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Trial record 1 of 1 for:    NCT01855750
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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01855750
Recruitment Status : Completed
First Posted : May 16, 2013
Results First Posted : March 19, 2019
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Lymphoma
Interventions Drug: Ibrutinib
Drug: Placebo
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone (or equivalent)
Enrollment 838
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description 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). 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).
Period Title: Overall Study
Started 419 419
Treated 416 [1] 418 [2]
Completed 312 313
Not Completed 107 106
Reason Not Completed
Death             68             71
Lost to Follow-up             5             9
Physician Decision             1             1
Withdrawal by Subject             33             25
[1]
3 participants not treated:2 withdrew consent and 1 not treated per Sponsor/investigator's decision.
[2]
1 participant not treated: withdrew consent.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP Total
Hide Arm/Group Description 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). 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 of all reporting groups
Overall Number of Baseline Participants 419 419 838
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 419 participants 419 participants 838 participants
61.1  (12.57) 58.8  (13.57) 59.9  (13.12)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 419 participants 838 participants
Female
198
  47.3%
193
  46.1%
391
  46.7%
Male
221
  52.7%
226
  53.9%
447
  53.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 419 participants 838 participants
Hispanic or Latino
17
   4.1%
13
   3.1%
30
   3.6%
Not Hispanic or Latino
388
  92.6%
396
  94.5%
784
  93.6%
Unknown or Not Reported
14
   3.3%
10
   2.4%
24
   2.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 419 participants 838 participants
White
237
  56.6%
250
  59.7%
487
  58.1%
Black or African American
4
   1.0%
4
   1.0%
8
   1.0%
Asian
166
  39.6%
160
  38.2%
326
  38.9%
American Indian or Alaska Native
2
   0.5%
1
   0.2%
3
   0.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Other
1
   0.2%
1
   0.2%
2
   0.2%
Unknown
0
   0.0%
0
   0.0%
0
   0.0%
Not reported
7
   1.7%
2
   0.5%
9
   1.1%
Multiple
2
   0.5%
1
   0.2%
3
   0.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 419 participants 838 participants
Argentina
1
   0.2%
1
   0.2%
2
   0.2%
Australia
12
   2.9%
8
   1.9%
20
   2.4%
Belgium
8
   1.9%
7
   1.7%
15
   1.8%
Brazil
8
   1.9%
4
   1.0%
12
   1.4%
Canada
12
   2.9%
9
   2.1%
21
   2.5%
China
104
  24.8%
96
  22.9%
200
  23.9%
Czech Republic
18
   4.3%
12
   2.9%
30
   3.6%
Denmark
5
   1.2%
6
   1.4%
11
   1.3%
Finland
6
   1.4%
8
   1.9%
14
   1.7%
France
7
   1.7%
4
   1.0%
11
   1.3%
Germany
5
   1.2%
8
   1.9%
13
   1.6%
Hungary
5
   1.2%
6
   1.4%
11
   1.3%
Israel
11
   2.6%
12
   2.9%
23
   2.7%
Italy
24
   5.7%
18
   4.3%
42
   5.0%
Japan
33
   7.9%
40
   9.5%
73
   8.7%
Mexico
2
   0.5%
1
   0.2%
3
   0.4%
Netherlands
5
   1.2%
1
   0.2%
6
   0.7%
Norway
1
   0.2%
6
   1.4%
7
   0.8%
Poland
15
   3.6%
24
   5.7%
39
   4.7%
Russia
19
   4.5%
34
   8.1%
53
   6.3%
Korea, Republic Of
14
   3.3%
11
   2.6%
25
   3.0%
Spain
5
   1.2%
7
   1.7%
12
   1.4%
Sweden
0
   0.0%
1
   0.2%
1
   0.1%
Taiwan, Province Of China
8
   1.9%
9
   2.1%
17
   2.0%
Turkey
27
   6.4%
24
   5.7%
51
   6.1%
Ukraine
10
   2.4%
9
   2.1%
19
   2.3%
United Kingdom
14
   3.3%
17
   4.1%
31
   3.7%
United States
40
   9.5%
36
   8.6%
76
   9.1%
1.Primary Outcome
Title Event-Free Survival (EFS) - Intent-to-Treat (ITT) Population
Hide Description 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.
Time Frame Up to approximately 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 419 419
Median (95% Confidence Interval)
Unit of Measure: Months
48.56 [1] 
(48.56 to NA)
NA [2] 
(48.16 to NA)
[1]
Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.
[2]
Here NA signifies that median and the upper limit of CI were not estimable due to lesser number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5906
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.934
Confidence Interval (2-Sided) 95%
0.726 to 1.200
Estimation Comments [Not Specified]
2.Primary Outcome
Title Event-Free Survival (EFS) - Activated B-Cell (ABC) Population
Hide Description 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.
Time Frame Up to approximately 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 285 282
Median (95% Confidence Interval)
Unit of Measure: Months
48.56 [1] 
(48.56 to NA)
48.16 [1] 
(48.16 to NA)
[1]
Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7311
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.949
Confidence Interval (2-Sided) 95%
0.704 to 1.279
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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.
Time Frame Up to approximately 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 419 419
Median (95% Confidence Interval)
Unit of Measure: Months
48.56 [1] 
(48.56 to NA)
NA [2] 
(48.16 to NA)
[1]
Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.
[2]
Here NA signifies that median and the upper limit of Confidence Interval (CI) were not estimable due to lesser number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5027
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.917
Confidence Interval (2-Sided) 95%
0.710 to 1.183
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Who Achieved Complete Response (CR)
Hide Description 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.
Time Frame Up to approximately 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 419 419
Measure Type: Number
Unit of Measure: Percentage of participants
67.3 68.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8229
Comments [Not Specified]
Method Cochran-Mantel-Haenszel (CMH) Chi‑square
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.967
Confidence Interval (2-Sided) 95%
0.722 to 1.296
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Overall Survival
Hide Description 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.
Time Frame Up to approximately 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 419 419
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Here NA signifies that the median, lower and upper limit of Confidence Interval (CI) were not estimable due to lesser number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9593
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.991
Confidence Interval (2-Sided) 95%
0.712 to 1.380
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Worsening in the Lymphoma Subscale of Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
Hide Description 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.
Time Frame Up to approximately 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description:
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).
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 Number of Participants Analyzed 419 419
Median (95% Confidence Interval)
Unit of Measure: Months
11.7
(4.9 to 23.5)
35.0 [1] 
(19.8 to NA)
[1]
Here NA signifies that the upper limit of Confidence Interval (CI) was not estimable due to lesser number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.358
Confidence Interval (2-Sided) 95%
1.115 to 1.654
Estimation Comments [Not Specified]
Time Frame Approximately 4.5 years
Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose of study drug.
 
Arm/Group Title Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Hide Arm/Group Description 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). 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).
All-Cause Mortality
Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Affected / at Risk (%) Affected / at Risk (%)
Total   68/416 (16.35%)   71/418 (16.99%) 
Hide Serious Adverse Events
Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Affected / at Risk (%) Affected / at Risk (%)
Total   221/416 (53.13%)   142/418 (33.97%) 
Blood and lymphatic system disorders     
Anaemia * 1  15/416 (3.61%)  5/418 (1.20%) 
Febrile Neutropenia * 1  78/416 (18.75%)  44/418 (10.53%) 
Leukopenia * 1  4/416 (0.96%)  2/418 (0.48%) 
Lymphopenia * 1  1/416 (0.24%)  0/418 (0.00%) 
Neutropenia * 1  17/416 (4.09%)  13/418 (3.11%) 
Pancytopenia * 1  0/416 (0.00%)  1/418 (0.24%) 
Thrombocytopenia * 1  9/416 (2.16%)  1/418 (0.24%) 
Cardiac disorders     
Acute Coronary Syndrome * 1  1/416 (0.24%)  0/418 (0.00%) 
Acute Myocardial Infarction * 1  1/416 (0.24%)  1/418 (0.24%) 
Angina Pectoris * 1  2/416 (0.48%)  1/418 (0.24%) 
Arteriosclerosis Coronary Artery * 1  1/416 (0.24%)  0/418 (0.00%) 
Atrial Fibrillation * 1  13/416 (3.13%)  1/418 (0.24%) 
Atrial Flutter * 1  1/416 (0.24%)  0/418 (0.00%) 
Cardiac Arrest * 1  1/416 (0.24%)  0/418 (0.00%) 
Cardiac Failure * 1  2/416 (0.48%)  5/418 (1.20%) 
Cardiac Failure Acute * 1  1/416 (0.24%)  1/418 (0.24%) 
Cardiac Failure Congestive * 1  2/416 (0.48%)  1/418 (0.24%) 
Cardiomyopathy * 1  0/416 (0.00%)  1/418 (0.24%) 
Cardiopulmonary Failure * 1  0/416 (0.00%)  1/418 (0.24%) 
Left Ventricular Dysfunction * 1  0/416 (0.00%)  1/418 (0.24%) 
Myocardial Infarction * 1  1/416 (0.24%)  1/418 (0.24%) 
Myocardial Ischaemia * 1  2/416 (0.48%)  0/418 (0.00%) 
Sinus Node Dysfunction * 1  1/416 (0.24%)  0/418 (0.00%) 
Supraventricular Tachycardia * 1  0/416 (0.00%)  1/418 (0.24%) 
Tachycardia * 1  2/416 (0.48%)  0/418 (0.00%) 
Ventricular Tachycardia * 1  1/416 (0.24%)  0/418 (0.00%) 
Congenital, familial and genetic disorders     
Congenital Neuropathy * 1  0/416 (0.00%)  1/418 (0.24%) 
Pyloric Stenosis * 1  1/416 (0.24%)  0/418 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  1/416 (0.24%)  0/418 (0.00%) 
Eye disorders     
Eye Haemorrhage * 1  1/416 (0.24%)  0/418 (0.00%) 
Glaucoma * 1  1/416 (0.24%)  0/418 (0.00%) 
Retinal Detachment * 1  0/416 (0.00%)  1/418 (0.24%) 
Gastrointestinal disorders     
Abdominal Pain * 1  2/416 (0.48%)  2/418 (0.48%) 
Colitis * 1  3/416 (0.72%)  0/418 (0.00%) 
Constipation * 1  1/416 (0.24%)  0/418 (0.00%) 
Diarrhoea * 1  15/416 (3.61%)  4/418 (0.96%) 
Diverticular Perforation * 1  1/416 (0.24%)  0/418 (0.00%) 
Duodenal Ulcer Haemorrhage * 1  1/416 (0.24%)  0/418 (0.00%) 
Dyspepsia * 1  0/416 (0.00%)  1/418 (0.24%) 
Enteritis * 1  1/416 (0.24%)  0/418 (0.00%) 
Gastric Haemorrhage * 1  2/416 (0.48%)  1/418 (0.24%) 
Gastric Perforation * 1  1/416 (0.24%)  1/418 (0.24%) 
Gastrointestinal Haemorrhage * 1  1/416 (0.24%)  1/418 (0.24%) 
Gastrooesophageal Reflux Disease * 1  0/416 (0.00%)  1/418 (0.24%) 
Ileus * 1  1/416 (0.24%)  2/418 (0.48%) 
Intestinal Obstruction * 1  2/416 (0.48%)  0/418 (0.00%) 
Lower Gastrointestinal Haemorrhage * 1  1/416 (0.24%)  0/418 (0.00%) 
Mechanical Ileus * 1  0/416 (0.00%)  1/418 (0.24%) 
Nausea * 1  6/416 (1.44%)  3/418 (0.72%) 
Neutropenic Colitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Obstruction Gastric * 1  0/416 (0.00%)  1/418 (0.24%) 
Oesophagitis * 1  1/416 (0.24%)  1/418 (0.24%) 
Pancreatitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Rectal Haemorrhage * 1  1/416 (0.24%)  0/418 (0.00%) 
Small Intestinal Obstruction * 1  0/416 (0.00%)  1/418 (0.24%) 
Small Intestinal Perforation * 1  1/416 (0.24%)  1/418 (0.24%) 
Stomatitis * 1  2/416 (0.48%)  0/418 (0.00%) 
Vomiting * 1  8/416 (1.92%)  2/418 (0.48%) 
General disorders     
Asthenia * 1  2/416 (0.48%)  1/418 (0.24%) 
Chest Pain * 1  1/416 (0.24%)  0/418 (0.00%) 
Device Related Thrombosis * 1  0/416 (0.00%)  1/418 (0.24%) 
Drowning * 1  0/416 (0.00%)  1/418 (0.24%) 
Fatigue * 1  5/416 (1.20%)  1/418 (0.24%) 
General Physical Health Deterioration * 1  2/416 (0.48%)  1/418 (0.24%) 
Injection Site Extravasation * 1  1/416 (0.24%)  0/418 (0.00%) 
Malaise * 1  1/416 (0.24%)  0/418 (0.00%) 
Mucosal Inflammation * 1  3/416 (0.72%)  0/418 (0.00%) 
Multiple Organ Dysfunction Syndrome * 1  1/416 (0.24%)  1/418 (0.24%) 
Non-Cardiac Chest Pain * 1  0/416 (0.00%)  1/418 (0.24%) 
Oedema Peripheral * 1  1/416 (0.24%)  1/418 (0.24%) 
Pain * 1  1/416 (0.24%)  0/418 (0.00%) 
Pyrexia * 1  12/416 (2.88%)  11/418 (2.63%) 
Sudden Death * 1  2/416 (0.48%)  2/418 (0.48%) 
Hepatobiliary disorders     
Cholangitis * 1  0/416 (0.00%)  1/418 (0.24%) 
Cholecystitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Hepatic Failure * 1  2/416 (0.48%)  0/418 (0.00%) 
Hepatic Function Abnormal * 1  1/416 (0.24%)  2/418 (0.48%) 
Infections and infestations     
Arteritis Infective * 1  1/416 (0.24%)  0/418 (0.00%) 
Aspergillus Infection * 1  2/416 (0.48%)  0/418 (0.00%) 
Atypical Pneumonia * 1  1/416 (0.24%)  0/418 (0.00%) 
Bacteraemia * 1  1/416 (0.24%)  0/418 (0.00%) 
Brain Abscess * 1  1/416 (0.24%)  0/418 (0.00%) 
Bronchitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Bronchopulmonary Aspergillosis * 1  2/416 (0.48%)  1/418 (0.24%) 
Cellulitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Cerebral Aspergillosis * 1  1/416 (0.24%)  0/418 (0.00%) 
Clostridial Infection * 1  2/416 (0.48%)  0/418 (0.00%) 
Cryptococcal Fungaemia * 1  1/416 (0.24%)  0/418 (0.00%) 
Cytomegalovirus Gastrointestinal Infection * 1  0/416 (0.00%)  1/418 (0.24%) 
Device Related Infection * 1  4/416 (0.96%)  1/418 (0.24%) 
Enterococcal Sepsis * 1  1/416 (0.24%)  0/418 (0.00%) 
Erysipelas * 1  0/416 (0.00%)  1/418 (0.24%) 
Gastroenteritis * 1  1/416 (0.24%)  0/418 (0.00%) 
Gastroenteritis Bacterial * 1  0/416 (0.00%)  1/418 (0.24%) 
Haemophilus Infection * 1  0/416 (0.00%)  1/418 (0.24%) 
Hepatitis B * 1  1/416 (0.24%)  1/418 (0.24%) 
Hepatitis B Reactivation * 1  0/416 (0.00%)  1/418 (0.24%) 
Herpes Zoster * 1  2/416 (0.48%)  3/418 (0.72%) 
Incision Site Infection * 1  0/416 (0.00%)  1/418 (0.24%) 
Infection * 1  3/416 (0.72%)  2/418 (0.48%) 
Klebsiella Sepsis * 1  0/416 (0.00%)  1/418 (0.24%) 
Lower Respiratory Tract Infection * 1  1/416 (0.24%)  0/418 (0.00%) 
Lower Respiratory Tract Infection Fungal * 1  1/416 (0.24%)  0/418 (0.00%) 
Lung Abscess * 1  1/416 (0.24%)  0/418 (0.00%) 
Lung Infection * 1  14/416 (3.37%)  7/418 (1.67%) 
Lymph Gland Infection * 1  0/416 (0.00%)  1/418 (0.24%) 
Mucosal Infection * 1  1/416 (0.24%)  0/418 (0.00%) 
Neutropenic Infection * 1  2/416 (0.48%)  1/418 (0.24%) 
Neutropenic Sepsis * 1  1/416 (0.24%)  2/418 (0.48%) 
Peritonitis * 1  1/416 (0.24%)  1/418 (0.24%) 
Pharyngitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Pneumocystis Jirovecii Pneumonia * 1  3/416 (0.72%)  0/418 (0.00%) 
Pneumonia * 1  28/416 (6.73%)  14/418 (3.35%) 
Pneumonia Cryptococcal * 1  1/416 (0.24%)  0/418 (0.00%) 
Pneumonia Cytomegaloviral * 1  1/416 (0.24%)  0/418 (0.00%) 
Pneumonia Klebsiella * 1  2/416 (0.48%)  0/418 (0.00%) 
Pneumonia Respiratory Syncytial Viral * 1  0/416 (0.00%)  1/418 (0.24%) 
Pseudomembranous Colitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Pulmonary Mycosis * 1  1/416 (0.24%)  0/418 (0.00%) 
Respiratory Syncytial Virus Infection * 1  1/416 (0.24%)  0/418 (0.00%) 
Respiratory Tract Infection * 1  1/416 (0.24%)  0/418 (0.00%) 
Respiratory Tract Infection Bacterial * 1  1/416 (0.24%)  0/418 (0.00%) 
Respiratory Tract Infection Fungal * 1  1/416 (0.24%)  0/418 (0.00%) 
Sepsis * 1  7/416 (1.68%)  3/418 (0.72%) 
Septic Shock * 1  5/416 (1.20%)  1/418 (0.24%) 
Sialoadenitis * 1  0/416 (0.00%)  1/418 (0.24%) 
Sinusitis * 1  0/416 (0.00%)  2/418 (0.48%) 
Upper Respiratory Tract Infection * 1  3/416 (0.72%)  1/418 (0.24%) 
Urinary Tract Infection * 1  5/416 (1.20%)  3/418 (0.72%) 
Urosepsis * 1  1/416 (0.24%)  1/418 (0.24%) 
Viral Infection * 1  2/416 (0.48%)  0/418 (0.00%) 
Viral Upper Respiratory Tract Infection * 1  1/416 (0.24%)  0/418 (0.00%) 
Wound Infection * 1  0/416 (0.00%)  1/418 (0.24%) 
Injury, poisoning and procedural complications     
Compression Fracture * 1  1/416 (0.24%)  0/418 (0.00%) 
Femoral Neck Fracture * 1  0/416 (0.00%)  1/418 (0.24%) 
Fibula Fracture * 1  1/416 (0.24%)  0/418 (0.00%) 
Hip Fracture * 1  0/416 (0.00%)  2/418 (0.48%) 
Humerus Fracture * 1  0/416 (0.00%)  1/418 (0.24%) 
Infusion Related Reaction * 1  1/416 (0.24%)  0/418 (0.00%) 
Lumbar Vertebral Fracture * 1  1/416 (0.24%)  0/418 (0.00%) 
Postoperative Thrombosis * 1  1/416 (0.24%)  0/418 (0.00%) 
Pubis Fracture * 1  1/416 (0.24%)  0/418 (0.00%) 
Skull Fractured Base * 1  1/416 (0.24%)  0/418 (0.00%) 
Spinal Compression Fracture * 1  1/416 (0.24%)  0/418 (0.00%) 
Subdural Haematoma * 1  0/416 (0.00%)  3/418 (0.72%) 
Investigations     
Alanine Aminotransferase Increased * 1  0/416 (0.00%)  1/418 (0.24%) 
C-Reactive Protein Increased * 1  0/416 (0.00%)  1/418 (0.24%) 
Neutrophil Count Decreased * 1  5/416 (1.20%)  2/418 (0.48%) 
Platelet Count Decreased * 1  2/416 (0.48%)  0/418 (0.00%) 
Weight Decreased * 1  1/416 (0.24%)  0/418 (0.00%) 
White Blood Cell Count Decreased * 1  3/416 (0.72%)  0/418 (0.00%) 
White Blood Cell Count Increased * 1  1/416 (0.24%)  0/418 (0.00%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  0/416 (0.00%)  2/418 (0.48%) 
Dehydration * 1  8/416 (1.92%)  2/418 (0.48%) 
Diabetes Mellitus * 1  0/416 (0.00%)  1/418 (0.24%) 
Fluid Overload * 1  1/416 (0.24%)  0/418 (0.00%) 
Hyperglycaemia * 1  0/416 (0.00%)  1/418 (0.24%) 
Hypokalaemia * 1  4/416 (0.96%)  0/418 (0.00%) 
Hyponatraemia * 1  3/416 (0.72%)  1/418 (0.24%) 
Hypophagia * 1  1/416 (0.24%)  1/418 (0.24%) 
Hypoproteinaemia * 1  1/416 (0.24%)  0/418 (0.00%) 
Ketoacidosis * 1  0/416 (0.00%)  1/418 (0.24%) 
Tumour Lysis Syndrome * 1  1/416 (0.24%)  0/418 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/416 (0.24%)  0/418 (0.00%) 
Back Pain * 1  1/416 (0.24%)  0/418 (0.00%) 
Chondrocalcinosis Pyrophosphate * 1  1/416 (0.24%)  0/418 (0.00%) 
Flank Pain * 1  0/416 (0.00%)  1/418 (0.24%) 
Muscular Weakness * 1  2/416 (0.48%)  0/418 (0.00%) 
Myalgia * 1  1/416 (0.24%)  0/418 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Angioimmunoblastic T-Cell Lymphoma * 1  0/416 (0.00%)  1/418 (0.24%) 
Basal Cell Carcinoma * 1  1/416 (0.24%)  0/418 (0.00%) 
Colorectal Adenocarcinoma * 1  0/416 (0.00%)  1/418 (0.24%) 
Laryngeal Cancer Metastatic * 1  1/416 (0.24%)  0/418 (0.00%) 
Malignant Melanoma * 1  1/416 (0.24%)  0/418 (0.00%) 
Squamous Cell Carcinoma of Skin * 1  1/416 (0.24%)  0/418 (0.00%) 
Nervous system disorders     
Altered State of Consciousness * 1  1/416 (0.24%)  0/418 (0.00%) 
Central Nervous System Inflammation * 1  0/416 (0.00%)  1/418 (0.24%) 
Cerebral Haemorrhage * 1  1/416 (0.24%)  0/418 (0.00%) 
Cerebral Infarction * 1  0/416 (0.00%)  1/418 (0.24%) 
Cerebrospinal Fluid Leakage * 1  0/416 (0.00%)  1/418 (0.24%) 
Cerebrovascular Disorder * 1  1/416 (0.24%)  0/418 (0.00%) 
Dizziness Postural * 1  1/416 (0.24%)  0/418 (0.00%) 
Epilepsy * 1  0/416 (0.00%)  1/418 (0.24%) 
Febrile Convulsion * 1  1/416 (0.24%)  0/418 (0.00%) 
Haemorrhage Intracranial * 1  2/416 (0.48%)  0/418 (0.00%) 
Hemiparesis * 1  0/416 (0.00%)  1/418 (0.24%) 
Intracranial Hypotension * 1  0/416 (0.00%)  1/418 (0.24%) 
Nerve Compression * 1  0/416 (0.00%)  1/418 (0.24%) 
Polyneuropathy * 1  1/416 (0.24%)  0/418 (0.00%) 
Sciatica * 1  1/416 (0.24%)  0/418 (0.00%) 
Seizure * 1  1/416 (0.24%)  0/418 (0.00%) 
Syncope * 1  5/416 (1.20%)  1/418 (0.24%) 
Psychiatric disorders     
Bipolar I Disorder * 1  0/416 (0.00%)  1/418 (0.24%) 
Confusional State * 1  0/416 (0.00%)  1/418 (0.24%) 
Suicidal Ideation * 1  1/416 (0.24%)  0/418 (0.00%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  4/416 (0.96%)  1/418 (0.24%) 
Cystitis Haemorrhagic * 1  1/416 (0.24%)  0/418 (0.00%) 
Dysuria * 1  1/416 (0.24%)  0/418 (0.00%) 
Pollakiuria * 1  1/416 (0.24%)  0/418 (0.00%) 
Renal Failure * 1  1/416 (0.24%)  2/418 (0.48%) 
Urinary Retention * 1  1/416 (0.24%)  0/418 (0.00%) 
Reproductive system and breast disorders     
Vaginal Fistula * 1  1/416 (0.24%)  0/418 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure * 1  0/416 (0.00%)  1/418 (0.24%) 
Alveolitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Atelectasis * 1  0/416 (0.00%)  1/418 (0.24%) 
Diffuse Alveolar Damage * 1  1/416 (0.24%)  0/418 (0.00%) 
Dyspnoea * 1  1/416 (0.24%)  1/418 (0.24%) 
Hypoxia * 1  1/416 (0.24%)  0/418 (0.00%) 
Interstitial Lung Disease * 1  7/416 (1.68%)  4/418 (0.96%) 
Obliterative Bronchiolitis * 1  0/416 (0.00%)  1/418 (0.24%) 
Pharyngeal Haemorrhage * 1  0/416 (0.00%)  1/418 (0.24%) 
Pleural Effusion * 1  1/416 (0.24%)  1/418 (0.24%) 
Pneumonia Aspiration * 1  1/416 (0.24%)  0/418 (0.00%) 
Pneumonitis * 1  6/416 (1.44%)  3/418 (0.72%) 
Pulmonary Embolism * 1  1/416 (0.24%)  3/418 (0.72%) 
Pulmonary Mass * 1  1/416 (0.24%)  0/418 (0.00%) 
Respiratory Failure * 1  2/416 (0.48%)  1/418 (0.24%) 
Sinus Polyp * 1  1/416 (0.24%)  0/418 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis Allergic * 1  1/416 (0.24%)  0/418 (0.00%) 
Vascular disorders     
Aortic Aneurysm * 1  1/416 (0.24%)  0/418 (0.00%) 
Arteriosclerosis * 1  1/416 (0.24%)  0/418 (0.00%) 
Deep Vein Thrombosis * 1  1/416 (0.24%)  2/418 (0.48%) 
Embolism * 1  0/416 (0.00%)  1/418 (0.24%) 
Hypotension * 1  6/416 (1.44%)  1/418 (0.24%) 
Shock Haemorrhagic * 1  1/416 (0.24%)  0/418 (0.00%) 
Thrombophlebitis * 1  1/416 (0.24%)  0/418 (0.00%) 
Vena Cava Thrombosis * 1  0/416 (0.00%)  1/418 (0.24%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment Arm B: Ibrutinib+R-CHOP Treatment Arm A: Placebo+R-CHOP
Affected / at Risk (%) Affected / at Risk (%)
Total   411/416 (98.80%)   411/418 (98.33%) 
Blood and lymphatic system disorders     
Anaemia * 1  173/416 (41.59%)  116/418 (27.75%) 
Febrile Neutropenia * 1  41/416 (9.86%)  22/418 (5.26%) 
Leukopenia * 1  70/416 (16.83%)  74/418 (17.70%) 
Lymphopenia * 1  23/416 (5.53%)  36/418 (8.61%) 
Neutropenia * 1  213/416 (51.20%)  248/418 (59.33%) 
Thrombocytopenia * 1  102/416 (24.52%)  53/418 (12.68%) 
Gastrointestinal disorders     
Abdominal Pain * 1  37/416 (8.89%)  34/418 (8.13%) 
Abdominal Pain Upper * 1  28/416 (6.73%)  34/418 (8.13%) 
Constipation * 1  111/416 (26.68%)  110/418 (26.32%) 
Diarrhoea * 1  149/416 (35.82%)  81/418 (19.38%) 
Dry Mouth * 1  22/416 (5.29%)  17/418 (4.07%) 
Dyspepsia * 1  26/416 (6.25%)  22/418 (5.26%) 
Mouth Ulceration * 1  32/416 (7.69%)  20/418 (4.78%) 
Nausea * 1  170/416 (40.87%)  135/418 (32.30%) 
Stomatitis * 1  64/416 (15.38%)  47/418 (11.24%) 
Vomiting * 1  91/416 (21.88%)  59/418 (14.11%) 
General disorders     
Asthenia * 1  28/416 (6.73%)  16/418 (3.83%) 
Fatigue * 1  138/416 (33.17%)  102/418 (24.40%) 
Malaise * 1  25/416 (6.01%)  21/418 (5.02%) 
Mucosal Inflammation * 1  34/416 (8.17%)  23/418 (5.50%) 
Oedema Peripheral * 1  46/416 (11.06%)  29/418 (6.94%) 
Pyrexia * 1  83/416 (19.95%)  68/418 (16.27%) 
Infections and infestations     
Pneumonia * 1  22/416 (5.29%)  9/418 (2.15%) 
Upper Respiratory Tract Infection * 1  35/416 (8.41%)  29/418 (6.94%) 
Urinary Tract Infection * 1  24/416 (5.77%)  15/418 (3.59%) 
Injury, poisoning and procedural complications     
Infusion Related Reaction * 1  23/416 (5.53%)  26/418 (6.22%) 
Investigations     
Alanine Aminotransferase Increased * 1  25/416 (6.01%)  24/418 (5.74%) 
Lymphocyte Count Decreased * 1  44/416 (10.58%)  42/418 (10.05%) 
Neutrophil Count Decreased * 1  99/416 (23.80%)  81/418 (19.38%) 
Platelet Count Decreased * 1  83/416 (19.95%)  38/418 (9.09%) 
Weight Decreased * 1  36/416 (8.65%)  18/418 (4.31%) 
White Blood Cell Count Decreased * 1  107/416 (25.72%)  104/418 (24.88%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  64/416 (15.38%)  51/418 (12.20%) 
Hypoalbuminaemia * 1  24/416 (5.77%)  9/418 (2.15%) 
Hypokalaemia * 1  75/416 (18.03%)  23/418 (5.50%) 
Hypomagnesaemia * 1  22/416 (5.29%)  7/418 (1.67%) 
Hyponatraemia * 1  28/416 (6.73%)  11/418 (2.63%) 
Musculoskeletal and connective tissue disorders     
Back Pain * 1  34/416 (8.17%)  40/418 (9.57%) 
Bone Pain * 1  17/416 (4.09%)  21/418 (5.02%) 
Muscle Spasms * 1  30/416 (7.21%)  14/418 (3.35%) 
Myalgia * 1  18/416 (4.33%)  24/418 (5.74%) 
Nervous system disorders     
Dysgeusia * 1  26/416 (6.25%)  19/418 (4.55%) 
Headache * 1  29/416 (6.97%)  43/418 (10.29%) 
Hypoaesthesia * 1  28/416 (6.73%)  22/418 (5.26%) 
Neuropathy Peripheral * 1  65/416 (15.63%)  35/418 (8.37%) 
Paraesthesia * 1  28/416 (6.73%)  16/418 (3.83%) 
Peripheral Sensory Neuropathy * 1  77/416 (18.51%)  63/418 (15.07%) 
Psychiatric disorders     
Insomnia * 1  39/416 (9.38%)  43/418 (10.29%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  55/416 (13.22%)  47/418 (11.24%) 
Dyspnoea * 1  30/416 (7.21%)  25/418 (5.98%) 
Oropharyngeal Pain * 1  32/416 (7.69%)  25/418 (5.98%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  69/416 (16.59%)  106/418 (25.36%) 
Pruritus * 1  11/416 (2.64%)  21/418 (5.02%) 
Rash * 1  22/416 (5.29%)  21/418 (5.02%) 
Vascular disorders     
Hypertension * 1  23/416 (5.53%)  18/418 (4.31%) 
Hypotension * 1  23/416 (5.53%)  10/418 (2.39%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
More older participants and participants with comorbidities randomized to ibrutinib+R-CHOP compared to placebo+R-CHOP, led to confounded results. In Ibrutinib+R-CHOP, upper limit of 95% CI was not estimable which limited interpretation of median EFS.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Officer
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01855750    
Other Study ID Numbers: CR102118
PCI-32765DBL3001 ( Other Identifier: Janssen Research & Development, LLC )
U1111-1139-6222 ( Other Identifier: Universal Trial Number )
2013-000959-40 ( EudraCT Number )
First Submitted: May 14, 2013
First Posted: May 16, 2013
Results First Submitted: February 22, 2019
Results First Posted: March 19, 2019
Last Update Posted: February 5, 2020