Safety And Efficacy Of Lenalidomide In Patients With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma (NHL)

• Sponsor: Celgene Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00179660
• Collaborator: Prologue Research International (Industry)
• Enrollment: 50
• Locations: 8
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To determine the activity of lenalidomide in relapsed or refractory aggressive NHL.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkins Lymphoma	Drug: Lenalidomide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Single-Arm, Open-Label Study To Evaluate The Safety And Efficacy Of Single-Agent Lenalidomide (Revlimid®, CC-5013) In Subjects With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.	Drug: Lenalidomide; Capsules for oral administration.; Other Names: CC-5013 Revlimid®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Response [From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.]

   Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.

Secondary Outcome Measures

1. Percentage of Participants With Tumor Control [From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.]

   Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders. Appearance of any new lesion during or at the end of therapy.

2. Duration of Response [From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.]

   The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.

3. Duration of Tumor Control [From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.]

   The duration of tumor control was calculated as the time from the first response assessment demonstrating at least stable disease to the first documentation of progressive disease or death due to NHL. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.

4. Progression-free Survival [From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.]

   Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.

5. Number of Participants With Adverse Events (AEs) [From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 15.2 months.]

   The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.

2. Age greater than or equal to 18 years at the time of signing the informed consent form

3. Able to adhere to the study visit schedule and other protocol requirements

4. Biopsy-proven non-Hodgkin's lymphoma

5. Aggressive lymphoma, the following histologies are acceptable: Follicular center lymphoma, grade 3, Diffuse large cell, Mantle cell, Transformed

6. Relapsed or refractory to previous therapy for lymphoma. Patients must have received at least one prior treatment regimen such as radiation, immunotherapy, chemotherapy, or radioimmunotherapy, and be ineligible or unwilling to undergo an autologous stem cell transplant. There is no limit on the number of prior therapies.

7. Patients must have measurable disease on cross sectional imaging that is at least 2 cm in the longest diameter.

8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

9. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug.

Exclusion Criteria:

1. Any of the following laboratory abnormalities:

2. Absolute neutrophil count (ANC) <1,500 cells/mm^{3 (1.5 x 10}9/L)

3. Platelet count <100,000/mm^{3 (100 x 10}9/L)

4. Serum creatinine >2.5 mg/dL (221 mmol/L)

5. Serum aspartate transaminase (AST) or alanine transaminase (ALT) >5.0 x upper limit of normal (ULN)

6. Serum total bilirubin >2.0 mg/dL (34 mmol/L)

7. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

8. All patients with central nervous system (CNS) disease with the exception of those patients whose CNS disease has been treated with chemotherapy, radiotherapy or surgery and remains asymptomatic, with no active CNS disease, as shown by lumbar puncture, computed tomography (CT) scan or magnetic resonance imaging (MRI), for at least 6 months.

9. Prior history of malignancies other than non-Hodgkin's lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for > or equal to 1 year

10. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

11. Known positive for human immunodeficiency virus (HIV)

12. Pregnant or lactating females

13. Prior > or equal to grade 3 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction/hypersensitivity to thalidomide

14. Prior > or equal to grade 3 NCI CTCAE rash or any desquamating (blistering) rash while taking thalidomide

15. Prior use of lenalidomide

16. Use of any standard or experimental anti-cancer drug therapy within 28 days of day 1 of study drug therapy

17. Known active Hepatitis C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259
2	Pacific Coast Hematology/Oncology Medical Group, Onc.	Fountain Valley	California	United States	92708
3	UC David Cancer Center	Sacramento	California	United States	95817
4	Sylvester Cancer CenterUniversity Of Miami	Miami	Florida	United States	33136
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	University of Nebraska	Omaha	Nebraska	United States	68198-6805
7	New York Medical Center, MBCCOP	Bronx	New York	United States	10466
8	Gunderson Clinic, Ltd	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• Celgene Corporation
• Prologue Research International

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene Corporation
• ClinicalTrials.gov Identifier: NCT00179660
• Other Study ID Numbers: CC-5013-NHL-002
• First Posted: Sep 16, 2005
• Last Update Posted: Jan 21, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Celgene Corporation: celgene; cc-5013; CC5013; NHL; Non-Hodgkins Lymphoma; Revlimid
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Period Title: Overall Study
STARTED	50
Received Study Drug	49
Completed 12 Cycles of Treatment	12
COMPLETED	0
NOT COMPLETED	50

Baseline Characteristics

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Participants	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (11.53)
Sex: Female, Male (Count of Participants)
Female	24 49%
Male	25 51%
Race/Ethnicity, Customized (participants) [Number]
White	36 73.5%
Black	2 4.1%
Hispanic	10 20.4%
Asian/Pacific Islander	1 2%
Region of Enrollment (participants) [Number]
United States	49 100%
Eastern Cooperative Oncology Group (ECOG) performance status (participants) [Number]
0	20 40.8%
1	23 46.9%
2	5 10.2%
Missing	1 2%
Non-Hodgkin's Lymphoma (NHL) Stage (participants) [Number]
Stage I	1 2%
Stage II	7 14.3%
Stage III	9 18.4%
Stage IV	32 65.3%
NHL histology (participants) [Number]
Follicular lymphoma grade 3	5 10.2%
Diffuse large B-cell lymphoma	26 53.1%
Mantle cell lymphoma	15 30.6%
Transformed	3 6.1%
NHL Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.0 (4.91)
International Prognostic Index (IPI) (participants) [Number]
Low (0 to 1)	8 16.3%
Low/Intermediate (2)	22 44.9%
High/Intermediate (3)	13 26.5%
High (4 to 5)	6 12.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Response
Description	Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD) Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.
Time Frame	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population, which included all enrolled patients who received at least 1 dose of study drug. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders.

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	34.7 70.8%

2. Secondary Outcome

Title	Percentage of Participants With Tumor Control
Description	Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders. Appearance of any new lesion during or at the end of therapy.
Time Frame	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders.

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	49
Number (95% Confidence Interval) [percentage of participants]	59.2 120.8%

3. Secondary Outcome

Title	Duration of Response
Description	The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.
Time Frame	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Outcome Measure Data

Analysis Population Description

Intent to treat population with a response = CR, CRu or PR.

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	17
Median (95% Confidence Interval) [months]	10.2

4. Secondary Outcome

Title	Duration of Tumor Control
Description	The duration of tumor control was calculated as the time from the first response assessment demonstrating at least stable disease to the first documentation of progressive disease or death due to NHL. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.
Time Frame	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Outcome Measure Data

Analysis Population Description

Intent to treat population with tumor control (CR, CRu, PR or SD).

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	29
Median (95% Confidence Interval) [months]	6.0

5. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.
Time Frame	From enrollment through study completion. Median duration on study was 3.7 months, with a maximum of 32.5 months.

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	49
Median (95% Confidence Interval) [months]	3.6

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.
Time Frame	From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 15.2 months.

Outcome Measure Data

Analysis Population Description

Safety Population, which includes all participants who received at least one dose of study drug.

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Measure Participants	49
Any adverse event	49 100%
Adverse event related to study drug	42 85.7%
Grade 3-5 adverse event	36 73.5%
Grade 3-5 adverse event related to study drug	27 55.1%
Serious adverse event	21 42.9%
Serious adverse event related to study drug	6 12.2%
AE leading to discontinuation of study drug	9 18.4%
Related AE leading to study drug discontinuation	4 8.2%
AE leading to dose reduction or interruption	28 57.1%

Adverse Events

Time Frame	From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 15.2 months
Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
All Cause Mortality
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	21/49 (42.9%)
Blood and lymphatic system disorders
Febrile neutropenia	2/49 (4.1%)
Thrombocytopenia	2/49 (4.1%)
Anemia NOS	1/49 (2%)
Coombs positive hemolytic anemia	1/49 (2%)
Cardiac disorders
Acute myocardial infarction	1/49 (2%)
Cardiac failure congestive	1/49 (2%)
Gastrointestinal disorders
Abdominal pain NOS	1/49 (2%)
Abdominal pain upper	1/49 (2%)
Dysphagia	1/49 (2%)
General disorders
Pyrexia	3/49 (6.1%)
Chest pain	1/49 (2%)
Malaise	1/49 (2%)
Immune system disorders
Autoimmune disorder NOS	1/49 (2%)
Infections and infestations
Pneumonia NOS	3/49 (6.1%)
Bronchopneumonia NOS	1/49 (2%)
Cellulitis	1/49 (2%)
Osteomyelitis NOS	1/49 (2%)
Sepsis NOS	1/49 (2%)
Staphylococcal bacteremia	1/49 (2%)
Investigations
Alanine aminotransferase increased	1/49 (2%)
Aspartate aminotransferase increased	1/49 (2%)
Blood bilirubin increased	1/49 (2%)
Musculoskeletal and connective tissue disorders
Back pain	1/49 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma NOS	4/49 (8.2%)
Breast cancer NOS	1/49 (2%)
Central nervous system lymphoma	1/49 (2%)
Small cell lung cancer stage unspecified	1/49 (2%)
Nervous system disorders
Cauda equina syndrome	1/49 (2%)
Convulsions NOS	1/49 (2%)
Spinal hematoma	1/49 (2%)
Psychiatric disorders
Mental status changes	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea NOS	2/49 (4.1%)
Pneumonitis NOS	1/49 (2%)
Pulmonary embolism	1/49 (2%)
Skin and subcutaneous tissue disorders
Sweating increased	1/49 (2%)
Vascular disorders
Jugular vein thrombosis	1/49 (2%)
Other (Not Including Serious) Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	48/49 (98%)
Blood and lymphatic system disorders
Neutropenia	19/49 (38.8%)
Thrombocytopenia	18/49 (36.7%)
Anaemia NOS	15/49 (30.6%)
Leukopenia NOS	6/49 (12.2%)
Lymphopenia	4/49 (8.2%)
Gastrointestinal disorders
Constipation	15/49 (30.6%)
Diarrhoea NOS	12/49 (24.5%)
Nausea	10/49 (20.4%)
Abdominal Pain NOS	4/49 (8.2%)
Vomiting NOS	4/49 (8.2%)
General disorders
Fatigue	19/49 (38.8%)
Pyrexia	8/49 (16.3%)
Oedema Peripheral	6/49 (12.2%)
Pain NOS	3/49 (6.1%)
Infections and infestations
Infection NOS	4/49 (8.2%)
Upper Respiratory Tract Infection NOS	4/49 (8.2%)
Urinary Tract Infection NOS	3/49 (6.1%)
Investigations
Platelet Count Decreased	11/49 (22.4%)
Neutrophil Count Decreased	9/49 (18.4%)
White Blood Cell Count Decreased	9/49 (18.4%)
Haemoglobin Decreased	8/49 (16.3%)
Alanine Aminotransferase Increased	4/49 (8.2%)
Aspartate Aminotransferase Increased	3/49 (6.1%)
Blood Alkaline Phosphatase NOS Increased	3/49 (6.1%)
Blood Creatinine Increased	3/49 (6.1%)
Metabolism and nutrition disorders
Anorexia	8/49 (16.3%)
Hyperglycaemia NOS	4/49 (8.2%)
Hyperkalaemia	4/49 (8.2%)
Hypermagnesaemia	3/49 (6.1%)
Hypocalcaemia	3/49 (6.1%)
Hypokalaemia	3/49 (6.1%)
Hypomagnesaemia	3/49 (6.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/49 (16.3%)
Muscle Cramp	7/49 (14.3%)
Back Pain	3/49 (6.1%)
Myalgia	3/49 (6.1%)
Nervous system disorders
Peripheral Sensory Neuropathy	7/49 (14.3%)
Dizziness	5/49 (10.2%)
Peripheral Neuropathy NOS	5/49 (10.2%)
Dysgeusia	3/49 (6.1%)
Headache	3/49 (6.1%)
Neuropathy NOS	3/49 (6.1%)
Psychiatric disorders
Insomnia	7/49 (14.3%)
Depression	3/49 (6.1%)
Respiratory, thoracic and mediastinal disorders
Cough	10/49 (20.4%)
Dyspnoea NOS	6/49 (12.2%)
Pharyngitis	5/49 (10.2%)
Nasopharyngitis	3/49 (6.1%)
Rhinorrhoea	3/49 (6.1%)
Skin and subcutaneous tissue disorders
Rash NOS	13/49 (26.5%)
Night Sweats	5/49 (10.2%)
Pruritus	3/49 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.