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A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Participants With Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT02329847
Recruitment Status : Completed
First Posted : January 1, 2015
Results First Posted : June 15, 2023
Last Update Posted : June 15, 2023
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hematologic Neoplasms
Interventions Drug: Ibrutinib
Drug: Nivolumab
Enrollment 144
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Period Title: Overall Study
Started 7 7 36 35 39 20
Treated (Safety Analysis Set) 7 7 35 35 37 20
Completed 0 0 1 0 0 0
Not Completed 7 7 35 35 39 20
Reason Not Completed
Death             4             4             22             12             20             13
Lost to Follow-up             0             0             2             3             0             1
Physician Decision             0             0             0             0             1             0
Withdrawal by Subject             2             1             5             7             8             3
Other             1             2             6             13             10             3
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg Total
Hide Arm/Group Description Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Total of all reporting groups
Overall Number of Baseline Participants 7 7 35 35 37 20 141
Hide Baseline Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 7 participants 35 participants 35 participants 37 participants 20 participants 141 participants
61  (18.08) 65.9  (13.96) 64.3  (9.57) 61.3  (11.94) 59.2  (15.99) 64.9  (11.19) 62.2  (12.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 35 participants 35 participants 37 participants 20 participants 141 participants
Female
4
  57.1%
4
  57.1%
9
  25.7%
15
  42.9%
10
  27.0%
12
  60.0%
54
  38.3%
Male
3
  42.9%
3
  42.9%
26
  74.3%
20
  57.1%
27
  73.0%
8
  40.0%
87
  61.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 35 participants 35 participants 37 participants 20 participants 141 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
   2.9%
3
   8.6%
0
   0.0%
0
   0.0%
4
   2.8%
Not Hispanic or Latino
7
 100.0%
7
 100.0%
34
  97.1%
31
  88.6%
35
  94.6%
20
 100.0%
134
  95.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.9%
2
   5.4%
0
   0.0%
3
   2.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 7 participants 7 participants 35 participants 35 participants 37 participants 20 participants 141 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
  28.6%
0
   0.0%
1
   2.9%
2
   5.4%
0
   0.0%
5
   3.5%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
7
 100.0%
5
  71.4%
35
 100.0%
33
  94.3%
34
  91.9%
20
 100.0%
134
  95.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.7%
0
   0.0%
1
   0.7%
Other
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.9%
0
   0.0%
0
   0.0%
1
   0.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 7 participants 7 participants 35 participants 35 participants 37 participants 20 participants 141 participants
AUSTRALIA
0
   0.0%
0
   0.0%
2
   5.7%
1
   2.9%
8
  21.6%
1
   5.0%
12
   8.5%
ISRAEL
6
  85.7%
1
  14.3%
4
  11.4%
8
  22.9%
6
  16.2%
0
   0.0%
25
  17.7%
POLAND
0
   0.0%
0
   0.0%
18
  51.4%
6
  17.1%
6
  16.2%
10
  50.0%
40
  28.4%
SPAIN
1
  14.3%
3
  42.9%
5
  14.3%
6
  17.1%
2
   5.4%
4
  20.0%
21
  14.9%
TURKEY
0
   0.0%
0
   0.0%
6
  17.1%
6
  17.1%
8
  21.6%
1
   5.0%
21
  14.9%
UNITED STATES
0
   0.0%
3
  42.9%
0
   0.0%
8
  22.9%
7
  18.9%
4
  20.0%
22
  15.6%
1.Primary Outcome
Title Overall Response Rate (ORR) as Assessed International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008: Disease Cohort
Hide Description ORR is percentage of participants achieving a complete response (CR), CR with incomplete marrow recovery (CRi), nodular partial response (nPR) or PR. IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/L, platelets >100*10^9/L, Hgb >11 g/dL and absolute lymphocyte count <4000/mcL; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR- >=50% drop in lymphocyte count from baseline or <=4.0*10^9/L with following: >=50% decrease in sum products of up to 6 lymph nodes, no new enlarged lymph nodes, When abnormal, >=50% decrease in enlargement of spleen from baseline or normalization and a response in 1 of following: Neutrophils >1.5*10^9/L, Platelets>100000/mcL and Hgb>11 g/dL or >=50% improvement over baseline in all. This outcome measure was planned to be analyzed for specified arm only.
Time Frame Up to 6 years 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab). The ORR evaluation criteria were disease specific and hence the analysis was done as per disease cohorts for this outcome measure as pre-planned.
Arm/Group Title Ibrutinib and Nivolumab: Chronic Lymphocytic Leukemia (CLL)
Hide Arm/Group Description:
Participants with CLL in Cohort A1 and B1, received ibrutinib 420 milligrams (mg) capsules orally, daily starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilograms (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: Percentage of Participants
63.3
2.Primary Outcome
Title Overall Response Rate (ORR) as Assessed Non-Hodgkin Lymphoma (NHL), Cheson 2014: Disease Cohort
Hide Description ORR defined as percentage of participants achieving a CR, CRi, nPR or PR. As per Non-Hodgkin Lymphoma, Cheson 2014, CR is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is >= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive disease (PD) >= 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. This outcome measure was planned to be analyzed for specified arms only.
Time Frame Up to 6 years 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab). The ORR evaluation criteria were disease specific and hence the analysis was done as per disease cohorts for this outcome measure as pre-planned.
Arm/Group Title Ibrutinib and Nivolumab: Small Lymphocytic Lymphoma (SLL) Ibrutinib and Nivolumab: Follicular Lymphoma (FL) Ibrutinib and Nivolumab: Diffuse Large B-cell Lymphoma (DLBCL) Ibrutinib and Nivolumab: Richter
Hide Arm/Group Description:
Participants with SLL in Cohort B1, received ibrutinib 420 mg capsules orally, daily starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilograms (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL in Cohorts A1, A2, and B2, and who had histologically confirmed initial diagnosis of FL, received ibrutinib either 420 or 560 mg capsules orally, daily starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilograms (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL in Cohorts A1, A2, and B3, and who had histologically confirmed disease with at least 1 measurable disease site, received ibrutinib either 420 or 560 mg capsules orally, daily starting on Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants who had histologically confirmed Richter syndrome in Cohort B4 with at least 1 site of measurable disease, received ibrutinib 560 mg capsules orally, daily starting on Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 6 40 45 20
Measure Type: Number
Unit of Measure: Percentage of Participants
50.0 32.5 37.8 65.0
3.Primary Outcome
Title Percentage of Participants With Treatment-emergent Adverse Event (TEAEs): Study Cohort
Hide Description An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs for the treatment phase included events with an onset date/time on or after the start of study intervention through end of study were considered as treatment-emergent.
Time Frame Up to 6 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of study drugs (either ibrutinib or nivolumab).
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description:
Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 7 7 35 35 37 20
Measure Type: Number
Unit of Measure: Percentage of Participants
100 100 100 100 97.3 95.0
4.Secondary Outcome
Title Duration of Response (DoR): Study Cohort
Hide Description DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and date of first documented evidence of progressive disease or death or date of censoring. iWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (>=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.
Time Frame Up to 6 years 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and achieved either PR or better (including PRL only for CLL participants).
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description:
Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 2 1 26 12 15 13
Median (95% Confidence Interval)
Unit of Measure: Months
11.5
(2.4 to 20.7)
NA [1] 
(NA to NA)
19.2
(9.4 to 19.4)
10.2
(5.1 to 17.8)
NA [2] 
(4.6 to NA)
6.9 [3] 
(1.3 to NA)
[1]
Here 'NA' indicates that median and 95% CI could not be estimated due to less number of participants with events.
[2]
Here 'NA' indicates that median and upper limit of 95% CI could not be estimated due to less number of participants with events.
[3]
Here 'NA' indicates that upper limit of 95% CI could not be estimated due to less number of participants with events.
5.Secondary Outcome
Title Duration of Stable Disease or Better: Study Cohort
Hide Description Duration of stable disease or better was defined as duration from the start of the treatment until the criteria for progression were met. IWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.
Time Frame Up to 6 years and 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and met criteria for progressive disease. Here 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description:
Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 1 1 5 7 1 0
Median (Full Range)
Unit of Measure: Months
24.8
(24.8 to 24.8)
20.8
(20.8 to 20.8)
17.38
(14.0 to 21.6)
14.55
(12.7 to 20.4)
14.1
(14.1 to 14.1)
6.Secondary Outcome
Title Progression-free Survival (PFS): Study Cohort
Hide Description PFS is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. Participants who were progression-free and alive or had unknown status were censored at the last tumor assessment. IWCLL 2008 criteria for progressive disease: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.
Time Frame Up to 6 years 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and met criteria for progressive disease.
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description:
Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 6 5 16 26 22 11
Median (95% Confidence Interval)
Unit of Measure: Months
2.0
(1.1 to 24.8)
9.1
(0.7 to 20.8)
21.6
(12.0 to 21.6)
7.6
(2.9 to 12.7)
3.2 [1] 
(2.1 to NA)
5.0 [1] 
(2.4 to NA)
[1]
Here 'NA' indicates that upper limit of 95% CI could not be estimated due to less number of participants with events.
7.Secondary Outcome
Title Overall Survival (OS): Study Cohort
Hide Description OS was defined as duration from the date of first dose of study drug to the date of the participant's death.
Time Frame Up to 6 years 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab) and were responders.
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description:
Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 4 3 11 9 16 8
Median (95% Confidence Interval)
Unit of Measure: Months
12.4
(2.0 to 28.8)
NA [1] 
(0.8 to NA)
NA [1] 
(21.6 to NA)
NA [2] 
(NA to NA)
19.0 [3] 
(7.7 to NA)
10.3 [3] 
(4.8 to NA)
[1]
Here 'NA' indicates that median and upper limit of 95% CI could not be estimated due to less number of participants with events.
[2]
Here 'NA' indicates that median and 95% CI could not be estimated due to less number of participants with events.
[3]
Here 'NA' indicates that upper limit of 95% CI could not be estimated due to less number of participants with events.
8.Secondary Outcome
Title Percentage of Participants With Lymphoma-related Symptoms: Study Cohort
Hide Description Percentage of participants with lymphoma-related symptoms were reported. These symptoms included B-symptoms, recurrent fever, night sweats, weight loss, other disease-related symptoms, itching, fatigue, physical discomfort and any other.
Time Frame Up to 6 years 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
The all-treated population included all participants who had received at least 1 dose of study drugs (either ibrutinib or nivolumab).
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description:
Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
Overall Number of Participants Analyzed 7 7 35 35 37 20
Measure Type: Number
Unit of Measure: Percentage of Participants
14.3 42.9 74.3 25.7 54.1 60.0
Time Frame Up to 6 years 11 months
Adverse Event Reporting Description All-cause mortality was assessed on all randomized participants. Serious adverse events and other adverse events were assessed on safety analysis set which included all participants who received at least 1 dose of study drugs (either ibrutinib or nivolumab).
 
Arm/Group Title Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Hide Arm/Group Description Participants with chronic lymphocytic leukemia (CLL)/ follicular cell lymphoma (FL)/diffuse large B-cell lymphoma (DLBCL), received ibrutinib 420 milligrams (mg) capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kilogram (kg) as an intravenous (IV) infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with FL/DLBCL, received ibrutinib 560 mg capsule orally once daily starting from Day 1 of Cycle 1 up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with CLL/small lymphocytic lymphoma (SLL) with deletion (del) 17p or 11q, received ibrutinib 420 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with FL, received ibrutinib 560 mg orally once daily, starting at 7 days prior to Day 1 of Cycle 1 as a run-in period and then daily thereafter up to 56 cycles (26 months). Participants also received nivolumab 3 mg/kg as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with DLBCL, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days. Participants with richter syndrome, received ibrutinib 560 mg orally once daily, starting from Day 1 of Cycle 1 up to 56 cycles (26 months), along with nivolumab 3 mg/kg administered as an IV infusion on Day 1 of each cycle up to 56 cycles. Each cycle was of 14 days.
All-Cause Mortality
Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/7 (57.14%)   4/7 (57.14%)   22/36 (61.11%)   12/35 (34.29%)   20/39 (51.28%)   13/20 (65.00%) 
Hide Serious Adverse Events
Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/7 (57.14%)   3/7 (42.86%)   23/35 (65.71%)   15/35 (42.86%)   23/37 (62.16%)   15/20 (75.00%) 
Blood and lymphatic system disorders             
Anaemia * 1  0/7 (0.00%)  1/7 (14.29%)  2/35 (5.71%)  0/35 (0.00%)  3/37 (8.11%)  0/20 (0.00%) 
Febrile Neutropenia * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Lymphadenopathy * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  2/20 (10.00%) 
Neutropenia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Pancytopenia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Splenomegaly * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Cardiac disorders             
Atrial Fibrillation * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Cardiac Failure * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Cardiotoxicity * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Myocardial Infarction * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Eye disorders             
Cataract * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders             
Abdominal Discomfort * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Abdominal Pain * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/37 (5.41%)  0/20 (0.00%) 
Colitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Diarrhoea * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Enterocolitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Gastric Haemorrhage * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Gastritis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Gastrointestinal Haemorrhage * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Gastrointestinal Inflammation * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Intestinal Obstruction * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Large Intestine Perforation * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Oesophageal Compression * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Pancreatitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Stomatitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
General disorders             
Asthenia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Chest Pain * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Chills * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Fatigue * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
General Physical Health Deterioration * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Mucosal Inflammation * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Multiple Organ Dysfunction Syndrome * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Oedema Peripheral * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Pyrexia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  2/37 (5.41%)  1/20 (5.00%) 
Unevaluable Event * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Hepatobiliary disorders             
Bile Duct Stone * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Biliary Obstruction * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Cholangitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Cholecystitis * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Portal Vein Thrombosis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Immune system disorders             
Hypersensitivity * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Infections and infestations             
Anal Abscess * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Arthritis Bacterial * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Bacteraemia * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Cellulitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Covid-19 * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Encephalitis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Enterococcal Bacteraemia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Erysipelas * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Gastroenteritis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Influenza * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Nasopharyngitis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Otitis Media * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Otitis Media Chronic * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Pneumocystis Jirovecii Pneumonia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Pneumonia * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  2/35 (5.71%)  1/37 (2.70%)  2/20 (10.00%) 
Pneumonia Bacterial * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Pneumonia Fungal * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Pneumonia Klebsiella * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Pneumonia Parainfluenzae Viral * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Respiratory Syncytial Virus Infection * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Respiratory Tract Infection Bacterial * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Rhinovirus Infection * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Sepsis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Septic Shock * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Upper Respiratory Tract Infection * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Urinary Tract Infection * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Urinary Tract Infection Bacterial * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Viral Upper Respiratory Tract Infection * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Wound Infection * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications             
Pancreatic Injury * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Investigations             
Alanine Aminotransferase Increased * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Immunoglobulins Decreased * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Transaminases Increased * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Metabolism and nutrition disorders             
Diabetes Mellitus Inadequate Control * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Hypoalbuminaemia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Hyponatraemia * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Back Pain * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Basal Cell Carcinoma * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Leukaemic Infiltration * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Malignant Neoplasm Progression * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Penile Squamous Cell Carcinoma * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Renal Neoplasm * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Nervous system disorders             
Migraine * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Transient Ischaemic Attack * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Renal and urinary disorders             
Acute Kidney Injury * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Haematuria * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Hydronephrosis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  2/37 (5.41%)  0/20 (0.00%) 
Renal Failure * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Urinary Retention * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Reproductive system and breast disorders             
Benign Prostatic Hyperplasia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Prostatomegaly * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Asphyxia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Chronic Obstructive Pulmonary Disease * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Dyspnoea * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/37 (5.41%)  2/20 (10.00%) 
Organising Pneumonia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Pleural Effusion * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Pneumonitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/37 (5.41%)  1/20 (5.00%) 
Pneumothorax * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Respiratory Arrest * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Respiratory Failure * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders             
Rash Maculo-Papular * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Vascular disorders             
Aortic Aneurysm * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA Version 24.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A1 (CLL/FL/DLBCL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort A2 (FL/DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B1 (CLL/SLL): Ibrutinib 420 mg + Nivolumab 3 mg/kg Cohort B2 (FL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B3 (DLBCL): Ibrutinib 560 mg + Nivolumab 3 mg/kg Cohort B4 (Richter Syndrome): Ibrutinib 560 mg + Nivolumab 3 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/7 (100.00%)   7/7 (100.00%)   35/35 (100.00%)   35/35 (100.00%)   35/37 (94.59%)   19/20 (95.00%) 
Blood and lymphatic system disorders             
Anaemia * 1  1/7 (14.29%)  2/7 (28.57%)  9/35 (25.71%)  5/35 (14.29%)  11/37 (29.73%)  8/20 (40.00%) 
Febrile Neutropenia * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Leukocytosis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Lymphocytosis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Lymphopenia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Neutropenia * 1  2/7 (28.57%)  0/7 (0.00%)  20/35 (57.14%)  7/35 (20.00%)  10/37 (27.03%)  8/20 (40.00%) 
Thrombocytopenia * 1  1/7 (14.29%)  0/7 (0.00%)  11/35 (31.43%)  5/35 (14.29%)  7/37 (18.92%)  3/20 (15.00%) 
Cardiac disorders             
Atrial Fibrillation * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  2/35 (5.71%)  2/37 (5.41%)  1/20 (5.00%) 
Atrioventricular Block First Degree * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Cardiac Failure * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Palpitations * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Endocrine disorders             
Euthyroid Sick Syndrome * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Hypothyroidism * 1  0/7 (0.00%)  1/7 (14.29%)  3/35 (8.57%)  1/35 (2.86%)  3/37 (8.11%)  0/20 (0.00%) 
Eye disorders             
Eye Haemorrhage * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  2/37 (5.41%)  0/20 (0.00%) 
Lacrimation Increased * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Miosis * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Gastrointestinal disorders             
Abdominal Distension * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Abdominal Pain * 1  0/7 (0.00%)  1/7 (14.29%)  3/35 (8.57%)  5/35 (14.29%)  5/37 (13.51%)  1/20 (5.00%) 
Abdominal Pain Lower * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Abdominal Pain Upper * 1  1/7 (14.29%)  0/7 (0.00%)  3/35 (8.57%)  2/35 (5.71%)  1/37 (2.70%)  1/20 (5.00%) 
Anal Ulcer * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Constipation * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  3/35 (8.57%)  5/37 (13.51%)  0/20 (0.00%) 
Diarrhoea * 1  5/7 (71.43%)  1/7 (14.29%)  13/35 (37.14%)  12/35 (34.29%)  12/37 (32.43%)  5/20 (25.00%) 
Dry Mouth * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Dyspepsia * 1  2/7 (28.57%)  1/7 (14.29%)  3/35 (8.57%)  3/35 (8.57%)  2/37 (5.41%)  0/20 (0.00%) 
Dysphagia * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Gastric Fistula * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Gastrooesophageal Reflux Disease * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  3/37 (8.11%)  1/20 (5.00%) 
Gingival Bleeding * 1  0/7 (0.00%)  2/7 (28.57%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Intra-Abdominal Haematoma * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Melaena * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Nausea * 1  1/7 (14.29%)  2/7 (28.57%)  3/35 (8.57%)  7/35 (20.00%)  9/37 (24.32%)  1/20 (5.00%) 
Stomatitis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  3/35 (8.57%)  3/37 (8.11%)  2/20 (10.00%) 
Toothache * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Vomiting * 1  1/7 (14.29%)  1/7 (14.29%)  2/35 (5.71%)  0/35 (0.00%)  6/37 (16.22%)  1/20 (5.00%) 
General disorders             
Asthenia * 1  1/7 (14.29%)  2/7 (28.57%)  3/35 (8.57%)  5/35 (14.29%)  1/37 (2.70%)  1/20 (5.00%) 
Chills * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  2/37 (5.41%)  1/20 (5.00%) 
Fatigue * 1  2/7 (28.57%)  3/7 (42.86%)  6/35 (17.14%)  14/35 (40.00%)  11/37 (29.73%)  1/20 (5.00%) 
Gait Disturbance * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
General Physical Health Deterioration * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Generalised Oedema * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Inflammation * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Influenza Like Illness * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Mucosal Inflammation * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Non-Cardiac Chest Pain * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  4/35 (11.43%)  0/37 (0.00%)  0/20 (0.00%) 
Oedema Peripheral * 1  2/7 (28.57%)  0/7 (0.00%)  7/35 (20.00%)  3/35 (8.57%)  3/37 (8.11%)  3/20 (15.00%) 
Pain * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Peripheral Swelling * 1  0/7 (0.00%)  1/7 (14.29%)  2/35 (5.71%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Pyrexia * 1  2/7 (28.57%)  2/7 (28.57%)  10/35 (28.57%)  5/35 (14.29%)  9/37 (24.32%)  6/20 (30.00%) 
Hepatobiliary disorders             
Hyperbilirubinaemia * 1  1/7 (14.29%)  1/7 (14.29%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Immune system disorders             
Drug Hypersensitivity * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Secondary Immunodeficiency * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  2/37 (5.41%)  1/20 (5.00%) 
Infections and infestations             
Bronchitis * 1  1/7 (14.29%)  0/7 (0.00%)  4/35 (11.43%)  2/35 (5.71%)  2/37 (5.41%)  1/20 (5.00%) 
Cellulitis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  3/35 (8.57%)  1/37 (2.70%)  1/20 (5.00%) 
Conjunctivitis * 1  0/7 (0.00%)  2/7 (28.57%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  2/20 (10.00%) 
Covid-19 * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Cytomegalovirus Infection Reactivation * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Folliculitis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Fungal Skin Infection * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Gallbladder Abscess * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Gastroenteritis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Herpes Simplex * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  1/37 (2.70%)  1/20 (5.00%) 
Herpes Zoster * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/37 (5.41%)  0/20 (0.00%) 
Influenza * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  3/37 (8.11%)  0/20 (0.00%) 
Klebsiella Infection * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Laryngitis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Lower Respiratory Tract Infection * 1  0/7 (0.00%)  0/7 (0.00%)  4/35 (11.43%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Lymphangitis * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Nasopharyngitis * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  4/35 (11.43%)  1/37 (2.70%)  0/20 (0.00%) 
Oral Candidiasis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Oral Herpes * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Otitis Media * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Paronychia * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  1/37 (2.70%)  2/20 (10.00%) 
Periodontitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Pharyngitis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Pneumonia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  3/35 (8.57%)  5/37 (13.51%)  0/20 (0.00%) 
Pneumonia Bacterial * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Pulpitis Dental * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Respiratory Tract Infection * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Rhinovirus Infection * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Sinusitis * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  4/35 (11.43%)  1/37 (2.70%)  0/20 (0.00%) 
Tonsillitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Upper Respiratory Tract Infection * 1  2/7 (28.57%)  1/7 (14.29%)  11/35 (31.43%)  10/35 (28.57%)  7/37 (18.92%)  7/20 (35.00%) 
Urinary Tract Infection * 1  1/7 (14.29%)  1/7 (14.29%)  3/35 (8.57%)  2/35 (5.71%)  3/37 (8.11%)  2/20 (10.00%) 
Viral Infection * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Viral Pharyngitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Viral Upper Respiratory Tract Infection * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Wound Infection * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Wound Infection Staphylococcal * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Injury, poisoning and procedural complications             
Contusion * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  3/37 (8.11%)  1/20 (5.00%) 
Fall * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Limb Injury * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Nasal Injury * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Traumatic Haematoma * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Investigations             
Alanine Aminotransferase Increased * 1  1/7 (14.29%)  1/7 (14.29%)  4/35 (11.43%)  4/35 (11.43%)  5/37 (13.51%)  4/20 (20.00%) 
Amylase Increased * 1  1/7 (14.29%)  1/7 (14.29%)  5/35 (14.29%)  1/35 (2.86%)  3/37 (8.11%)  1/20 (5.00%) 
Aspartate Aminotransferase Increased * 1  0/7 (0.00%)  2/7 (28.57%)  4/35 (11.43%)  3/35 (8.57%)  3/37 (8.11%)  4/20 (20.00%) 
Blood Alkaline Phosphatase * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  2/37 (5.41%)  0/20 (0.00%) 
Blood Alkaline Phosphatase Increased * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  1/35 (2.86%)  3/37 (8.11%)  1/20 (5.00%) 
Blood Bilirubin Increased * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  2/37 (5.41%)  2/20 (10.00%) 
Blood Creatine Phosphokinase Increased * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Blood Creatinine Increased * 1  1/7 (14.29%)  2/7 (28.57%)  3/35 (8.57%)  2/35 (5.71%)  5/37 (13.51%)  0/20 (0.00%) 
Blood Lactate Dehydrogenase Increased * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  1/37 (2.70%)  1/20 (5.00%) 
Blood Pressure Increased * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Blood Thyroid Stimulating Hormone Increased * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Blood Uric Acid Increased * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Gamma-Glutamyltransferase Increased * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Lipase Increased * 1  2/7 (28.57%)  2/7 (28.57%)  8/35 (22.86%)  2/35 (5.71%)  5/37 (13.51%)  3/20 (15.00%) 
Neutrophil Count Decreased * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Platelet Count Decreased * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  2/20 (10.00%) 
Serum Ferritin Decreased * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  1/37 (2.70%)  0/20 (0.00%) 
Weight Decreased * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  2/35 (5.71%)  1/37 (2.70%)  0/20 (0.00%) 
Metabolism and nutrition disorders             
Decreased Appetite * 1  1/7 (14.29%)  1/7 (14.29%)  3/35 (8.57%)  3/35 (8.57%)  4/37 (10.81%)  0/20 (0.00%) 
Dehydration * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  3/37 (8.11%)  0/20 (0.00%) 
Glucose Tolerance Impaired * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Hypercalcaemia * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  0/35 (0.00%)  3/37 (8.11%)  0/20 (0.00%) 
Hyperglycaemia * 1  0/7 (0.00%)  0/7 (0.00%)  4/35 (11.43%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Hyperkalaemia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Hypernatraemia * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Hyperuricaemia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Hypoalbuminaemia * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Hypocalcaemia * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Hypokalaemia * 1  2/7 (28.57%)  0/7 (0.00%)  8/35 (22.86%)  6/35 (17.14%)  7/37 (18.92%)  5/20 (25.00%) 
Hypomagnesaemia * 1  1/7 (14.29%)  0/7 (0.00%)  3/35 (8.57%)  5/35 (14.29%)  1/37 (2.70%)  0/20 (0.00%) 
Hyponatraemia * 1  2/7 (28.57%)  1/7 (14.29%)  1/35 (2.86%)  2/35 (5.71%)  2/37 (5.41%)  1/20 (5.00%) 
Hypoproteinaemia * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Iron Deficiency * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  1/37 (2.70%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  2/7 (28.57%)  0/7 (0.00%)  10/35 (28.57%)  5/35 (14.29%)  5/37 (13.51%)  1/20 (5.00%) 
Arthritis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  4/35 (11.43%)  1/37 (2.70%)  0/20 (0.00%) 
Back Pain * 1  2/7 (28.57%)  1/7 (14.29%)  4/35 (11.43%)  4/35 (11.43%)  5/37 (13.51%)  1/20 (5.00%) 
Bone Pain * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Groin Pain * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Joint Swelling * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Muscle Spasms * 1  0/7 (0.00%)  1/7 (14.29%)  3/35 (8.57%)  4/35 (11.43%)  9/37 (24.32%)  0/20 (0.00%) 
Muscular Weakness * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  1/35 (2.86%)  2/37 (5.41%)  0/20 (0.00%) 
Musculoskeletal Chest Pain * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Myalgia * 1  0/7 (0.00%)  0/7 (0.00%)  5/35 (14.29%)  3/35 (8.57%)  3/37 (8.11%)  0/20 (0.00%) 
Pain in Extremity * 1  1/7 (14.29%)  0/7 (0.00%)  4/35 (11.43%)  6/35 (17.14%)  3/37 (8.11%)  1/20 (5.00%) 
Tendonitis * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Basal Cell Carcinoma * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Skin Papilloma * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Tumour Haemorrhage * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Tumour Pain * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Nervous system disorders             
Dizziness * 1  0/7 (0.00%)  1/7 (14.29%)  1/35 (2.86%)  1/35 (2.86%)  3/37 (8.11%)  0/20 (0.00%) 
Dizziness Postural * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Headache * 1  1/7 (14.29%)  1/7 (14.29%)  3/35 (8.57%)  5/35 (14.29%)  5/37 (13.51%)  0/20 (0.00%) 
Hypoaesthesia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  3/37 (8.11%)  0/20 (0.00%) 
Neuropathy Peripheral * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  3/35 (8.57%)  1/37 (2.70%)  0/20 (0.00%) 
Paraesthesia * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  2/37 (5.41%)  2/20 (10.00%) 
Peripheral Sensory Neuropathy * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Sciatica * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Tremor * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Psychiatric disorders             
Anxiety * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  1/37 (2.70%)  0/20 (0.00%) 
Depressed Mood * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Depression * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Insomnia * 1  0/7 (0.00%)  1/7 (14.29%)  2/35 (5.71%)  2/35 (5.71%)  3/37 (8.11%)  1/20 (5.00%) 
Renal and urinary disorders             
Acute Kidney Injury * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  3/35 (8.57%)  0/37 (0.00%)  0/20 (0.00%) 
Dysuria * 1  0/7 (0.00%)  0/7 (0.00%)  3/35 (8.57%)  0/35 (0.00%)  1/37 (2.70%)  1/20 (5.00%) 
Haematuria * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  3/35 (8.57%)  2/37 (5.41%)  0/20 (0.00%) 
Oliguria * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Pollakiuria * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  2/20 (10.00%) 
Proteinuria * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  1/20 (5.00%) 
Renal Failure * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Reproductive system and breast disorders             
Benign Prostatic Hyperplasia * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Pelvic Pain * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Vaginal Haemorrhage * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Asthma * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Cough * 1  1/7 (14.29%)  4/7 (57.14%)  4/35 (11.43%)  11/35 (31.43%)  5/37 (13.51%)  4/20 (20.00%) 
Dysphonia * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Dyspnoea * 1  1/7 (14.29%)  0/7 (0.00%)  3/35 (8.57%)  2/35 (5.71%)  4/37 (10.81%)  1/20 (5.00%) 
Epistaxis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  3/35 (8.57%)  4/37 (10.81%)  0/20 (0.00%) 
Laryngeal Inflammation * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Nasal Congestion * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  1/37 (2.70%)  0/20 (0.00%) 
Organising Pneumonia * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Oropharyngeal Pain * 1  1/7 (14.29%)  0/7 (0.00%)  3/35 (8.57%)  3/35 (8.57%)  3/37 (8.11%)  0/20 (0.00%) 
Pneumonitis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  5/35 (14.29%)  3/37 (8.11%)  1/20 (5.00%) 
Productive Cough * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  3/35 (8.57%)  2/37 (5.41%)  0/20 (0.00%) 
Rhinorrhoea * 1  0/7 (0.00%)  1/7 (14.29%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  0/20 (0.00%) 
Upper-Airway Cough Syndrome * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/37 (5.41%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders             
Acne * 1  0/7 (0.00%)  2/7 (28.57%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Decubitus Ulcer * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/37 (0.00%)  0/20 (0.00%) 
Dermatitis * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Dermatitis Acneiform * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  3/37 (8.11%)  0/20 (0.00%) 
Dermatitis Allergic * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Dry Skin * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  2/37 (5.41%)  0/20 (0.00%) 
Ecchymosis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  2/35 (5.71%)  0/37 (0.00%)  0/20 (0.00%) 
Eczema * 1  0/7 (0.00%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  0/37 (0.00%)  2/20 (10.00%) 
Erythema * 1  1/7 (14.29%)  0/7 (0.00%)  2/35 (5.71%)  2/35 (5.71%)  1/37 (2.70%)  0/20 (0.00%) 
Ingrowing Nail * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Night Sweats * 1  1/7 (14.29%)  0/7 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  1/37 (2.70%)  1/20 (5.00%) 
Petechiae * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/37 (5.41%)  0/20 (0.00%) 
Pruritus * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  4/37 (10.81%)  0/20 (0.00%) 
Rash * 1  1/7 (14.29%)  1/7 (14.29%)  6/35 (17.14%)  8/35 (22.86%)  11/37 (29.73%)  4/20 (20.00%) 
Rash Erythematous * 1  0/7 (0.00%)  1/7 (14.29%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Rash Maculo-Papular * 1  1/7 (14.29%)  1/7 (14.29%)  1/35 (2.86%)  3/35 (8.57%)  1/37 (2.70%)  0/20 (0.00%) 
Rash Papular * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  2/37 (5.41%)  0/20 (0.00%) 
Seborrhoeic Dermatitis * 1  0/7 (0.00%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Skin Exfoliation * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Skin Lesion * 1  1/7 (14.29%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  2/37 (5.41%)  0/20 (0.00%) 
Urticaria * 1  1/7 (14.29%)  0/7 (0.00%)  2/35 (5.71%)  0/35 (0.00%)  0/37 (0.00%)  0/20 (0.00%) 
Vascular disorders             
Haematoma * 1  1/7 (14.29%)  0/7 (0.00%)  1/35 (2.86%)  5/35 (14.29%)  2/37 (5.41%)  0/20 (0.00%) 
Haemorrhage * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  1/37 (2.70%)  0/20 (0.00%) 
Hypertension * 1  0/7 (0.00%)  0/7 (0.00%)  4/35 (11.43%)  4/35 (11.43%)  2/37 (5.41%)  0/20 (0.00%) 
Hypotension * 1  1/7 (14.29%)  1/7 (14.29%)  1/35 (2.86%)  0/35 (0.00%)  2/37 (5.41%)  3/20 (15.00%) 
Pallor * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
Phlebitis * 1  1/7 (14.29%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
White Coat Hypertension * 1  0/7 (0.00%)  0/7 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/37 (0.00%)  1/20 (5.00%) 
1
Term from vocabulary, MedDRA Version 24.1
*
Indicates events were collected by non-systematic assessment
Though it was planned to administer Ibrutinib 280 milligrams (mg) to participants in case the toxicity increased, no participants received ibrutinib 280 mg in the study.
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.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Executive Medical Director
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02329847    
Other Study ID Numbers: CR106681
PCI-32765LYM1002 ( Other Identifier: Janssen Research & Development, LLC )
2014-005191-28 ( EudraCT Number )
First Submitted: December 30, 2014
First Posted: January 1, 2015
Results First Submitted: February 9, 2023
Results First Posted: June 15, 2023
Last Update Posted: June 15, 2023