Trial Outcomes & Findings for A Study of Ibrutinib in Combination With Rituximab, in Japanese Participants With Waldenstrom's Macroglobulinemia (WM) (NCT NCT04062448)

NCT ID: NCT04062448

Last Updated: 2025-05-25

Results Overview

ORR is defined as the percentage of participants achieving a best overall response of confirmed complete response (CR), very good partial response (VGPR) or partial response (PR) according to the modified sixth IWWM criteria (National Comprehensive Cancer Network \[NCCN\] version 2, 2019), as assessed by the Independent Review Committee (IRC). CR: Immunoglobulin M (IgM) in normal range, disappearance of monoclonal protein by immunofixation, no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (if present at baseline) along with no signs or symptoms attributable to Waldenstrom's Macroglobulinemia (WM); VGPR and PR: greater than or equal to (\>=) 90 percent (%) (for VGPR) and \>=50% (for PR) reduction of serum IgM, decrease in adenopathy/organomegaly (if present at baseline) on physical examination or computerized tomography (CT) scan, no new symptoms or signs of active disease.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: Up to 1 year 11 months
• Results posted on: 2025-05-25

Participant Flow

Participant milestones

Measure	Ibrutinib + Rituximab Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Overall Study STARTED	16
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Ibrutinib + Rituximab Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

A Study of Ibrutinib in Combination With Rituximab, in Japanese Participants With Waldenstrom's Macroglobulinemia (WM)

Baseline characteristics by cohort

Measure	Ibrutinib + Rituximab n=16 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Age, Continuous	67.5 years STANDARD_DEVIATION 11.21 • n=5 Participants
Age, Customized Greater Than 65	11 Participants n=5 Participants
Age, Customized Less Than and Equal to (<=) 65 years	5 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	16 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment JAPAN	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year 11 months

Population: Response evaluable analysis set included all enrolled participants who had measurable disease at baseline, received at least 1 dose of ibrutinib and who had at least 1 adequate postbaseline efficacy assessment.

ORR is defined as the percentage of participants achieving a best overall response of confirmed complete response (CR), very good partial response (VGPR) or partial response (PR) according to the modified sixth IWWM criteria (National Comprehensive Cancer Network [NCCN] version 2, 2019), as assessed by the Independent Review Committee (IRC). CR: Immunoglobulin M (IgM) in normal range, disappearance of monoclonal protein by immunofixation, no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (if present at baseline) along with no signs or symptoms attributable to Waldenstrom's Macroglobulinemia (WM); VGPR and PR: greater than or equal to (>=) 90 percent (%) (for VGPR) and >=50% (for PR) reduction of serum IgM, decrease in adenopathy/organomegaly (if present at baseline) on physical examination or computerized tomography (CT) scan, no new symptoms or signs of active disease.

Outcome measures

Measure

Ibrutinib + Rituximab n=16 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.

Overall Response Rate (ORR) According to the Modified Sixth International Workshop on Waldenstrom's Macroglobulinemia (IWWM) Criteria

87.5 percentage of participants

SECONDARY outcome

Timeframe: From the date of initial dose up to 3 years and 5 months

Population: All treated analysis set included all enrolled participants who received at least 1 dose of ibrutinib.

PFS was defined as duration from the date of initial dose of ibrutinib to the date of first documented evidence of disease progression or death, whichever occurred first regardless of the use of subsequent antineoplastic therapy prior to documented disease progression or death. Kaplan-Meier method was used for the analysis.

Outcome measures

Measure

Ibrutinib + Rituximab n=16 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.

Progression Free Survival (PFS) Assessed by Independent Review Committee

NA months The median and 95% confidence interval were not estimable due to very less number of participants with events.

SECONDARY outcome

Timeframe: Day 1 of Week 4: Predose, 1 hour, 2 hours, 4 hours, and 6 hours postdose

Population: The Pharmacokinetic (PK) evaluable analysis set included all enrolled participants who had received at least 1 dose of ibrutinib and had at least 1 post-dose PK sample. Here, n (number analyzed) refers to number of participants evaluable for specified timepoints.

Plasma concentrations of ibrutinib were reported.

Outcome measures

Measure	Ibrutinib + Rituximab n=15 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Plasma Concentrations of Ibrutinib Week 4: Predose	4.10 nanograms per milliliter (ng/mL) Standard Deviation 6.15
Plasma Concentrations of Ibrutinib Week 4: 1 hour postdose	55.6 nanograms per milliliter (ng/mL) Standard Deviation 74.6
Plasma Concentrations of Ibrutinib Week 4: 2 hours postdose	94.9 nanograms per milliliter (ng/mL) Standard Deviation 147
Plasma Concentrations of Ibrutinib Week 4: 4 hours postdose	89.9 nanograms per milliliter (ng/mL) Standard Deviation 115
Plasma Concentrations of Ibrutinib Week 4: 6 hours postdose	50.5 nanograms per milliliter (ng/mL) Standard Deviation 62.3

SECONDARY outcome

Timeframe: Day 1 of Week 4: Predose, 1 hour, 2 hours, 4 hours, and 6 hours postdose

Population: The PK evaluable analysis set included all enrolled participants who had received at least 1 dose of ibrutinib and had at least 1 post-dose PK sample. Here, n (number analyzed) refers to number of participants evaluable for specified timepoints.

Plasma concentrations of metabolite PCI-45227 were reported.

Outcome measures

Measure	Ibrutinib + Rituximab n=15 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Plasma Concentrations of Metabolite PCI-45227 Week 4: 2 hours postdose	63.9 ng/mL Standard Deviation 62.3
Plasma Concentrations of Metabolite PCI-45227 Week 4: Predose	13.7 ng/mL Standard Deviation 14.8
Plasma Concentrations of Metabolite PCI-45227 Week 4: 1 hour postdose	39.9 ng/mL Standard Deviation 42.3
Plasma Concentrations of Metabolite PCI-45227 Week 4: 4 hours postdose	79.6 ng/mL Standard Deviation 51.5
Plasma Concentrations of Metabolite PCI-45227 Week 4: 6 hour postdose	65.6 ng/mL Standard Deviation 43.1

SECONDARY outcome

Timeframe: Day 1 of Week 1

Population: All treated analysis set included all enrolled participants who received at least 1 dose of ibrutinib. Here, 'N' (number of participants analyzed) refers to participants evaluable for this outcome measure.

Number of participants with MYD88 biomarker mutations were reported. MYD88 was assessed using next generation sequencing to detect the somatic mutations in the bone marrow aspiration samples collected during the study.

Outcome measures

Measure

Ibrutinib + Rituximab n=7 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.

Number of Participants With Myeloid Differentiation Primary Response Gene 88 (MYD88) Biomarker Mutation

6 Participants

SECONDARY outcome

Timeframe: Day 1 of Week 1

Population: All treated analysis set included all enrolled participants who received at least 1 dose of ibrutinib. Here, 'N' (number of participants analyzed) refers to participants evaluable for this outcome measure.

Number of participants with CXCR-4 biomarker mutations were reported. CXCR-4 was assessed using next generation sequencing to detect the somatic mutations in the bone marrow aspiration samples collected during the study.

Outcome measures

Measure

Ibrutinib + Rituximab n=7 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.

Number of Participants With C-X-C Chemokine Receptor Type 4 (CXCR-4) Biomarker Mutations

2 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days post last dose of study drug (that is, up to 40.6 months)

Population: Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib.

An adverse event was defined as any untoward medical event that occurred in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as any AE that occurred at or after the initial administration of study intervention through the day of last dose plus 30 days.

Outcome measures

Measure

Ibrutinib + Rituximab n=16 Participants Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.

Number of Participants With Treatment- Emergent Adverse Events (TEAEs)

16 Participants

Adverse Events

Ibrutinib + Rituximab

Serious events: 4 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ibrutinib + Rituximab n=16 participants at risk Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Infections and infestations Cellulitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Pneumonia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Injury, poisoning and procedural complications Heat Illness	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Dehydration	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Arthritis Bacterial	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Covid-19	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Escherichia Bacteraemia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Pneumonia Bacterial	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Hypophagia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Renal and urinary disorders Cystitis Haemorrhagic	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.

Other adverse events

Measure	Ibrutinib + Rituximab n=16 participants at risk Treatment naive or relapsed/refractory Waldenstrom's Macroglobulinemia (WM) Japanese participants received ibrutinib 420 milligrams (mg) (3\*140 mg capsules) orally, once daily, from Day 1 of Week 1 until disease progression or unacceptable toxicity along with rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) weekly for 4 consecutive weeks (Day 1 of Weeks 1 to 4), followed by a second course of once-weekly rituximab for 4 consecutive weeks (from Week 17 to 20) after a 12-week interval.
Blood and lymphatic system disorders Anaemia	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Blood and lymphatic system disorders Iron Deficiency Anaemia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Blood and lymphatic system disorders Neutropenia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Blood and lymphatic system disorders Thrombocytopenia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Cardiac disorders Atrial Fibrillation	25.0% 4/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Cardiac disorders Palpitations	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Cardiac disorders Supraventricular Extrasystoles	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Eye disorders Dry Eye	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Eye disorders Eyelid Oedema	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Abdominal Discomfort	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Abdominal Pain Upper	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Constipation	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Dental Caries	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Diarrhoea	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Dry Mouth	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Enterocolitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Gastritis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Mouth Haemorrhage	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Periodontal Disease	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Vomiting	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
General disorders Granuloma	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
General disorders Malaise	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
General disorders Oedema Peripheral	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
General disorders Pyrexia	31.2% 5/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Hepatobiliary disorders Hepatic Function Abnormal	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Acute Sinusitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Cellulitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Cystitis	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Fungal Skin Infection	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Gastroenteritis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Hepatitis B Reactivation	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Laryngitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Nasopharyngitis	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Paronychia	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Pharyngitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Pneumonia Fungal	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Sinusitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Skin Infection	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Urethritis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Urinary Tract Infection	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Viral Infection	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Injury, poisoning and procedural complications Contusion	25.0% 4/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Injury, poisoning and procedural complications Fall	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Injury, poisoning and procedural complications Limb Injury	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Injury, poisoning and procedural complications Rib Fracture	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Alanine Aminotransferase Increased	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Aspartate Aminotransferase Increased	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Blood Bilirubin Increased	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Blood Immunoglobulin A Decreased	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Blood Immunoglobulin G Decreased	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Blood Lactate Dehydrogenase Increased	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Gamma-Glutamyltransferase Increased	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Lymphocyte Count Decreased	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Neutrophil Count Decreased	31.2% 5/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Platelet Count Decreased	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations White Blood Cell Count Decreased	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Dehydration	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Hyperuricaemia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Arthritis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Back Pain	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Osteoarthritis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Tendonitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Nervous system disorders Headache	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Nervous system disorders Neuropathy Peripheral	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Nervous system disorders Presyncope	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Renal and urinary disorders Haematuria	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Renal and urinary disorders Hypertonic Bladder	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Reproductive system and breast disorders Genital Rash	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Reproductive system and breast disorders Premenstrual Syndrome	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Reproductive system and breast disorders Prostatitis	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Reproductive system and breast disorders Prostatomegaly	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Respiratory, thoracic and mediastinal disorders Laryngeal Oedema	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Respiratory, thoracic and mediastinal disorders Pharyngeal Haemorrhage	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Respiratory, thoracic and mediastinal disorders Pulmonary Mass	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Dermatitis Acneiform	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Eczema	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Erythema	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Onychoclasis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Pruritus	18.8% 3/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Rash	37.5% 6/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Vascular disorders Hypertension	31.2% 5/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Eye disorders Normal Tension Glaucoma	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Eye disorders Retinal Haemorrhage	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Anal Fissure	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Gastrointestinal disorders Large Intestine Polyp	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Hepatobiliary disorders Bile Duct Stone	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Covid-19	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Herpes Zoster	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Infections and infestations Nail Infection	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Investigations Liver Function Test Abnormal	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Diabetes Mellitus	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Hyperkalaemia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Hypokalaemia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Metabolism and nutrition disorders Hyponatraemia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Musculoskeletal and connective tissue disorders Muscle Spasms	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic Cystadenoma	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Nervous system disorders Dizziness	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Psychiatric disorders Delirium	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Psychiatric disorders Insomnia	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Renal and urinary disorders Urinary Retention	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	12.5% 2/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Dermatitis Atopic	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Dry Skin	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Hand Dermatitis	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Nail Disorder	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Skin and subcutaneous tissue disorders Umbilical Haemorrhage	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.
Vascular disorders Internal Haemorrhage	6.2% 1/16 • All-cause mortality: From Baseline (Day 1) up to 41 months; Serious and other events: From first dose of study drug up to 30 days after last dose of study treatment ((that is, up to 40.6 months) Safety analysis set included all enrolled participants who received at least 1 dose of ibrutinib. As ibrutinib and rituximab were administered as a combination treatment, adverse events analyses was not performed per the study intervention and thus combined data are presented.

Additional Information

Director

Janssen Pharmaceutical K.K.

Phone: 844-434-4210

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER