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
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01855750
Collaborator
Pharmacyclics LLC. (Industry)
838
206
2
67
4.1
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate if ibrutinib administered in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the clinical outcome in newly diagnosed patients with non-germinal center B-cell subtype (GCB) of diffuse large B-cell lymphoma (DLBCL) selected by immunohistochemistry (IHC) or newly diagnosed patients with activated B cell-like (ABC) subtype of DLBCL identified by gene expression profiling (GEP) or both populations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a randomized (individuals assigned to study treatment by chance), double-blind (individuals and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to compare the efficacy and safety of ibrutinib in combination with R-CHOP versus R-CHOP alone in adult patients newly diagnosed non-GCB DLBCL selected by IHC or newly diagnosed patients with ABC subtype of DLBCL identified by GEP or both populations. The study will include screening, active treatment, and posttreatment follow-up phases. The study will end when 50% of participants have died or 5 years after the last participant is randomized or the sponsor terminates the study, whichever occurs first. Approximately 800 participants will be randomly assigned in a 1:1 ratio to receive either placebo+R-CHOP (treatment arm A) or ibrutinib+R-CHOP (treatment arm B). All participants will receive R-CHOP as background therapy for 6 or 8 cycles (21 days per cycle) prespecified according to local practice. After 4 treatment cycles, an interim response assessment will be performed to evaluate disease progression for each participant. Participants with progressive disease or relapsed disease after complete response will be discontinued from treatment. Participants who discontinue R-CHOP without disease progression will continue study drug (placebo or ibrutinib) until 6 or 8 cycles are completed, disease progression, or unacceptable toxicity, whichever occurs first. After completion of study drug, participants will undergo assessment of tumor response based on the Revised Response Criteria for Malignant Lymphoma. Participants with documented residual disease upon completion of at least 6 cycles of R-CHOP therapy are considered eligible to initiate subsequent antilymphoma therapy. Serial pharmacokinetic samples will be collected before and after dosing, and safety will be monitored throughout the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
838 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
Actual Study Start Date
:
Sep 3, 2013
Actual Primary Completion Date
:
Feb 26, 2018
Actual Study Completion Date
:
Apr 5, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Treatment Arm A: placebo + R-CHOP Treatment Arm A = placebo + R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) |
Drug: Placebo
4 matched capsules administered by mouth once daily (21-day cycles)
Drug: Rituximab
375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Doxorubicin
50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Vincristine
1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Prednisone (or equivalent)
100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle
|
| Experimental: Treatment Arm B: ibrutinib + R-CHOP Treatment Arm B = ibrutinib + R-CHOP |
Drug: Ibrutinib
560 mg capsules administered by mouth once daily (21-day cycles)
Drug: Rituximab
375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Doxorubicin
50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Vincristine
1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
Drug: Prednisone (or equivalent)
100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle
|
Outcome Measures
Primary Outcome Measures
- Event-Free Survival (EFS) - Intent-to-Treat (ITT) Population [Up to 5.5 years]
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.
- Event-Free Survival (EFS) - Activated B-Cell (ABC) Population [Up to approximately 4.5 years]
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.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [Up to approximately 4.5 years]
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.
- Percentage of Participants Who Achieved Complete Response (CR) [Up to approximately 4.5 years]
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.
- Overall Survival [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.
- Time to Worsening in the Lymphoma Subscale of Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
No prior treatment for diffuse B-cell lymphoma (DLBCL)
-
Histologically-confirmed non-germinal center B-cell subtype DLBCL
-
Stage II (not candidates for local x-ray therapy), III, or IV disease by the Ann Arbor Classification
-
At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
-
Revised International Prognostic Index score of >=1
-
Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2
-
Hematology and biochemical laboratory values within protocol-defined parameters prior to random assignment and at baseline
-
Left ventricular ejection fraction within institutional normal limits, as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
-
Agrees to protocol-defined use of effective contraception (for women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose of study drug, whichever is later; for men, these restrictions apply for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later)
-
Men must agree to not donate sperm during and after the study for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later
-
Women of childbearing potential must have a negative serum or urine pregnancy test at screening
Exclusion Criteria:
-
Major surgery within 4 weeks of random assignment
-
Known central nervous system or primary mediastinal lymphoma
-
Prior history of indolent lymphoma
-
Diagnosed or treated for malignancy other than DLBCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease
-
History of stroke or intracranial hemorrhage within 6 months prior to random assignment
-
Requires anticoagulation with warfarin or equivalent vitamin K antagonists
-
Requires treatment with strong CYP3A inhibitors
-
Prior anthracycline use >=150 mg/m2
-
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
-
Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
-
Women who are pregnant or breastfeeding
-
Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson | Arizona | United States | ||
| 2 | Greenbrae | California | United States | ||
| 3 | La Jolla | California | United States | ||
| 4 | Los Angeles | California | United States | ||
| 5 | Salinas | California | United States | ||
| 6 | Stanford | California | United States | ||
| 7 | Danbury | Connecticut | United States | ||
| 8 | Hartford | Connecticut | United States | ||
| 9 | Washington | District of Columbia | United States | ||
| 10 | Atlanta | Georgia | United States | ||
| 11 | Marietta | Georgia | United States | ||
| 12 | Peoria | Illinois | United States | ||
| 13 | Fort Wayne | Indiana | United States | ||
| 14 | Goshen | Indiana | United States | ||
| 15 | Indianapolis | Indiana | United States | ||
| 16 | Topeka | Kansas | United States | ||
| 17 | Louisville | Kentucky | United States | ||
| 18 | Baton Rouge | Louisiana | United States | ||
| 19 | New Orleans | Louisiana | United States | ||
| 20 | Baltimore | Maryland | United States | ||
| 21 | Bethesda | Maryland | United States | ||
| 22 | Boston | Massachusetts | United States | ||
| 23 | Ann Arbor | Michigan | United States | ||
| 24 | Saint Louis | Missouri | United States | ||
| 25 | Omaha | Nebraska | United States | ||
| 26 | Hackensack | New Jersey | United States | ||
| 27 | New Brunswick | New Jersey | United States | ||
| 28 | Bronx | New York | United States | ||
| 29 | Fresh Meadows | New York | United States | ||
| 30 | Johnson City | New York | United States | ||
| 31 | Mineola | New York | United States | ||
| 32 | New York | New York | United States | ||
| 33 | Rochester | New York | United States | ||
| 34 | Charlotte | North Carolina | United States | ||
| 35 | Greenville | North Carolina | United States | ||
| 36 | Hickory | North Carolina | United States | ||
| 37 | Columbus | Ohio | United States | ||
| 38 | Portland | Oregon | United States | ||
| 39 | North Charleston | South Carolina | United States | ||
| 40 | Nashville | Tennessee | United States | ||
| 41 | Houston | Texas | United States | ||
| 42 | Temple | Texas | United States | ||
| 43 | Burlington | Vermont | United States | ||
| 44 | Seattle | Washington | United States | ||
| 45 | Buenos Aires | Argentina | |||
| 46 | Ciudad Autonoma de Buenos Aires | Argentina | |||
| 47 | Ciudad de Buenos Aires | Argentina | |||
| 48 | Adelaide | Australia | |||
| 49 | Concord | Australia | |||
| 50 | Darlinghurst | Australia | |||
| 51 | Hobart | Australia | |||
| 52 | Melbourne | Australia | |||
| 53 | Nedlands | Australia | |||
| 54 | Perth | Australia | |||
| 55 | Randwick | Australia | |||
| 56 | South Brisbane | Australia | |||
| 57 | Woolloongabba | Australia | |||
| 58 | Antwerpen | Belgium | |||
| 59 | Brugge | Belgium | |||
| 60 | Brussel | Belgium | |||
| 61 | Gent | Belgium | |||
| 62 | Haine-saint-paul, LA Louviere | Belgium | |||
| 63 | Kortrijk | Belgium | |||
| 64 | Leuven | Belgium | |||
| 65 | Porto Alegre | Brazil | |||
| 66 | Rio de Janeiro | Brazil | |||
| 67 | Sao Paulo | Brazil | |||
| 68 | São Paulo | Brazil | |||
| 69 | Edmonton | Alberta | Canada | ||
| 70 | Vancouver | British Columbia | Canada | ||
| 71 | Halifax | Nova Scotia | Canada | ||
| 72 | Toronto | Ontario | Canada | ||
| 73 | Levis | Quebec | Canada | ||
| 74 | Montreal | Quebec | Canada | ||
| 75 | Montréal | Quebec | Canada | ||
| 76 | Beijing | China | |||
| 77 | Changchun | China | |||
| 78 | Chengdu | China | |||
| 79 | Guangzhou | China | |||
| 80 | Hangzhou | China | |||
| 81 | Harbin | China | |||
| 82 | Jinan | China | |||
| 83 | Nanjing | China | |||
| 84 | Shanghai | China | |||
| 85 | Tianjin | China | |||
| 86 | Brno | Czechia | |||
| 87 | Hradec Kralove | Czechia | |||
| 88 | Ostrava | Czechia | |||
| 89 | Praha 10 | Czechia | |||
| 90 | Praha 2 | Czechia | |||
| 91 | Aarhus N. | Denmark | |||
| 92 | Copenhagen | Denmark | |||
| 93 | Roskilde | Denmark | |||
| 94 | Vejle | Denmark | |||
| 95 | Helsinki | Finland | |||
| 96 | Jyväskylä | Finland | |||
| 97 | Oulu | Finland | |||
| 98 | Turku | Finland | |||
| 99 | Grenoble Cedex 9 | France | |||
| 100 | Limoges | France | |||
| 101 | Paris | France | |||
| 102 | Pessac | France | |||
| 103 | Pierre Benite | France | |||
| 104 | Rouen | France | |||
| 105 | Tours | France | |||
| 106 | Villejuif | France | |||
| 107 | Augsburg | Germany | |||
| 108 | Bamberg | Germany | |||
| 109 | Berlin | Germany | |||
| 110 | Dresden | Germany | |||
| 111 | Essen | Germany | |||
| 112 | Frankfurt | Germany | |||
| 113 | Jena | Germany | |||
| 114 | Muenchen | Germany | |||
| 115 | Münster | Germany | |||
| 116 | Villingen-Schwenningen | Germany | |||
| 117 | Budapest N/a | Hungary | |||
| 118 | Debrecen | Hungary | |||
| 119 | Gyula | Hungary | |||
| 120 | Szombathely | Hungary | |||
| 121 | Veszprém | Hungary | |||
| 122 | Beer-Sheva | Israel | |||
| 123 | Hadera | Israel | |||
| 124 | Haifa | Israel | |||
| 125 | Petah Tikva | Israel | |||
| 126 | Ramat-Gan | Israel | |||
| 127 | Tel Aviv | Israel | |||
| 128 | Fukuoka | Japan | |||
| 129 | Hiroshima | Japan | |||
| 130 | Isehara | Japan | |||
| 131 | Kobe | Japan | |||
| 132 | Kumamoto | Japan | |||
| 133 | Kyoto | Japan | |||
| 134 | Nagano | Japan | |||
| 135 | Nagoya | Japan | |||
| 136 | Narita | Japan | |||
| 137 | Osaka-Sayama | Japan | |||
| 138 | Osaka | Japan | |||
| 139 | Sapporo | Japan | |||
| 140 | Sendai | Japan | |||
| 141 | Suita | Japan | |||
| 142 | Tachikawa | Japan | |||
| 143 | Tokyo | Japan | |||
| 144 | Tsukuba | Japan | |||
| 145 | Busan | Korea, Republic of | |||
| 146 | Goyang-Si | Korea, Republic of | |||
| 147 | Seoul | Korea, Republic of | |||
| 148 | Mexico | Mexico | |||
| 149 | Monterrey | Mexico | |||
| 150 | San Luis Potosi | Mexico | |||
| 151 | Amsterdam Zuidoost | Netherlands | |||
| 152 | Arnhem | Netherlands | |||
| 153 | Dordrecht | Netherlands | |||
| 154 | Groningen | Netherlands | |||
| 155 | Leiden | Netherlands | |||
| 156 | Nieuwegein | Netherlands | |||
| 157 | Rotterdam | Netherlands | |||
| 158 | Oslo | Norway | |||
| 159 | Tromso | Norway | |||
| 160 | Brzozow | Poland | |||
| 161 | Chorzów | Poland | |||
| 162 | Krakow | Poland | |||
| 163 | Lodz | Poland | |||
| 164 | Olsztyn | Poland | |||
| 165 | Poznan | Poland | |||
| 166 | Warszawa | Poland | |||
| 167 | Wroclaw | Poland | |||
| 168 | Ekaterinburg | Russian Federation | |||
| 169 | Moscow | Russian Federation | |||
| 170 | Nizhny Novgorod | Russian Federation | |||
| 171 | Rostov-Na-Donu | Russian Federation | |||
| 172 | Saint-Petersburg, | Russian Federation | |||
| 173 | Sochi | Russian Federation | |||
| 174 | St. Petersburg | Russian Federation | |||
| 175 | Volgograd | Russian Federation | |||
| 176 | Barcelona | Spain | |||
| 177 | Madrid | Spain | |||
| 178 | Salamanca | Spain | |||
| 179 | Sevilla | Spain | |||
| 180 | Linköping | Sweden | |||
| 181 | Luleå | Sweden | |||
| 182 | Lund | Sweden | |||
| 183 | Uppsala | Sweden | |||
| 184 | Taichung | Taiwan | |||
| 185 | Tainan | Taiwan | |||
| 186 | Taoyuan County | Taiwan | |||
| 187 | Adana | Turkey | |||
| 188 | Ankara | Turkey | |||
| 189 | Istanbul | Turkey | |||
| 190 | Izmir | Turkey | |||
| 191 | Kayseri | Turkey | |||
| 192 | Samsun | Turkey | |||
| 193 | Cherkassy | Ukraine | |||
| 194 | Khmelnitskiy | Ukraine | |||
| 195 | Kiev | Ukraine | |||
| 196 | Lviv | Ukraine | |||
| 197 | Makiivka | Ukraine | |||
| 198 | Glasgow | United Kingdom | |||
| 199 | Liverpool | United Kingdom | |||
| 200 | London | United Kingdom | |||
| 201 | Maidstone | United Kingdom | |||
| 202 | Manchester | United Kingdom | |||
| 203 | Nottingham | United Kingdom | |||
| 204 | Oxford | United Kingdom | |||
| 205 | Romford | United Kingdom | |||
| 206 | Southampton | United Kingdom |
Sponsors and Collaborators
- Janssen Research & Development, LLC
- Pharmacyclics LLC.
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01855750
Other Study ID Numbers:
- CR102118
- PCI-32765DBL3001
- U1111-1139-6222
- 2013-000959-40
First Posted:
May 16, 2013
Last Update Posted:
Apr 13, 2020
Last Verified:
Mar 1, 2020
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment Arm B: Ibrutinib+R-CHOP | Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| 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 | 418 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 419 | 419 |
Baseline Characteristics
| Arm/Group Title | Treatment Arm B: Ibrutinib+R-CHOP | Treatment Arm A: Placebo+R-CHOP | Total |
|---|---|---|---|
| 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 Participants | 419 | 419 | 838 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
61.1
(12.57)
|
58.8
(13.57)
|
59.9
(13.12)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
198
47.3%
|
193
46.1%
|
391
46.7%
|
| Male |
221
52.7%
|
226
53.9%
|
447
53.3%
|
| Ethnicity (NIH/OMB) (Count of 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 (Count of Participants) | |||
| White |
237
56.6%
|
250
59.7%
|
487
58.1%
|
| Black or African American |
4
1%
|
4
1%
|
8
1%
|
| 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%
|
| Other |
1
0.2%
|
1
0.2%
|
2
0.2%
|
| Unknown |
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 (Count of 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%
|
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%
|
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%
|
| 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%
|
| Spain |
5
1.2%
|
7
1.7%
|
12
1.4%
|
| Sweden |
0
0%
|
1
0.2%
|
1
0.1%
|
| Taiwan, Province Of China |
8
1.9%
|
9
2.1%
|
17
2%
|
| 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%
|
Outcome Measures
| Title | Event-Free Survival (EFS) - Intent-to-Treat (ITT) Population |
|---|---|
| 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 5.5 years |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 419 | 419 |
| Median (95% Confidence Interval) [Months] |
49.64
|
54.77
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5167 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.922 | |
| Confidence Interval |
(2-Sided) 95% 0.720 to 1.180 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Event-Free Survival (EFS) - Activated B-Cell (ABC) Population |
|---|---|
| Description | 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. |
| Time Frame | Up to approximately 4.5 years |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 285 | 282 |
| Median (95% Confidence Interval) [Months] |
48.56
|
48.16
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7311 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.949 | |
| Confidence Interval |
(2-Sided) 95% 0.704 to 1.279 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-Free Survival (PFS) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 419 | 419 |
| Median (95% Confidence Interval) [Months] |
48.56
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5027 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.917 | |
| Confidence Interval |
(2-Sided) 95% 0.710 to 1.183 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Who Achieved Complete Response (CR) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 419 | 419 |
| Number [Percentage of participants] |
67.3
16.1%
|
68.0
16.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8229 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel (CMH) Chi-square | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.967 | |
| Confidence Interval |
(2-Sided) 95% 0.722 to 1.296 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival |
|---|---|
| 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 5.5 years |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 419 | 419 |
| Median (95% Confidence Interval) [Months] |
NA
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8549 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.030 | |
| Confidence Interval |
(2-Sided) 95% 0.754 to 1.407 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Worsening in the Lymphoma Subscale of Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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). |
| Measure Participants | 419 | 419 |
| Median (95% Confidence Interval) [Months] |
11.7
|
35.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Arm B: Ibrutinib+R-CHOP, Treatment Arm A: Placebo+R-CHOP |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0021 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.358 | |
| Confidence Interval |
(2-Sided) 95% 1.115 to 1.654 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Up to 5.5 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 | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 78/416 (18.8%) | 78/418 (18.7%) | ||
Serious Adverse Events |
||||
| Treatment Arm B: Ibrutinib+R-CHOP | Treatment Arm A: Placebo+R-CHOP | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 221/416 (53.1%) | 143/418 (34.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 15/416 (3.6%) | 5/418 (1.2%) | ||
| Febrile Neutropenia | 78/416 (18.8%) | 44/418 (10.5%) | ||
| Leukopenia | 4/416 (1%) | 2/418 (0.5%) | ||
| Lymphopenia | 1/416 (0.2%) | 0/418 (0%) | ||
| Neutropenia | 17/416 (4.1%) | 13/418 (3.1%) | ||
| Pancytopenia | 0/416 (0%) | 1/418 (0.2%) | ||
| Thrombocytopenia | 9/416 (2.2%) | 1/418 (0.2%) | ||
| Cardiac disorders | ||||
| Acute Coronary Syndrome | 1/416 (0.2%) | 0/418 (0%) | ||
| Acute Myocardial Infarction | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Angina Pectoris | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Arteriosclerosis Coronary Artery | 1/416 (0.2%) | 0/418 (0%) | ||
| Atrial Fibrillation | 13/416 (3.1%) | 2/418 (0.5%) | ||
| Atrial Flutter | 1/416 (0.2%) | 0/418 (0%) | ||
| Cardiac Arrest | 1/416 (0.2%) | 0/418 (0%) | ||
| Cardiac Failure | 2/416 (0.5%) | 5/418 (1.2%) | ||
| Cardiac Failure Acute | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Cardiac Failure Congestive | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Cardiomyopathy | 0/416 (0%) | 1/418 (0.2%) | ||
| Cardiopulmonary Failure | 0/416 (0%) | 1/418 (0.2%) | ||
| Left Ventricular Dysfunction | 0/416 (0%) | 1/418 (0.2%) | ||
| Myocardial Infarction | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Myocardial Ischaemia | 2/416 (0.5%) | 0/418 (0%) | ||
| Sinus Node Dysfunction | 1/416 (0.2%) | 0/418 (0%) | ||
| Supraventricular Tachycardia | 0/416 (0%) | 1/418 (0.2%) | ||
| Tachycardia | 2/416 (0.5%) | 0/418 (0%) | ||
| Ventricular Tachycardia | 1/416 (0.2%) | 0/418 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Congenital Neuropathy | 0/416 (0%) | 1/418 (0.2%) | ||
| Pyloric Stenosis | 1/416 (0.2%) | 0/418 (0%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 1/416 (0.2%) | 0/418 (0%) | ||
| Eye disorders | ||||
| Eye Haemorrhage | 1/416 (0.2%) | 0/418 (0%) | ||
| Glaucoma | 1/416 (0.2%) | 0/418 (0%) | ||
| Retinal Detachment | 0/416 (0%) | 1/418 (0.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 2/416 (0.5%) | 2/418 (0.5%) | ||
| Colitis | 3/416 (0.7%) | 0/418 (0%) | ||
| Constipation | 1/416 (0.2%) | 0/418 (0%) | ||
| Diarrhoea | 15/416 (3.6%) | 4/418 (1%) | ||
| Diverticular Perforation | 1/416 (0.2%) | 0/418 (0%) | ||
| Duodenal Ulcer Haemorrhage | 1/416 (0.2%) | 0/418 (0%) | ||
| Dyspepsia | 0/416 (0%) | 1/418 (0.2%) | ||
| Enteritis | 1/416 (0.2%) | 0/418 (0%) | ||
| Gastric Haemorrhage | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Gastric Perforation | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Gastrointestinal Haemorrhage | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Gastrooesophageal Reflux Disease | 0/416 (0%) | 1/418 (0.2%) | ||
| Ileus | 1/416 (0.2%) | 2/418 (0.5%) | ||
| Intestinal Obstruction | 2/416 (0.5%) | 0/418 (0%) | ||
| Lower Gastrointestinal Haemorrhage | 1/416 (0.2%) | 0/418 (0%) | ||
| Mechanical Ileus | 0/416 (0%) | 1/418 (0.2%) | ||
| Nausea | 6/416 (1.4%) | 3/418 (0.7%) | ||
| Neutropenic Colitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Obstruction Gastric | 0/416 (0%) | 1/418 (0.2%) | ||
| Oesophagitis | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Pancreatitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Rectal Haemorrhage | 1/416 (0.2%) | 0/418 (0%) | ||
| Small Intestinal Obstruction | 0/416 (0%) | 1/418 (0.2%) | ||
| Small Intestinal Perforation | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Stomatitis | 2/416 (0.5%) | 0/418 (0%) | ||
| Vomiting | 8/416 (1.9%) | 2/418 (0.5%) | ||
| General disorders | ||||
| Asthenia | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Chest Pain | 1/416 (0.2%) | 0/418 (0%) | ||
| Device Related Thrombosis | 0/416 (0%) | 1/418 (0.2%) | ||
| Drowning | 0/416 (0%) | 1/418 (0.2%) | ||
| Fatigue | 5/416 (1.2%) | 1/418 (0.2%) | ||
| General Physical Health Deterioration | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Injection Site Extravasation | 1/416 (0.2%) | 0/418 (0%) | ||
| Malaise | 1/416 (0.2%) | 0/418 (0%) | ||
| Mucosal Inflammation | 3/416 (0.7%) | 0/418 (0%) | ||
| Multiple Organ Dysfunction Syndrome | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Non-Cardiac Chest Pain | 0/416 (0%) | 1/418 (0.2%) | ||
| Oedema Peripheral | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Pain | 1/416 (0.2%) | 0/418 (0%) | ||
| Pyrexia | 12/416 (2.9%) | 11/418 (2.6%) | ||
| Sudden Death | 2/416 (0.5%) | 2/418 (0.5%) | ||
| Hepatobiliary disorders | ||||
| Cholangitis | 0/416 (0%) | 1/418 (0.2%) | ||
| Cholecystitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Hepatic Failure | 2/416 (0.5%) | 0/418 (0%) | ||
| Hepatic Function Abnormal | 1/416 (0.2%) | 2/418 (0.5%) | ||
| Infections and infestations | ||||
| Arteritis Infective | 1/416 (0.2%) | 0/418 (0%) | ||
| Aspergillus Infection | 2/416 (0.5%) | 0/418 (0%) | ||
| Atypical Pneumonia | 1/416 (0.2%) | 0/418 (0%) | ||
| Bacteraemia | 1/416 (0.2%) | 0/418 (0%) | ||
| Brain Abscess | 1/416 (0.2%) | 0/418 (0%) | ||
| Bronchitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Bronchopulmonary Aspergillosis | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Cellulitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Cerebral Aspergillosis | 1/416 (0.2%) | 0/418 (0%) | ||
| Clostridial Infection | 2/416 (0.5%) | 0/418 (0%) | ||
| Cryptococcal Fungaemia | 1/416 (0.2%) | 0/418 (0%) | ||
| Cytomegalovirus Gastrointestinal Infection | 0/416 (0%) | 1/418 (0.2%) | ||
| Device Related Infection | 4/416 (1%) | 1/418 (0.2%) | ||
| Enterococcal Sepsis | 1/416 (0.2%) | 0/418 (0%) | ||
| Erysipelas | 0/416 (0%) | 1/418 (0.2%) | ||
| Gastroenteritis | 1/416 (0.2%) | 0/418 (0%) | ||
| Gastroenteritis Bacterial | 0/416 (0%) | 1/418 (0.2%) | ||
| Haemophilus Infection | 0/416 (0%) | 1/418 (0.2%) | ||
| Hepatitis B | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Hepatitis B Reactivation | 0/416 (0%) | 1/418 (0.2%) | ||
| Herpes Zoster | 2/416 (0.5%) | 3/418 (0.7%) | ||
| Incision Site Infection | 0/416 (0%) | 1/418 (0.2%) | ||
| Infection | 3/416 (0.7%) | 2/418 (0.5%) | ||
| Klebsiella Sepsis | 0/416 (0%) | 1/418 (0.2%) | ||
| Lower Respiratory Tract Infection | 1/416 (0.2%) | 0/418 (0%) | ||
| Lower Respiratory Tract Infection Fungal | 1/416 (0.2%) | 0/418 (0%) | ||
| Lung Abscess | 1/416 (0.2%) | 0/418 (0%) | ||
| Lung Infection | 14/416 (3.4%) | 7/418 (1.7%) | ||
| Lymph Gland Infection | 0/416 (0%) | 1/418 (0.2%) | ||
| Mucosal Infection | 1/416 (0.2%) | 0/418 (0%) | ||
| Neutropenic Infection | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Neutropenic Sepsis | 1/416 (0.2%) | 2/418 (0.5%) | ||
| Peritonitis | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Pharyngitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Pneumocystis Jirovecii Pneumonia | 3/416 (0.7%) | 0/418 (0%) | ||
| Pneumonia | 28/416 (6.7%) | 14/418 (3.3%) | ||
| Pneumonia Cryptococcal | 1/416 (0.2%) | 0/418 (0%) | ||
| Pneumonia Cytomegaloviral | 1/416 (0.2%) | 0/418 (0%) | ||
| Pneumonia Klebsiella | 2/416 (0.5%) | 0/418 (0%) | ||
| Pneumonia Respiratory Syncytial Viral | 0/416 (0%) | 1/418 (0.2%) | ||
| Pseudomembranous Colitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Pulmonary Mycosis | 1/416 (0.2%) | 0/418 (0%) | ||
| Respiratory Syncytial Virus Infection | 1/416 (0.2%) | 0/418 (0%) | ||
| Respiratory Tract Infection | 1/416 (0.2%) | 0/418 (0%) | ||
| Respiratory Tract Infection Bacterial | 1/416 (0.2%) | 0/418 (0%) | ||
| Respiratory Tract Infection Fungal | 1/416 (0.2%) | 0/418 (0%) | ||
| Sepsis | 7/416 (1.7%) | 3/418 (0.7%) | ||
| Septic Shock | 5/416 (1.2%) | 1/418 (0.2%) | ||
| Sialoadenitis | 0/416 (0%) | 1/418 (0.2%) | ||
| Sinusitis | 0/416 (0%) | 2/418 (0.5%) | ||
| Upper Respiratory Tract Infection | 3/416 (0.7%) | 1/418 (0.2%) | ||
| Urinary Tract Infection | 5/416 (1.2%) | 3/418 (0.7%) | ||
| Urosepsis | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Viral Infection | 2/416 (0.5%) | 0/418 (0%) | ||
| Viral Upper Respiratory Tract Infection | 1/416 (0.2%) | 0/418 (0%) | ||
| Wound Infection | 0/416 (0%) | 1/418 (0.2%) | ||
| Injury, poisoning and procedural complications | ||||
| Compression Fracture | 1/416 (0.2%) | 0/418 (0%) | ||
| Femoral Neck Fracture | 0/416 (0%) | 1/418 (0.2%) | ||
| Fibula Fracture | 1/416 (0.2%) | 0/418 (0%) | ||
| Hip Fracture | 0/416 (0%) | 2/418 (0.5%) | ||
| Humerus Fracture | 0/416 (0%) | 1/418 (0.2%) | ||
| Infusion Related Reaction | 1/416 (0.2%) | 0/418 (0%) | ||
| Lumbar Vertebral Fracture | 1/416 (0.2%) | 0/418 (0%) | ||
| Postoperative Thrombosis | 1/416 (0.2%) | 0/418 (0%) | ||
| Pubis Fracture | 1/416 (0.2%) | 0/418 (0%) | ||
| Skull Fractured Base | 1/416 (0.2%) | 0/418 (0%) | ||
| Spinal Compression Fracture | 1/416 (0.2%) | 0/418 (0%) | ||
| Subdural Haematoma | 0/416 (0%) | 3/418 (0.7%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 0/416 (0%) | 1/418 (0.2%) | ||
| C-Reactive Protein Increased | 0/416 (0%) | 1/418 (0.2%) | ||
| Neutrophil Count Decreased | 5/416 (1.2%) | 2/418 (0.5%) | ||
| Platelet Count Decreased | 2/416 (0.5%) | 0/418 (0%) | ||
| Weight Decreased | 1/416 (0.2%) | 0/418 (0%) | ||
| White Blood Cell Count Decreased | 3/416 (0.7%) | 0/418 (0%) | ||
| White Blood Cell Count Increased | 1/416 (0.2%) | 0/418 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 0/416 (0%) | 2/418 (0.5%) | ||
| Dehydration | 8/416 (1.9%) | 2/418 (0.5%) | ||
| Diabetes Mellitus | 0/416 (0%) | 1/418 (0.2%) | ||
| Fluid Overload | 1/416 (0.2%) | 0/418 (0%) | ||
| Hyperglycaemia | 0/416 (0%) | 1/418 (0.2%) | ||
| Hypokalaemia | 4/416 (1%) | 0/418 (0%) | ||
| Hyponatraemia | 3/416 (0.7%) | 1/418 (0.2%) | ||
| Hypophagia | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Hypoproteinaemia | 1/416 (0.2%) | 0/418 (0%) | ||
| Ketoacidosis | 0/416 (0%) | 1/418 (0.2%) | ||
| Tumour Lysis Syndrome | 1/416 (0.2%) | 0/418 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/416 (0.2%) | 0/418 (0%) | ||
| Back Pain | 1/416 (0.2%) | 0/418 (0%) | ||
| Chondrocalcinosis Pyrophosphate | 1/416 (0.2%) | 0/418 (0%) | ||
| Flank Pain | 0/416 (0%) | 1/418 (0.2%) | ||
| Muscular Weakness | 2/416 (0.5%) | 0/418 (0%) | ||
| Myalgia | 1/416 (0.2%) | 0/418 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Angioimmunoblastic T-Cell Lymphoma | 0/416 (0%) | 1/418 (0.2%) | ||
| Basal Cell Carcinoma | 1/416 (0.2%) | 0/418 (0%) | ||
| Colorectal Adenocarcinoma | 0/416 (0%) | 1/418 (0.2%) | ||
| Laryngeal Cancer Metastatic | 1/416 (0.2%) | 0/418 (0%) | ||
| Malignant Melanoma | 1/416 (0.2%) | 0/418 (0%) | ||
| Squamous Cell Carcinoma of Skin | 1/416 (0.2%) | 0/418 (0%) | ||
| Nervous system disorders | ||||
| Altered State of Consciousness | 1/416 (0.2%) | 0/418 (0%) | ||
| Central Nervous System Inflammation | 0/416 (0%) | 1/418 (0.2%) | ||
| Cerebral Haemorrhage | 1/416 (0.2%) | 0/418 (0%) | ||
| Cerebral Infarction | 0/416 (0%) | 1/418 (0.2%) | ||
| Cerebrospinal Fluid Leakage | 0/416 (0%) | 1/418 (0.2%) | ||
| Cerebrovascular Disorder | 1/416 (0.2%) | 0/418 (0%) | ||
| Dizziness Postural | 1/416 (0.2%) | 0/418 (0%) | ||
| Epilepsy | 0/416 (0%) | 1/418 (0.2%) | ||
| Febrile Convulsion | 1/416 (0.2%) | 0/418 (0%) | ||
| Haemorrhage Intracranial | 2/416 (0.5%) | 0/418 (0%) | ||
| Hemiparesis | 0/416 (0%) | 1/418 (0.2%) | ||
| Intracranial Hypotension | 0/416 (0%) | 1/418 (0.2%) | ||
| Nerve Compression | 0/416 (0%) | 1/418 (0.2%) | ||
| Polyneuropathy | 1/416 (0.2%) | 0/418 (0%) | ||
| Sciatica | 1/416 (0.2%) | 0/418 (0%) | ||
| Seizure | 1/416 (0.2%) | 0/418 (0%) | ||
| Syncope | 5/416 (1.2%) | 1/418 (0.2%) | ||
| Psychiatric disorders | ||||
| Bipolar I Disorder | 0/416 (0%) | 1/418 (0.2%) | ||
| Confusional State | 0/416 (0%) | 1/418 (0.2%) | ||
| Suicidal Ideation | 1/416 (0.2%) | 0/418 (0%) | ||
| Renal and urinary disorders | ||||
| Acute Kidney Injury | 4/416 (1%) | 1/418 (0.2%) | ||
| Cystitis Haemorrhagic | 1/416 (0.2%) | 0/418 (0%) | ||
| Dysuria | 1/416 (0.2%) | 0/418 (0%) | ||
| Pollakiuria | 1/416 (0.2%) | 0/418 (0%) | ||
| Renal Failure | 1/416 (0.2%) | 2/418 (0.5%) | ||
| Urinary Retention | 1/416 (0.2%) | 0/418 (0%) | ||
| Reproductive system and breast disorders | ||||
| Vaginal Fistula | 1/416 (0.2%) | 0/418 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Respiratory Failure | 0/416 (0%) | 1/418 (0.2%) | ||
| Alveolitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Atelectasis | 0/416 (0%) | 1/418 (0.2%) | ||
| Diffuse Alveolar Damage | 1/416 (0.2%) | 0/418 (0%) | ||
| Dyspnoea | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Hypoxia | 1/416 (0.2%) | 0/418 (0%) | ||
| Interstitial Lung Disease | 7/416 (1.7%) | 4/418 (1%) | ||
| Obliterative Bronchiolitis | 0/416 (0%) | 1/418 (0.2%) | ||
| Pharyngeal Haemorrhage | 0/416 (0%) | 1/418 (0.2%) | ||
| Pleural Effusion | 1/416 (0.2%) | 1/418 (0.2%) | ||
| Pneumonia Aspiration | 1/416 (0.2%) | 0/418 (0%) | ||
| Pneumonitis | 6/416 (1.4%) | 3/418 (0.7%) | ||
| Pulmonary Embolism | 1/416 (0.2%) | 3/418 (0.7%) | ||
| Pulmonary Mass | 1/416 (0.2%) | 0/418 (0%) | ||
| Respiratory Failure | 2/416 (0.5%) | 1/418 (0.2%) | ||
| Sinus Polyp | 1/416 (0.2%) | 0/418 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis Allergic | 1/416 (0.2%) | 0/418 (0%) | ||
| Vascular disorders | ||||
| Aortic Aneurysm | 1/416 (0.2%) | 0/418 (0%) | ||
| Arteriosclerosis | 1/416 (0.2%) | 0/418 (0%) | ||
| Deep Vein Thrombosis | 1/416 (0.2%) | 2/418 (0.5%) | ||
| Embolism | 0/416 (0%) | 1/418 (0.2%) | ||
| Hypotension | 6/416 (1.4%) | 1/418 (0.2%) | ||
| Shock Haemorrhagic | 1/416 (0.2%) | 0/418 (0%) | ||
| Thrombophlebitis | 1/416 (0.2%) | 0/418 (0%) | ||
| Vena Cava Thrombosis | 0/416 (0%) | 1/418 (0.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Treatment Arm B: Ibrutinib+R-CHOP | Treatment Arm A: Placebo+R-CHOP | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 411/416 (98.8%) | 411/418 (98.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 173/416 (41.6%) | 116/418 (27.8%) | ||
| Febrile Neutropenia | 41/416 (9.9%) | 22/418 (5.3%) | ||
| Leukopenia | 70/416 (16.8%) | 74/418 (17.7%) | ||
| Lymphopenia | 23/416 (5.5%) | 36/418 (8.6%) | ||
| Neutropenia | 213/416 (51.2%) | 248/418 (59.3%) | ||
| Thrombocytopenia | 102/416 (24.5%) | 53/418 (12.7%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Pain | 37/416 (8.9%) | 34/418 (8.1%) | ||
| Abdominal Pain Upper | 28/416 (6.7%) | 34/418 (8.1%) | ||
| Constipation | 111/416 (26.7%) | 110/418 (26.3%) | ||
| Diarrhoea | 149/416 (35.8%) | 81/418 (19.4%) | ||
| Dry Mouth | 22/416 (5.3%) | 17/418 (4.1%) | ||
| Dyspepsia | 26/416 (6.3%) | 22/418 (5.3%) | ||
| Mouth Ulceration | 32/416 (7.7%) | 20/418 (4.8%) | ||
| Nausea | 170/416 (40.9%) | 135/418 (32.3%) | ||
| Stomatitis | 64/416 (15.4%) | 47/418 (11.2%) | ||
| Vomiting | 91/416 (21.9%) | 59/418 (14.1%) | ||
| General disorders | ||||
| Asthenia | 28/416 (6.7%) | 16/418 (3.8%) | ||
| Fatigue | 138/416 (33.2%) | 102/418 (24.4%) | ||
| Malaise | 25/416 (6%) | 21/418 (5%) | ||
| Mucosal Inflammation | 34/416 (8.2%) | 23/418 (5.5%) | ||
| Oedema Peripheral | 46/416 (11.1%) | 29/418 (6.9%) | ||
| Pyrexia | 83/416 (20%) | 68/418 (16.3%) | ||
| Infections and infestations | ||||
| Pneumonia | 22/416 (5.3%) | 9/418 (2.2%) | ||
| Upper Respiratory Tract Infection | 35/416 (8.4%) | 29/418 (6.9%) | ||
| Urinary Tract Infection | 24/416 (5.8%) | 15/418 (3.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Infusion Related Reaction | 23/416 (5.5%) | 26/418 (6.2%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 25/416 (6%) | 24/418 (5.7%) | ||
| Lymphocyte Count Decreased | 44/416 (10.6%) | 42/418 (10%) | ||
| Neutrophil Count Decreased | 99/416 (23.8%) | 81/418 (19.4%) | ||
| Platelet Count Decreased | 83/416 (20%) | 38/418 (9.1%) | ||
| Weight Decreased | 36/416 (8.7%) | 18/418 (4.3%) | ||
| White Blood Cell Count Decreased | 107/416 (25.7%) | 104/418 (24.9%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 64/416 (15.4%) | 51/418 (12.2%) | ||
| Hypoalbuminaemia | 24/416 (5.8%) | 9/418 (2.2%) | ||
| Hypokalaemia | 75/416 (18%) | 23/418 (5.5%) | ||
| Hypomagnesaemia | 22/416 (5.3%) | 7/418 (1.7%) | ||
| Hyponatraemia | 28/416 (6.7%) | 11/418 (2.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 34/416 (8.2%) | 40/418 (9.6%) | ||
| Bone Pain | 17/416 (4.1%) | 21/418 (5%) | ||
| Muscle Spasms | 30/416 (7.2%) | 14/418 (3.3%) | ||
| Myalgia | 18/416 (4.3%) | 24/418 (5.7%) | ||
| Nervous system disorders | ||||
| Dysgeusia | 26/416 (6.3%) | 19/418 (4.5%) | ||
| Headache | 29/416 (7%) | 43/418 (10.3%) | ||
| Hypoaesthesia | 28/416 (6.7%) | 22/418 (5.3%) | ||
| Neuropathy Peripheral | 65/416 (15.6%) | 35/418 (8.4%) | ||
| Paraesthesia | 28/416 (6.7%) | 16/418 (3.8%) | ||
| Peripheral Sensory Neuropathy | 77/416 (18.5%) | 63/418 (15.1%) | ||
| Psychiatric disorders | ||||
| Insomnia | 39/416 (9.4%) | 43/418 (10.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 55/416 (13.2%) | 47/418 (11.2%) | ||
| Dyspnoea | 30/416 (7.2%) | 25/418 (6%) | ||
| Oropharyngeal Pain | 32/416 (7.7%) | 25/418 (6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 69/416 (16.6%) | 106/418 (25.4%) | ||
| Pruritus | 11/416 (2.6%) | 21/418 (5%) | ||
| Rash | 22/416 (5.3%) | 21/418 (5%) | ||
| Vascular disorders | ||||
| Hypertension | 23/416 (5.5%) | 18/418 (4.3%) | ||
| Hypotension | 23/416 (5.5%) | 10/418 (2.4%) | ||
Limitations/Caveats
Sponsor decided to stop the study as all participants had concluded study treatment and outcomes were not expected to change and study was considered as completed.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
| Name/Title | Medical Officer |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01855750
Other Study ID Numbers:
- CR102118
- PCI-32765DBL3001
- U1111-1139-6222
- 2013-000959-40
First Posted:
May 16, 2013
Last Update Posted:
Apr 13, 2020
Last Verified:
Mar 1, 2020