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A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL (SEQUOIA)

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ClinicalTrials.gov Identifier: NCT03336333
Recruitment Status : Active, not recruiting
First Posted : November 8, 2017
Results First Posted : November 7, 2023
Last Update Posted : November 9, 2023
Sponsor:
Information provided by (Responsible Party):
BeiGene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions Drug: Zanubrutinib
Drug: Bendamustine
Drug: Rituximab
Drug: Venetoclax
Enrollment 590
Recruitment Details Available data are presented as of the primary analysis data cut-off date of 07MAY2021; as of the data cut-off date, all cohorts were ongoing.
Pre-assignment Details  
Arm/Group Title Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p) Cohort 2: Zanubrutinib With Del(17p)
Hide Arm/Group Description Bendamustine + rituximab in participants with chronic lymphocytic leukemia (CLL) without deletion 17p [del(17p)]; bendamustine 90 milligrams (mg)/m^2/day administered intravenously (IV) on the first 2 days of each cycle for 6 cycles; rituximab 375 mg/m^2 for Cycle 1 and 500 mg/m^2 for Cycles 2 to 6 (each cycle is 28 days) Zanubrutinib in participants with CLL without del(17p); 160 mg administered twice a day orally until unacceptable toxicity or disease progression Zanubrutinib in participants with CLL with del(17p); 160 mg administered twice a day orally until unacceptable toxicity or disease progression
Period Title: Overall Study
Started 238 241 111
Treated 227 240 111
Completed 0 0 0
Not Completed 238 241 111
Reason Not Completed
Remained on study at time of data cut-off             202             219             102
Death             14             16             8
Withdrawal by Subject             16             5             1
Physician Decision             5             1             0
Lost to Follow-up             1             0             0
Arm/Group Title Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p) Cohort 2: Zanubrutinib With Del(17p) Total
Hide Arm/Group Description Bendamustine + Rituximab in participants with CLL without del(17p); bendamustine 90 milligrams (mg)/m^2/day administered intravenously (IV) on the first 2 days of each cycle for 6 cycles; rituximab 375 mg/m^2 for Cycle 1 and 500 mg/m^2 for Cycles 2 to 6 (each cycle is 28 days) Zanubrutinib in participants with CLL without del(17p); 160 mg administered twice a day orally until unacceptable toxicity or disease progression Zanubrutinib in participants with CLL with del(17p); 160 mg administered twice a day orally until unacceptable toxicity or disease progression Total of all reporting groups
Overall Number of Baseline Participants 238 241 111 590
Hide Baseline Analysis Population Description
Intent-to-treat analysis set included all enrolled participants who were assigned to a treatment group (as of cut-off date of 07MAY2021)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 241 participants 111 participants 590 participants
<=18 years 0 0 0 0
Between 18 and 65 years 46 45 16 107
>=65 years 192 196 95 483
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 241 participants 111 participants 590 participants
Female 94 87 32 213
Male 144 154 79 377
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 241 participants 111 participants 590 participants
Hispanic or Latino 4 5 1 10
Not Hispanic or Latino 211 218 99 528
Unknown or Not Reported 23 18 11 52
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 241 participants 111 participants 590 participants
American Indian or Alaska Native 0 0 0 0
Asian 9 4 1 14
Native Hawaiian or Other Pacific Islander 0 1 0 1
Black or African American 1 4 0 5
White 206 221 105 532
More than one race 0 0 0 0
Unknown or Not Reported 22 11 5 38
1.Primary Outcome
Title Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR)
Hide Description PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the ICR per 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with small lymphocytic lymphoma (SLL).
Time Frame Up to approximately 3 years and 7 months (as of cut-off date of 07MAY2021)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set included all enrolled participants who were assigned to a treatment group
Arm/Group Title Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p)
Hide Arm/Group Description:
Bendamustine + Rituximab in participants with CLL without del(17p); bendamustine 90 milligrams (mg)/m^2/day administered intravenously (IV) on the first 2 days of each cycle for 6 cycles; rituximab 375 mg/m^2 for Cycle 1 and 500 mg/m^2 for Cycles 2 to 6 (each cycle is 28 days)
Zanubrutinib in participants with CLL without del(17p); 160 mg administered twice a day until unacceptable toxicity or disease progression
Overall Number of Participants Analyzed 238 241
Median (95% Confidence Interval)
Unit of Measure: Months
33.7 [1] 
(28.1 to NA)
NA [1] 
(NA to NA)
[1]
Not estimable due to low number of PFS events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: Bendamustine + Rituximab Without Del(17p), Cohort 1: Zanubrutinib Without Del(17p)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments One-sided
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.28 to 0.63
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Cohort 1: Overall Response Rate (ORR) Between Treatment Groups as Determined by ICR
Hide Description ORR in Cohort 1 is defined as the percentage of participants who achieve a complete response, complete response with incomplete bone marrow recovery, partial response, or partial response with lymphocytosis, determined by the ICR.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Pooled Cohort 1/1a: Overall Response Rate (ORR) Between Treatment Groups
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Cohort 1: Overall Survival (OS) Between Treatment Groups as Determined by the ICR
Hide Description OS in Cohort 1 is defined as the time from randomization to the date of death due to any reason.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Cohort 1: Duration of Response (DOR) Between Treatment Groups as Determined by the ICR
Hide Description Duration of response in Cohort 1 determined using the iwCLL criteria with modification for treatment related lymphocytosis (in participants with CLL) and the Lugano Classification for non-Hodgkin lymphoma (NHL; in participants with SLL), is defined as the time from the date that criteria for response (ie, partial response with lymphocytosis [PR-L] or better) are first met to the date that disease progression is objectively documented or death, whichever occurs first.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Pooled Cohort 1/1a: Duration of Response (DOR) Between Treatment Groups
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Cohort 1: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)
Hide Description PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the investigator per iwCLL guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with SLL.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Pooled Cohort 1/1a: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Cohort 1: Patient-reported Outcomes as Assessed by the (European Quality Of Life 5D 5L) EQ-5D-5L Questionnaire
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Cohort 1: Patient-reported Outcomes as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Questionnaire.
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Cohort 2: Overall Response Rate (ORR)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Cohort 2: Progression-free Survival (PFS)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Cohort 2: Duration of Response (DOR)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Cohort 3: Overall Response Rate (ORR)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Cohort 3: Progression-free Survival (PFS)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Cohort 3: Duration of Response (DOR)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Cohort 3: Rate of Undetectable Minimal Residual Disease (MRD4)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
18.Secondary Outcome
Title Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame Up to 5 years
Outcome Measure Data Not Reported
19.Secondary Outcome
Title Apparent Rate of Clearance of Zanubrutinib From Plasma (CL/F)CL/F
Hide Description [Not Specified]
Time Frame Predose up to 12 hours postdose
Outcome Measure Data Not Reported
20.Secondary Outcome
Title Cohort 1 Zanubrutinib Only Arms: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12)
Hide Description [Not Specified]
Time Frame Predose up to 12 hours postdose
Outcome Measure Data Not Reported
21.Secondary Outcome
Title Cohort 3: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12) of Zanubrutinib
Hide Description [Not Specified]
Time Frame Predose up to 12 hours postdose
Outcome Measure Data Not Reported
22.Secondary Outcome
Title Cohort 3: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12) of Zanubrutinib
Hide Description [Not Specified]
Time Frame Predose up to 12 hours postdose
Outcome Measure Data Not Reported
Time Frame All-cause mortality and adverse events (AEs): Up to approximately 3 years and 7 months (as of data cut-off date of 07MAY2021)
Adverse Event Reporting Description All-cause mortality is reported for all randomized participants. Serious and other AEs include participants who received at least one dose of study drug.
 
Arm/Group Title Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p) Cohort 2: Zanubrutinib With Del(17p)
Hide Arm/Group Description Bendamustine + Rituximab in participants with CLL without del(17p); bendamustine 90 milligrams (mg)/m^2/day administered intravenously (IV) on the first 2 days of each cycle for 6 cycles; rituximab 375 mg/m^2 for Cycle 1 and 500 mg/m^2 for Cycles 2 to 6 (each cycle is 28 days) Zanubrutinib in participants with CLL without del(17p); 160 mg administered twice a day orally until unacceptable toxicity or disease progression Zanubrutinib in participants with CLL with del(17p); 160 mg administered twice a day orally until unacceptable toxicity or disease progression
All-Cause Mortality
Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p) Cohort 2: Zanubrutinib With Del(17p)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/238 (5.88%)      16/241 (6.64%)      8/111 (7.21%)    
Hide Serious Adverse Events
Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p) Cohort 2: Zanubrutinib With Del(17p)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   113/227 (49.78%)      88/240 (36.67%)      45/111 (40.54%)    
Blood and lymphatic system disorders       
Anaemia † 1  5/227 (2.20%)  15 2/240 (0.83%)  6 1/111 (0.90%)  2
Febrile neutropenia † 1  11/227 (4.85%)  11 1/240 (0.42%)  1 1/111 (0.90%)  1
Immune thrombocytopenia † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Neutropenia † 1  4/227 (1.76%)  4 2/240 (0.83%)  2 0/111 (0.00%)  0
Pancytopenia † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Thrombocytopenia † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Cardiac disorders       
Acute coronary syndrome † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 0/111 (0.00%)  0
Acute myocardial infarction † 1  1/227 (0.44%)  1 2/240 (0.83%)  2 0/111 (0.00%)  0
Angina pectoris † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Angina unstable † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Atrial fibrillation † 1  1/227 (0.44%)  1 4/240 (1.67%)  4 3/111 (2.70%)  3
Bradycardia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Cardiac arrest † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Cardiac failure † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 1/111 (0.90%)  1
Cardiogenic shock † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Cardiovascular insufficiency † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Coronary artery disease † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Myocardial infarction † 1  2/227 (0.88%)  2 2/240 (0.83%)  2 0/111 (0.00%)  0
Myocardial ischaemia † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Palpitations † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Pulseless electrical activity † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Stress cardiomyopathy † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Ventricular tachycardia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Ear and labyrinth disorders       
Vertigo † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 0/111 (0.00%)  0
Eye disorders       
Retinal detachment † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain † 1  2/227 (0.88%)  2 1/240 (0.42%)  1 1/111 (0.90%)  1
Diarrhoea † 1  5/227 (2.20%)  5 0/240 (0.00%)  0 0/111 (0.00%)  0
Enterocolitis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Ileus † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Inguinal hernia † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Intestinal obstruction † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Intra-abdominal haematoma † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Nausea † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Obstructive pancreatitis † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Oesophageal food impaction † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Pancreatitis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Rectal haemorrhage † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 0/111 (0.00%)  0
Retroperitoneal haematoma † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Small intestinal obstruction † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Upper gastrointestinal haemorrhage † 1  1/227 (0.44%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Vomiting † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
General disorders       
Fatigue † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Hyperpyrexia † 1  1/227 (0.44%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Implant site erosion † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Malaise † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pyrexia † 1  17/227 (7.49%)  19 2/240 (0.83%)  2 2/111 (1.80%)  3
Systemic inflammatory response syndrome † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Hepatobiliary disorders       
Biliary colic † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Cholangitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Cholecystitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Cholecystitis acute † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Gallbladder rupture † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Hepatotoxicity † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Regenerative siderotic hepatic nodule † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Immune system disorders       
Drug hypersensitivity † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Infections and infestations       
Abdominal sepsis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Abscess of salivary gland † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Appendicitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 2/111 (1.80%)  3
Bacteraemia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Bronchitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Bronchopulmonary aspergillosis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
COVID-19 † 1  1/227 (0.44%)  1 8/240 (3.33%)  8 1/111 (0.90%)  1
COVID-19 pneumonia † 1  0/227 (0.00%)  0 7/240 (2.92%)  7 1/111 (0.90%)  1
Cellulitis † 1  0/227 (0.00%)  0 3/240 (1.25%)  3 0/111 (0.00%)  0
Cholecystitis infective † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Chronic sinusitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Clostridium difficile colitis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Clostridium difficile infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Disseminated varicella zoster virus infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Diverticulitis † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Endocarditis † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Erysipelas † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Escherichia urinary tract infection † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Gastroenteritis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Groin abscess † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
H3N2 influenza † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Hepatitis B reactivation † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Infected skin ulcer † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Infection † 1  4/227 (1.76%)  4 1/240 (0.42%)  1 0/111 (0.00%)  0
Infective exacerbation of bronchiectasis † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 0/111 (0.00%)  0
Influenza † 1  1/227 (0.44%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Intervertebral discitis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Lower respiratory tract infection † 1  2/227 (0.88%)  2 1/240 (0.42%)  1 1/111 (0.90%)  1
Neuroborreliosis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Neutropenic sepsis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Otitis externa † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Otitis media acute † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Parainfluenzae virus infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pneumonia † 1  7/227 (3.08%)  8 4/240 (1.67%)  5 6/111 (5.41%)  6
Pneumonia chlamydial † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pneumonia pneumococcal † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Pneumonia viral † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Postoperative wound infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pseudomonal bacteraemia † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pseudomonal sepsis † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 1/111 (0.90%)  1
Respiratory syncytial virus infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Respiratory tract infection † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Respiratory tract infection fungal † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Sepsis † 1  6/227 (2.64%)  7 2/240 (0.83%)  2 0/111 (0.00%)  0
Sialoadenitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Skin infection † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Soft tissue infection † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 0/111 (0.00%)  0
Systemic candida † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Tick-borne fever † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Upper respiratory tract infection † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 0/111 (0.00%)  0
Urinary tract infection † 1  5/227 (2.20%)  6 1/240 (0.42%)  2 2/111 (1.80%)  2
Urosepsis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 2/111 (1.80%)  2
Viral infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Viral pericarditis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Wound infection † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Injury, poisoning and procedural complications       
Bone contusion † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Chest injury † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Contusion † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Fall † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 3/111 (2.70%)  4
Femoral neck fracture † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Femur fracture † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Infusion related reaction † 1  7/227 (3.08%)  8 0/240 (0.00%)  0 0/111 (0.00%)  0
Limb injury † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Lumbar vertebral fracture † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Patella fracture † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Pelvic fracture † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Post procedural haemorrhage † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Radius fracture † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Scrotal haematoma † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Spinal compression fracture † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Spinal fracture † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 1/111 (0.90%)  1
Stomal hernia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Thoracic vertebral fracture † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Tibia fracture † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Investigations       
Alanine aminotransferase increased † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Aspartate aminotransferase increased † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Blood alkaline phosphatase increased † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Blood creatinine increased † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Blood pressure increased † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Gamma-glutamyltransferase increased † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Metabolism and nutrition disorders       
Adult failure to thrive † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Dehydration † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Gout † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Hypercalcaemia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Hypervolaemia † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Hyponatraemia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Tumour lysis syndrome † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Back pain † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 1/111 (0.90%)  1
Chondrocalcinosis pyrophosphate † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Intervertebral disc disorder † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Musculoskeletal chest pain † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Myalgia † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Pain in extremity † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Rotator cuff syndrome † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Spinal pain † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Spinal stenosis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma gastric † 1  1/227 (0.44%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Basal cell carcinoma † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 0/111 (0.00%)  0
Benign neoplasm of bladder † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Bladder cancer † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 1/111 (0.90%)  1
Bladder transitional cell carcinoma † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Bowen's disease † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Breast cancer † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Colon adenoma † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
External ear neoplasm malignant † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Intraductal papillary mucinous neoplasm † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Large intestine benign neoplasm † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Lung adenocarcinoma † 1  0/227 (0.00%)  0 3/240 (1.25%)  3 1/111 (0.90%)  1
Lung neoplasm malignant † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Lung squamous cell carcinoma recurrent † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 0/111 (0.00%)  0
Malignant melanoma † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 2/111 (1.80%)  2
Malignant pleural effusion † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Metastatic squamous cell carcinoma † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 0/111 (0.00%)  0
Non-small cell lung cancer † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Prostate cancer † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Rectal adenocarcinoma † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Renal cancer † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 0/111 (0.00%)  0
Skin squamous cell carcinoma metastatic † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Squamous cell carcinoma of lung † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Squamous cell carcinoma of skin † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 1/111 (0.90%)  1
Transitional cell carcinoma urethra † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Tumour flare † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Tumour pain † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Nervous system disorders       
Carpal tunnel syndrome † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Cerebral infarction † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Cerebrovascular accident † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 1/111 (0.90%)  1
Dizziness † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Encephalopathy † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Facial paralysis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Haemorrhagic transformation stroke † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Headache † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 2/111 (1.80%)  2
Hydrocephalus † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Hypertensive encephalopathy † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Radial nerve palsy † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Transient ischaemic attack † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Psychiatric disorders       
Confusional state † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Bladder stenosis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Calculus bladder † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Haematuria † 1  1/227 (0.44%)  1 2/240 (0.83%)  2 1/111 (0.90%)  1
Hydronephrosis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Nephrolithiasis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 2/111 (1.80%)  2
Renal colic † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Renal failure † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Ureteral polyp † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Urethral stenosis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Urinary retention † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 1/111 (0.90%)  1
Urinary tract obstruction † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 0/111 (0.00%)  0
Reproductive system and breast disorders       
Benign prostatic hyperplasia † 1  0/227 (0.00%)  0 2/240 (0.83%)  2 2/111 (1.80%)  2
Perineal pain † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Prostatitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Chronic obstructive pulmonary disease † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 0/111 (0.00%)  0
Epistaxis † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Hypoxia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Lung disorder † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Nasal congestion † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Oropharyngeal pain † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pleural effusion † 1  0/227 (0.00%)  0 1/240 (0.42%)  2 2/111 (1.80%)  2
Pneumonia aspiration † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Pneumonitis † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pneumothorax † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Productive cough † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Pulmonary embolism † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Respiratory failure † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Skin and subcutaneous tissue disorders       
Purpura † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Rash † 1  3/227 (1.32%)  3 0/240 (0.00%)  0 0/111 (0.00%)  0
Rash maculo-papular † 1  2/227 (0.88%)  2 0/240 (0.00%)  0 0/111 (0.00%)  0
Skin ulcer † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Toxic skin eruption † 1  1/227 (0.44%)  1 0/240 (0.00%)  0 0/111 (0.00%)  0
Vascular disorders       
Aortic dissection † 1  0/227 (0.00%)  0 0/240 (0.00%)  0 1/111 (0.90%)  1
Aortic intramural haematoma † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Arteriosclerosis † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
Hypertension † 1  1/227 (0.44%)  1 1/240 (0.42%)  1 0/111 (0.00%)  0
Hypotension † 1  1/227 (0.44%)  2 0/240 (0.00%)  0 1/111 (0.90%)  1
Peripheral ischaemia † 1  0/227 (0.00%)  0 1/240 (0.42%)  1 0/111 (0.00%)  0
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Cohort 1: Bendamustine + Rituximab Without Del(17p) Cohort 1: Zanubrutinib Without Del(17p) Cohort 2: Zanubrutinib With Del(17p)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   214/227 (94.27%)      208/240 (86.67%)      104/111 (93.69%)    
Blood and lymphatic system disorders       
Anaemia † 1  41/227 (18.06%)  65 11/240 (4.58%)  12 5/111 (4.50%)  7
Leukopenia † 1  7/227 (3.08%)  12 1/240 (0.42%)  1 0/111 (0.00%)  0
Neutropenia † 1  101/227 (44.49%)  233 30/240 (12.50%)  62 13/111 (11.71%)  28
Thrombocytopenia † 1  30/227 (13.22%)  62 8/240 (3.33%)  15 4/111 (3.60%)  4
Cardiac disorders       
Palpitations † 1  3/227 (1.32%)  3 10/240 (4.17%)  10 3/111 (2.70%)  3
Ear and labyrinth disorders       
Vertigo † 1  2/227 (0.88%)  4 9/240 (3.75%)  12 2/111 (1.80%)  2
Gastrointestinal disorders       
Abdominal pain † 1  12/227 (5.29%)  13 11/240 (4.58%)  16 9/111 (8.11%)  10
Constipation † 1  43/227 (18.94%)  49 24/240 (10.00%)  26 17/111 (15.32%)  18
Diarrhoea † 1  26/227 (11.45%)  37 33/240 (13.75%)  42 20/111 (18.02%)  24
Dry mouth † 1  9/227 (3.96%)  10 3/240 (1.25%)  3 0/111 (0.00%)  0
Dyspepsia † 1  8/227 (3.52%)  8 10/240 (4.17%)  12 10/111 (9.01%)  12
Haemorrhoids † 1  7/227 (3.08%)  7 2/240 (0.83%)  2 2/111 (1.80%)  2
Nausea † 1  74/227 (32.60%)  107 24/240 (10.00%)  30 18/111 (16.22%)  26
Stomatitis † 1  8/227 (3.52%)  9 5/240 (2.08%)  5 1/111 (0.90%)  1
Vomiting † 1  31/227 (13.66%)  40 17/240 (7.08%)  23 8/111 (7.21%)  9
General disorders       
Asthenia † 1  18/227 (7.93%)  25 5/240 (2.08%)  6 4/111 (3.60%)  6
Chest pain † 1  2/227 (0.88%)  2 9/240 (3.75%)  9 2/111 (1.80%)  2
Chills † 1  19/227 (8.37%)  21 3/240 (1.25%)  3 5/111 (4.50%)  6
Fatigue † 1  36/227 (15.86%)  52 28/240 (11.67%)  37 10/111 (9.01%)  14
Oedema peripheral † 1  16/227 (7.05%)  17 18/240 (7.50%)  25 8/111 (7.21%)  9
Peripheral swelling † 1  6/227 (2.64%)  7 9/240 (3.75%)  11 4/111 (3.60%)  4
Pyrexia † 1  46/227 (20.26%)  69 15/240 (6.25%)  15 6/111 (5.41%)  7
Immune system disorders       
Drug hypersensitivity † 1  8/227 (3.52%)  9 1/240 (0.42%)  1 0/111 (0.00%)  0
Infections and infestations       
Bronchitis † 1  15/227 (6.61%)  17 6/240 (2.50%)  6 3/111 (2.70%)  3
COVID-19 † 1  7/227 (3.08%)  8 16/240 (6.67%)  16 3/111 (2.70%)  5
Cellulitis † 1  2/227 (0.88%)  2 12/240 (5.00%)  15 2/111 (1.80%)  2
Conjunctivitis † 1  6/227 (2.64%)  9 4/240 (1.67%)  4 4/111 (3.60%)  7
Herpes zoster † 1  9/227 (3.96%)  9 5/240 (2.08%)  5 1/111 (0.90%)  1
Lower respiratory tract infection † 1  4/227 (1.76%)  6 8/240 (3.33%)  11 6/111 (5.41%)  6
Nasopharyngitis † 1  12/227 (5.29%)  15 16/240 (6.67%)  16 11/111 (9.91%)  13
Oral herpes † 1  7/227 (3.08%)  8 3/240 (1.25%)  3 2/111 (1.80%)  2
Pharyngitis † 1  0/227 (0.00%)  0 1/240 (0.42%)  3 4/111 (3.60%)  5
Pneumonia † 1  13/227 (5.73%)  14 8/240 (3.33%)  9 8/111 (7.21%)  11
Respiratory tract infection † 1  8/227 (3.52%)  9 7/240 (2.92%)  15 5/111 (4.50%)  6
Sinusitis † 1  10/227 (4.41%)  11 12/240 (5.00%)  12 6/111 (5.41%)  7
Upper respiratory tract infection † 1  27/227 (11.89%)  32 41/240 (17.08%)  53 23/111 (20.72%)  29
Urinary tract infection † 1  16/227 (7.05%)  28 16/240 (6.67%)  29 9/111 (8.11%)  11
Injury, poisoning and procedural complications       
Contusion † 1  8/227 (3.52%)  8 46/240 (19.17%)  58 22/111 (19.82%)  31
Fall † 1  7/227 (3.08%)  12 9/240 (3.75%)  11 9/111 (8.11%)  9
Infusion related reaction † 1  39/227 (17.18%)  44 1/240 (0.42%)  1 0/111 (0.00%)  0
Skin laceration † 1  4/227 (1.76%)  5 4/240 (1.67%)  4 6/111 (5.41%)  7
Investigations       
Alanine aminotransferase increased † 1  10/227 (4.41%)  18 3/240 (1.25%)  7 0/111 (0.00%)  0
Aspartate aminotransferase increased † 1  9/227 (3.96%)  12 3/240 (1.25%)  6 0/111 (0.00%)  0
Blood creatinine increased † 1  2/227 (0.88%)  2 2/240 (0.83%)  2 4/111 (3.60%)  4
Neutrophil count decreased † 1  28/227 (12.33%)  69 6/240 (2.50%)  14 7/111 (6.31%)  17
Platelet count decreased † 1  11/227 (4.85%)  20 2/240 (0.83%)  2 4/111 (3.60%)  13
Weight decreased † 1  7/227 (3.08%)  7 2/240 (0.83%)  2 2/111 (1.80%)  2
Metabolism and nutrition disorders       
Decreased appetite † 1  18/227 (7.93%)  18 7/240 (2.92%)  10 1/111 (0.90%)  1
Dehydration † 1  8/227 (3.52%)  13 1/240 (0.42%)  1 1/111 (0.90%)  1
Gout † 1  4/227 (1.76%)  6 4/240 (1.67%)  5 6/111 (5.41%)  7
Hyperuricaemia † 1  9/227 (3.96%)  13 6/240 (2.50%)  7 2/111 (1.80%)  2
Hypokalaemia † 1  12/227 (5.29%)  26 4/240 (1.67%)  5 3/111 (2.70%)  3
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  19/227 (8.37%)  24 32/240 (13.33%)  40 22/111 (19.82%)  25
Back pain † 1  15/227 (6.61%)  20 21/240 (8.75%)  26 16/111 (14.41%)  19
Bone pain † 1  9/227 (3.96%)  10 1/240 (0.42%)  2 1/111 (0.90%)  1
Muscle spasms † 1  4/227 (1.76%)  5 8/240 (3.33%)  10 7/111 (6.31%)  8
Musculoskeletal chest pain † 1  1/227 (0.44%)  1 7/240 (2.92%)  8 4/111 (3.60%)  5
Myalgia † 1  3/227 (1.32%)  3 9/240 (3.75%)  11 6/111 (5.41%)  8
Neck pain † 1  1/227 (0.44%)  1 5/240 (2.08%)  5 7/111 (6.31%)  9
Pain in extremity † 1  12/227 (5.29%)  13 15/240 (6.25%)  23 10/111 (9.01%)  11
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma † 1  3/227 (1.32%)  4 9/240 (3.75%)  12 12/111 (10.81%)  17
Nervous system disorders       
Dizziness † 1  10/227 (4.41%)  13 19/240 (7.92%)  21 8/111 (7.21%)  10
Headache † 1  17/227 (7.49%)  19 26/240 (10.83%)  31 11/111 (9.91%)  14
Peripheral sensory neuropathy † 1  4/227 (1.76%)  4 1/240 (0.42%)  1 4/111 (3.60%)  4
Sciatica † 1  4/227 (1.76%)  5 3/240 (1.25%)  4 4/111 (3.60%)  4
Psychiatric disorders       
Insomnia † 1  16/227 (7.05%)  17 10/240 (4.17%)  11 3/111 (2.70%)  3
Renal and urinary disorders       
Acute kidney injury † 1  8/227 (3.52%)  9 1/240 (0.42%)  1 2/111 (1.80%)  2
Haematuria † 1  5/227 (2.20%)  5 12/240 (5.00%)  16 10/111 (9.01%)  12
Pollakiuria † 1  3/227 (1.32%)  3 3/240 (1.25%)  3 4/111 (3.60%)  4
Respiratory, thoracic and mediastinal disorders       
Cough † 1  23/227 (10.13%)  27 27/240 (11.25%)  33 14/111 (12.61%)  18
Dyspnoea † 1  9/227 (3.96%)  12 8/240 (3.33%)  8 11/111 (9.91%)  11
Epistaxis † 1  1/227 (0.44%)  1 12/240 (5.00%)  22 7/111 (6.31%)  8
Oropharyngeal pain † 1  6/227 (2.64%)  6 10/240 (4.17%)  11 3/111 (2.70%)  3
Productive cough † 1  1/227 (0.44%)  1 9/240 (3.75%)  10 6/111 (5.41%)  6
Skin and subcutaneous tissue disorders       
Dry skin † 1  7/227 (3.08%)  7 6/240 (2.50%)  8 3/111 (2.70%)  3
Ecchymosis † 1  1/227 (0.44%)  1 7/240 (2.92%)  8 6/111 (5.41%)  8
Erythema † 1  8/227 (3.52%)  11 7/240 (2.92%)  8 3/111 (2.70%)  3
Petechiae † 1  0/227 (0.00%)  0 18/240 (7.50%)  22 5/111 (4.50%)  6
Pruritus † 1  16/227 (7.05%)  22 20/240 (8.33%)  24 10/111 (9.01%)  11
Rash † 1  42/227 (18.50%)  59 26/240 (10.83%)  31 16/111 (14.41%)  19
Rash maculo-papular † 1  10/227 (4.41%)  12 8/240 (3.33%)  10 4/111 (3.60%)  4
Skin lesion † 1  2/227 (0.88%)  2 9/240 (3.75%)  12 5/111 (4.50%)  5
Vascular disorders       
Haematoma † 1  1/227 (0.44%)  1 13/240 (5.42%)  18 6/111 (5.41%)  8
Hypertension † 1  19/227 (8.37%)  21 28/240 (11.67%)  36 10/111 (9.01%)  13
Hypotension † 1  21/227 (9.25%)  25 6/240 (2.50%)  6 4/111 (3.60%)  5
1
Term from vocabulary, MedDRA 24.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: BeiGene
Phone: 1-877-828-5568
EMail: clinicaltrials@beigene.com
Publications of Results:
Mu S, Tang Z, Novotny W, Tawashi M, Li TK, Ou Y, Sahasranaman S. Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects. Cancer Chemother Pharmacol. 2020 Feb;85(2):391-399. doi: 10.1007/s00280-019-04015-w. Epub 2019 Dec 26.
Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, Simpson D, Shadman M, Ganly PS, Laurenti L, Opat S, Tani M, Ciepluch H, Verner E, Simkovic M, Osterborg A, Trneny M, Tedeschi A, Paik JC, Kuwahara SB, Feng S, Ramakrishnan V, Cohen A, Huang J, Hillmen P, Brown JR. Zanubrutinib monotherapy for patients with treatment naive chronic lymphocytic leukemia and 17p deletion. Haematologica. 2021 Sep 1;106(9):2354-2363. doi: 10.3324/haematol.2020.259432.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03336333    
Other Study ID Numbers: BGB-3111-304
2017-001551-31 ( EudraCT Number )
CTR20190416 ( Registry Identifier: Center for drug evaluation, NMPA )
First Submitted: November 1, 2017
First Posted: November 8, 2017
Results First Submitted: October 16, 2023
Results First Posted: November 7, 2023
Last Update Posted: November 9, 2023