Trial Outcomes & Findings for Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma (NCT NCT00765245)

Last Updated: 2016-04-11

Results Overview

Disease-free survival is the time from on-treatment to first relapse or death (whichever comes first). Those who are alive and without relapse are censored at the last date known alive.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

From on-treatment date to disease recurrence, up to 1 year

Results posted on

2016-04-11

Participant Flow

This study began enrolling patients October 2008 and continued until November 2013 when its study accrual goal was met. Patients were recruited from two academic medical institutions, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center and the University of North Carolina Medical Center, Chapel Hill.

Fifty-one patients signed consent to participate in this trial. Seven patients did not meet eligibility criteria, thus they did not receive treatment therapy and continue on study.

Participant milestones

Participant milestones
Measure	Arm I: Lenalidomide Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Overall Study STARTED	22	22
Overall Study COMPLETED	9	20
Overall Study NOT COMPLETED	13	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I: Lenalidomide Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Overall Study disease progression	3	2
Overall Study Withdrawal by Subject	3	0
Overall Study Adverse Event	5	0
Overall Study Physician Decision	1	0
Overall Study Death	1	0

Baseline Characteristics

Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I: Lenalidomide n=22 Participants Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV n=22 Participants Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Age, Continuous	60 years n=5 Participants	59.0 years n=7 Participants	59 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: From on-treatment date to disease recurrence, up to 1 year

Disease-free survival is the time from on-treatment to first relapse or death (whichever comes first). Those who are alive and without relapse are censored at the last date known alive.

Outcome measures

Outcome measures
Measure	Arm I: Lenalidomide n=22 Participants Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV n=22 Participants Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Disease-free Survival at 1 Year	0.818 years Interval 0.58 to 0.94	0.90 years Interval 0.58 to 0.94

SECONDARY outcome

Timeframe: From on-treatment date to disease recurrence, up to 2 years

Disease-free survival is the estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method where death is an event, with censoring for non-expired patients at last known date alive.

Outcome measures

Outcome measures
Measure	Arm I: Lenalidomide n=22 Participants Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV n=22 Participants Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Disease-free Survival at 2 Years	0.818 years Interval 0.585 to 0.928	0.757 years Interval 0.506 to 0.893

SECONDARY outcome

Timeframe: 30 days after completing treatment, for up to 13 months

Population: Total number of patients reported with any toxicity

Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening; grade 5, death. Toxicities present at baseline and continuing without change in grade are excluded when considering worst-grade toxicity.

Outcome measures

Outcome measures
Measure	Arm I: Lenalidomide n=19 Participants Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV n=21 Participants Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Number of Patients With Each Worst-Grade Toxicity Number of patients with WGT=1	2 participants	0 participants
Number of Patients With Each Worst-Grade Toxicity Number of patients with WGT=2	6 participants	8 participants
Number of Patients With Each Worst-Grade Toxicity Number of patients with WGT=3	6 participants	8 participants
Number of Patients With Each Worst-Grade Toxicity Number of patients with WGT=4	5 participants	5 participants
Number of Patients With Each Worst-Grade Toxicity Number of patients with WGT=5	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to two years

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: up to two years

Outcome measures

Outcome data not reported

Adverse Events

Arm I: Lenalidomide

Serious events: 8 serious events

Other events: 22 other events

Deaths: 0 deaths

Arm II: Lenalidomide and Rituximab IV

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Nishitha Reddy

Vanderbilt-Ingram Cancer Center

Phone: 800-811-8480

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm I: Lenalidomide n=22 participants at risk Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV n=22 participants at risk Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Nervous system disorders Pain - headache	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
General disorders Fatigue	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Nervous system disorders Cognitive disturbance	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Nervous system disorders Speech impairment	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Diarrhea	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Nervous system disorders Syncope (fainting)	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Renal and urinary disorders Obstruction - ureter	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Diverticulitis	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Pain - Abdomen NOS	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Investigations Neutrophils/granulocytes	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
General disorders Fever (in the absence of neutropenia)	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders vomiting	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Enteritis	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Investigations Infection	4.5% 1/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
General disorders Death NOS	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Secondary Malignancy	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Obstruction - small bowel	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).

Measure	Arm I: Lenalidomide n=22 participants at risk Lenalidomide: Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm II: Lenalidomide and Rituximab IV n=22 participants at risk Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity. Lenalidomide: Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles Rituximab: Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.
Metabolism and nutrition disorders hypoalbuminemia	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders alkaline phosphatase	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Respiratory, thoracic and mediastinal disorders allergic rhinitis	36.4% 8/22 • Number of events 8 • 30 days after completing treatment (up to 13 months).	31.8% 7/22 • Number of events 10 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders ALT, SGPT	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders anorexia	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders arthritis	13.6% 3/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders AST, SGOT	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Nervous system disorders ataxia - incooridnation	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Ear and labyrinth disorders auditory - other	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Injury, poisoning and procedural complications bruising	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders hypercalcemia	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders hypocalcemia	9.1% 2/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders hypercholesteremia	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Psychiatric disorders confusion	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders constipation	31.8% 7/22 • Number of events 10 • 30 days after completing treatment (up to 13 months).	31.8% 7/22 • Number of events 8 • 30 days after completing treatment (up to 13 months).
Respiratory, thoracic and mediastinal disorders cough	27.3% 6/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	50.0% 11/22 • Number of events 12 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders creatinine	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders dehydration	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders peridontal disease	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Skin and subcutaneous tissue disorders dermatology - other	18.2% 4/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders diarrhea	40.9% 9/22 • Number of events 11 • 30 days after completing treatment (up to 13 months).	50.0% 11/22 • Number of events 13 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders Distension	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Nervous system disorders dizziness	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders xerostomia (dry mouth)	13.6% 3/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
Skin and subcutaneous tissue disorders dry skin	18.2% 4/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).	31.8% 7/22 • Number of events 8 • 30 days after completing treatment (up to 13 months).
Respiratory, thoracic and mediastinal disorders dyspnea	13.6% 3/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
General disorders edema	22.7% 5/22 • Number of events 7 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 8 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders gait/walking disturbance	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
General disorders fatigue	63.6% 14/22 • Number of events 15 • 30 days after completing treatment (up to 13 months).	59.1% 13/22 • Number of events 15 • 30 days after completing treatment (up to 13 months).
Injury, poisoning and procedural complications fracture	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders gastrointestinal - other	22.7% 5/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders hyperglycemia	18.2% 4/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders dyspepsia (heartburn)	13.6% 3/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Investigations hemoglobin increase	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders hemorrhoids	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Vascular disorders hypertension	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Renal and urinary disorders incontinence	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Infections and infestations infection	59.1% 13/22 • Number of events 14 • 30 days after completing treatment (up to 13 months).	68.2% 15/22 • Number of events 18 • 30 days after completing treatment (up to 13 months).
Psychiatric disorders Insomnia	27.3% 6/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	27.3% 6/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders joint function	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Nervous system disorders laryngeal nerve dysfunction	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Blood and lymphatic system disorders leukocytes	13.6% 3/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
Nervous system disorders memory impairment	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders metabolic other	9.1% 2/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).	13.6% 3/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).
Psychiatric disorders mood alteration	27.3% 6/22 • Number of events 7 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders musculoskeletal soft tissue	27.3% 6/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	18.2% 4/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders myositis	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Respiratory, thoracic and mediastinal disorders paranasal sinus reactions	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders nausea	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 7 • 30 days after completing treatment (up to 13 months).
Nervous system disorders neuropathy	36.4% 8/22 • Number of events 10 • 30 days after completing treatment (up to 13 months).	50.0% 11/22 • Number of events 16 • 30 days after completing treatment (up to 13 months).
Investigations neutrophil count increased	40.9% 9/22 • Number of events 13 • 30 days after completing treatment (up to 13 months).	50.0% 11/22 • Number of events 15 • 30 days after completing treatment (up to 13 months).
General disorders pain - abdomen	31.8% 7/22 • Number of events 8 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders pain - back	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders pain - chest wall	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders pain - extremity	18.2% 4/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Nervous system disorders pain - headache	18.2% 4/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).	36.4% 8/22 • Number of events 9 • 30 days after completing treatment (up to 13 months).
Musculoskeletal and connective tissue disorders pain - joint	27.3% 6/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
General disorders pain - other, NOS	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	18.2% 4/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).
Metabolism and nutrition disorders hyperkalemia	18.2% 4/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Skin and subcutaneous tissue disorders desquamation - rash	50.0% 11/22 • Number of events 13 • 30 days after completing treatment (up to 13 months).	27.3% 6/22 • Number of events 9 • 30 days after completing treatment (up to 13 months).
Skin and subcutaneous tissue disorders acne/acneiform	22.7% 5/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).	18.2% 4/22 • Number of events 5 • 30 days after completing treatment (up to 13 months).
Renal and urinary disorders renal - other	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
General disorders rigors	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Cardiac disorders Supraventricular and nodal arrhythmia	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders dysgeusia	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Endocrine disorders hyperthyroidism	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Endocrine disorders hypothyroidism	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	18.2% 4/22 • Number of events 4 • 30 days after completing treatment (up to 13 months).
Renal and urinary disorders urinary frequency	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	13.6% 3/22 • Number of events 3 • 30 days after completing treatment (up to 13 months).
Renal and urinary disorders urinary retention	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	0.00% 0/22 • 30 days after completing treatment (up to 13 months).
Skin and subcutaneous tissue disorders urticaria	0.00% 0/22 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Eye disorders blurred vision	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).
Respiratory, thoracic and mediastinal disorders dysarthria	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).	4.5% 1/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).
Gastrointestinal disorders vomiting	31.8% 7/22 • Number of events 8 • 30 days after completing treatment (up to 13 months).	22.7% 5/22 • Number of events 6 • 30 days after completing treatment (up to 13 months).
Injury, poisoning and procedural complications non-infectious wound complication	4.5% 1/22 • Number of events 1 • 30 days after completing treatment (up to 13 months).	9.1% 2/22 • Number of events 2 • 30 days after completing treatment (up to 13 months).