/26 (30.8%)		6/22 (27.3%)		10/24 (41.7%)
Vomiting	3/26 (11.5%)		0/22 (0%)		3/24 (12.5%)
General disorders
Asthenia	3/26 (11.5%)		5/22 (22.7%)		4/24 (16.7%)
Face oedema	0/26 (0%)		0/22 (0%)		2/24 (8.3%)
Fatigue	6/26 (23.1%)		8/22 (36.4%)		13/24 (54.2%)
Oedema peripheral	0/26 (0%)		0/22 (0%)		3/24 (12.5%)
Pyrexia	3/26 (11.5%)		2/22 (9.1%)		1/24 (4.2%)
Hepatobiliary disorders
Hepatotoxicity	0/26 (0%)		2/22 (9.1%)		0/24 (0%)
Infections and infestations
Gastroenteritis	1/26 (3.8%)		2/22 (9.1%)		0/24 (0%)
Herpes zoster	0/26 (0%)		2/22 (9.1%)		0/24 (0%)
Pneumonia	0/26 (0%)		2/22 (9.1%)		0/24 (0%)
Urinary tract infection	2/26 (7.7%)		1/22 (4.5%)		3/24 (12.5%)
Investigations
Blood lactate dehydrogenase increased	2/26 (7.7%)		0/22 (0%)		1/24 (4.2%)
Weight decreased	3/26 (11.5%)		8/22 (36.4%)		4/24 (16.7%)
Metabolism and nutrition disorders
Decreased appetite	2/26 (7.7%)		7/22 (31.8%)		7/24 (29.2%)
Diabetes mellitus	0/26 (0%)		0/22 (0%)		2/24 (8.3%)
Hyperglycaemia	10/26 (38.5%)		10/22 (45.5%)		6/24 (25%)
Hypokalaemia	3/26 (11.5%)		0/22 (0%)		1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Back pain	0/26 (0%)		2/22 (9.1%)		3/24 (12.5%)
Muscle spasms	0/26 (0%)		2/22 (9.1%)		3/24 (12.5%)
Myalgia	0/26 (0%)		0/22 (0%)		2/24 (8.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	2/26 (7.7%)		0/22 (0%)		0/24 (0%)
Nervous system disorders
Dizziness	1/26 (3.8%)		1/22 (4.5%)		2/24 (8.3%)
Dysgeusia	0/26 (0%)		0/22 (0%)		2/24 (8.3%)
Headache	0/26 (0%)		1/22 (4.5%)		5/24 (20.8%)
Memory impairment	0/26 (0%)		2/22 (9.1%)		1/24 (4.2%)
Neuropathy peripheral	0/26 (0%)		2/22 (9.1%)		1/24 (4.2%)
Tremor	1/26 (3.8%)		4/22 (18.2%)		2/24 (8.3%)
Psychiatric disorders
Agitation	1/26 (3.8%)		3/22 (13.6%)		1/24 (4.2%)
Anxiety	6/26 (23.1%)		7/22 (31.8%)		5/24 (20.8%)
Confusional state	0/26 (0%)		2/22 (9.1%)		1/24 (4.2%)
Depression	8/26 (30.8%)		7/22 (31.8%)		6/24 (25%)
Insomnia	2/26 (7.7%)		2/22 (9.1%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	2/26 (7.7%)		4/22 (18.2%)		4/24 (16.7%)
Dyspnoea	2/26 (7.7%)		2/22 (9.1%)		2/24 (8.3%)
Pleural effusion	0/26 (0%)		1/22 (4.5%)		2/24 (8.3%)
Skin and subcutaneous tissue disorders
Dry skin	0/26 (0%)		1/22 (4.5%)		3/24 (12.5%)
Pruritus	2/26 (7.7%)		3/22 (13.6%)		3/24 (12.5%)
Rash	2/26 (7.7%)		3/22 (13.6%)		4/24 (16.7%)
Vascular disorders
Hypertension	0/26 (0%)		4/22 (18.2%)		0/24 (0%)
Jugular vein thrombosis	0/26 (0%)		2/22 (9.1%)		0/24 (0%)

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.