Trial Outcomes & Findings for A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma (NCT NCT01855750)

Last Updated: 2025-02-04

Results Overview

EFS: duration from randomization date to disease progression(PD) date, relapse from complete response(CR) assessed by investigator, initiation of subsequent systemic antilymphoma therapy for either positron emission tomography(PET)-positive/ biopsy-proven residual disease upon completion of \>=6 cycles of R-CHOP therapy/death, whichever occurred first. Responses were based on Revised Response Criteria for Malignant Lymphoma. PD: any new lesion or increase by 50% of previously involved sites from nadir; PD criteria: Appearance of new nodal lesion 1.5 cm in any axis, 50% increase in sum of product of diameters(SPD) of \>1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis. CR: disappearance of all evidence of disease; CR criteria: nodal masses PET positive prior to therapy; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

838 participants

Primary outcome timeframe

Up to 5.5 years

Results posted on

2025-02-04

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Arm B: Ibrutinib+R-CHOP Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Overall Study STARTED	419	419
Overall Study Treated	416	418
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	419	419

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Arm B: Ibrutinib+R-CHOP Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Overall Study Death	78	78
Overall Study Lost to Follow-up	9	23
Overall Study Withdrawal by Subject	35	28
Overall Study Sponsor ends the study	297	290

Baseline Characteristics

A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=419 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=419 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).	Total n=838 Participants Total of all reporting groups
Age, Continuous	61.1 years STANDARD_DEVIATION 12.57 • n=5 Participants	58.8 years STANDARD_DEVIATION 13.57 • n=7 Participants	59.9 years STANDARD_DEVIATION 13.12 • n=5 Participants
Sex: Female, Male Female	198 Participants n=5 Participants	193 Participants n=7 Participants	391 Participants n=5 Participants
Sex: Female, Male Male	221 Participants n=5 Participants	226 Participants n=7 Participants	447 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	388 Participants n=5 Participants	396 Participants n=7 Participants	784 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized White	237 Participants n=5 Participants	250 Participants n=7 Participants	487 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian	166 Participants n=5 Participants	160 Participants n=7 Participants	326 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Argentina	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Australia	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment Belgium	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Brazil	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Canada	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment China	104 Participants n=5 Participants	96 Participants n=7 Participants	200 Participants n=5 Participants
Region of Enrollment Czech Republic	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Denmark	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Finland	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment France	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Germany	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Hungary	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Israel	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment Italy	24 Participants n=5 Participants	18 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment Japan	33 Participants n=5 Participants	40 Participants n=7 Participants	73 Participants n=5 Participants
Region of Enrollment Mexico	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Netherlands	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Norway	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Poland	15 Participants n=5 Participants	24 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment Russia	19 Participants n=5 Participants	34 Participants n=7 Participants	53 Participants n=5 Participants
Region of Enrollment Korea, Republic Of	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Spain	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Sweden	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Taiwan, Province Of China	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Region of Enrollment Turkey	27 Participants n=5 Participants	24 Participants n=7 Participants	51 Participants n=5 Participants
Region of Enrollment Ukraine	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment United Kingdom	14 Participants n=5 Participants	17 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment United States	40 Participants n=5 Participants	36 Participants n=7 Participants	76 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 5.5 years

Population: Intent-to-Treat (ITT) population included all randomized participants, enrolled with non-germinal center B-cell (GCB) of diffuse large B-cell lymphoma (DLBCL) subtype by immunohistochemistry (IHC), and were analyzed according to treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=419 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=419 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Event-Free Survival (EFS) - Intent-to-Treat (ITT) Population	49.64 Months Interval 47.47 to Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.	54.77 Months Interval 48.16 to 54.77

PRIMARY outcome

Timeframe: Up to approximately 4.5 years

Population: ABC population included ITT population (all randomized participants, enrolled with non-GCB of DLBCL subtype by IHC) having ABC subtype determined by gene expression profiling (GEP) (retrospectively determined from available formalin-fixed paraffin-embedded \[FFPE\] tissue specimens). Participants were analyzed according to randomized treatment.

EFS: duration from randomization date to PD date, relapse from CR assessed by investigator, initiation of subsequent systemic antilymphoma therapy for either PET-positive/ biopsy-proven residual disease upon completion of \>=6 cycles of R-CHOP therapy/death, whichever occurred first. Responses were based on Revised Response Criteria for Malignant Lymphoma. PD: any new lesion or increase by 50% of previously involved sites from nadir; PD criteria: Appearance of new nodal lesion 1.5 cm in any axis, 50% increase in SPD of \>1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis. CR: disappearance of all evidence of disease; CR criteria: nodal masses PET positive prior to therapy; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy.

Outcome measures

Outcome measures
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=285 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=282 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Event-Free Survival (EFS) - Activated B-Cell (ABC) Population	48.56 Months Interval 48.56 to Here NA signifies that the upper limit of CI was not estimable due to lesser number of events.	48.16 Months Interval 48.16 to Here NA signifies that the upper limit of CI was not estimable due to lesser number of events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: ITT population included all randomized participants, enrolled with non-GCB of DLBCL subtype by IHC, and were analyzed according to treatment to which they were randomized.

PFS was defined as the duration from the date of randomization to the date of progression, relapse from CR, or death, whichever occurred first. Responses were based on Revised Response Criteria for Malignant Lymphoma. Progressive Disease (PD): any new lesion or increase by 50% of previously involved sites from nadir; PD criteria: Appearance of new nodal lesion 1.5 centimeter (cm) in any axis, 50% increase in SPD of \>1 node or 50% increase in longest diameter of previously identified node 1 cm in short axis. CR: disappearance of all evidence of disease; CR criteria: nodal masses PET positive prior to therapy; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy.

Outcome measures

Outcome measures
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=419 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=419 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Progression-Free Survival (PFS)	48.56 Months Interval 48.56 to Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.	NA Months Interval 48.16 to Here NA signifies that median and the upper limit of Confidence Interval (CI) were not estimable due to lesser number of events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Population: ITT population included all randomized participants, who were enrolled with the non-GCB of DLBCL subtype by IHC. Participants in this population were analyzed according to the treatment to which they were randomized.

Percentage of participants with measurable disease who achieved CR were reported. CR: disappearance of all evidence of disease. CR Criteria: Complete disappearance of all disease-related symptoms; all lymph nodes and nodal masses regressed to normal size (less than or equal to \[\<=\]1.5 cm in greatest transverse diameter \[GTD\] for nodes greater than \[\>\]1.5 cm before therapy). Previous nodes of 1.1 to 1.5 cm in long axis and greater than (\>)1.0 cm in short axis before treatment decreased to \<=1.0 cm in short axis after treatment. Disappearance of all splenic and hepatic nodules and other extranodal disease; a negative positron emission tomography (PET) scan. A posttreatment residual mass of any size but PET-negative; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy.

Outcome measures

Outcome measures
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=419 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=419 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Percentage of Participants Who Achieved Complete Response (CR)	67.3 Percentage of participants	68.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to 5.5 years

Overall survival was defined as the duration from the date of randomization to the date of the participant's death. Median Overall Survival was estimated by using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=419 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=419 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Overall Survival	NA Months Here NA signifies that the median, lower and upper limit of CI were not estimable due to lesser number of events.	NA Months Here NA signifies that the median, lower and upper limit of CI were not estimable due to lesser number of events.

SECONDARY outcome

Timeframe: Up to approximately 4.5 years

Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening of participant symptoms. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life.

Outcome measures

Outcome measures
Measure	Treatment Arm B: Ibrutinib+R-CHOP n=419 Participants Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=419 Participants Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Time to Worsening in the Lymphoma Subscale of Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)	11.7 Months Interval 4.9 to 23.5	35.0 Months Interval 19.8 to Here NA signifies that the upper limit of CI was not estimable due to lesser number of events.

Adverse Events

Treatment Arm B: Ibrutinib+R-CHOP

Serious events: 221 serious events

Other events: 411 other events

Deaths: 78 deaths

Treatment Arm A: Placebo+R-CHOP

Serious events: 143 serious events

Other events: 411 other events

Deaths: 78 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Officer

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

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 in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Treatment Arm B: Ibrutinib+R-CHOP n=416 participants at risk Participants received ibrutinib 560 milligram (mg) (4\*140 mg) capsules orally once daily (Cycle 1 Day 1 to Day 21 of last cycle; 21-day cycles) along with R-CHOP (Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) as a background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus ibrutinib for 6 or 8 cycles per site preference (21 days per cycle).	Treatment Arm A: Placebo+R-CHOP n=418 participants at risk Participants received matching placebo (4 capsules) orally once daily (21-day cycles) along with R-CHOP background chemotherapy. R-CHOP regimen included rituximab 375 milligram per square meter (mg/m\^2) intravenously (IV), cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV, administered on Day 1 and prednisone 100 mg capsules orally on Days 1 to 5 of each cycle. Participants received background chemotherapy plus matching placebo for 6 or 8 cycles per site preference (21 days per cycle).
Blood and lymphatic system disorders Anaemia	41.6% 173/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	27.8% 116/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Febrile Neutropenia	9.9% 41/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.3% 22/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Leukopenia	16.8% 70/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	17.7% 74/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Lymphopenia	5.5% 23/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	8.6% 36/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	51.2% 213/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	59.3% 248/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	24.5% 102/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	12.7% 53/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Pain	8.9% 37/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	8.1% 34/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal Pain Upper	6.7% 28/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	8.1% 34/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Constipation	26.7% 111/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	26.3% 110/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	35.8% 149/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	19.4% 81/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dry Mouth	5.3% 22/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.1% 17/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Dyspepsia	6.2% 26/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.3% 22/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Mouth Ulceration	7.7% 32/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.8% 20/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	40.9% 170/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	32.3% 135/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Stomatitis	15.4% 64/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	11.2% 47/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	21.9% 91/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	14.1% 59/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Asthenia	6.7% 28/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.8% 16/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Fatigue	33.2% 138/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	24.4% 102/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Malaise	6.0% 25/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.0% 21/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Mucosal Inflammation	8.2% 34/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.5% 23/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Oedema Peripheral	11.1% 46/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.9% 29/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
General disorders Pyrexia	20.0% 83/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	16.3% 68/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	5.3% 22/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.2% 9/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	8.4% 35/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.9% 29/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Infections and infestations Urinary Tract Infection	5.8% 24/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.6% 15/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Infusion Related Reaction	5.5% 23/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.2% 26/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Alanine Aminotransferase Increased	6.0% 25/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.7% 24/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Lymphocyte Count Decreased	10.6% 44/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	10.0% 42/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Neutrophil Count Decreased	23.8% 99/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	19.4% 81/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Platelet Count Decreased	20.0% 83/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	9.1% 38/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations Weight Decreased	8.7% 36/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.3% 18/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Investigations White Blood Cell Count Decreased	25.7% 107/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	24.9% 104/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Decreased Appetite	15.4% 64/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	12.2% 51/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	5.8% 24/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.2% 9/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	18.0% 75/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.5% 23/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	5.3% 22/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	1.7% 7/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	6.7% 28/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.6% 11/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	8.2% 34/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	9.6% 40/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Bone Pain	4.1% 17/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.0% 21/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle Spasms	7.2% 30/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.3% 14/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	4.3% 18/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.7% 24/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Dysgeusia	6.2% 26/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.5% 19/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Headache	7.0% 29/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	10.3% 43/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Hypoaesthesia	6.7% 28/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.3% 22/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Neuropathy Peripheral	15.6% 65/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	8.4% 35/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	6.7% 28/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	3.8% 16/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Nervous system disorders Peripheral Sensory Neuropathy	18.5% 77/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	15.1% 63/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	9.4% 39/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	10.3% 43/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	13.2% 55/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	11.2% 47/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.2% 30/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.0% 25/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	7.7% 32/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	6.0% 25/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	16.6% 69/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	25.4% 106/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	2.6% 11/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.0% 21/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	5.3% 22/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	5.0% 21/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertension	5.5% 23/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	4.3% 18/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypotension	5.5% 23/416 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.	2.4% 10/418 • Up to 5.5 years Safety population included all randomized participants who received at least 1 dose of study drug.