A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Terminated

CT.gov ID

NCT01287741

Collaborator

Fondazione Italiana Linfomi ONLUS (Other)

1,418

Enrollment

235

Locations

Arms

78.2

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label, randomized, parallel group study will evaluate the efficacy and safety of obinutuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone or prednisone (CHOP) chemotherapy versus rituximab (MabThera/Rituxan) with CHOP in previously untreated participants with cluster of differentiation 20 (CD20)-positive diffuse large B-cell lymphoma (DLBCL). Participants will be randomized to receive either obinutuzumab 1000 milligrams (mg) intravenously (IV) every 21 days or rituximab 375 milligrams per square meter (mg/m^2) IV every 21 days for 8 cycles, in addition to 6-8 cycles of CHOP chemotherapy IV every 21 days. Participants randomized to the obinutuzumab arm will receive an additional two doses on Days 8 and 15 of Cycle 1. Anticipated time on study treatment is 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: Rituximab Drug: Obinutuzumab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1418 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III, Multicenter, Open-Label Randomized Trial Comparing the Efficacy of GA101 (RO5072759) in Combination With CHOP (G-CHOP) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients With CD20-Positive Diffuse Large B-Cell Lymphoma (DLBCL)

Actual Study Start Date :

Jul 26, 2011

Actual Primary Completion Date :

Apr 29, 2016

Actual Study Completion Date :

Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rituximab+Chemotherapy Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Drug: Rituximab Rituximab at a dose of 375 mg/m^2, administered by intravenous (IV) infusion on Day 1 of each 21-day cycle for 8 cycles. Other Names: MabThera, Rituxan Drug: Cyclophosphamide Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle. Drug: Doxorubicin Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle. Drug: Vincristine Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle. Drug: Prednisone Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle.
Experimental: Obinutuzumab+Chemotherapy Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Drug: Obinutuzumab Obinutuzumab 1000 mg IV infusion, administered on Day 1 of each 21-day cycle for 8 cycles. During Cycle 1, obinutuzumab was also infused on Days 8 and 15. Other Names: GA101, RO5072759 Drug: Cyclophosphamide Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle. Drug: Doxorubicin Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle. Drug: Vincristine Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle. Drug: Prednisone Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle.

Arm

Intervention/Treatment

Active Comparator: Rituximab+Chemotherapy

Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.

Drug: Rituximab

Rituximab at a dose of 375 mg/m^2, administered by intravenous (IV) infusion on Day 1 of each 21-day cycle for 8 cycles.

Other Names:

MabThera, Rituxan

Drug: Cyclophosphamide

Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle.

Drug: Doxorubicin

Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle.

Drug: Vincristine

Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle.

Drug: Prednisone

Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle.

Experimental: Obinutuzumab+Chemotherapy

Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.

Drug: Obinutuzumab

Obinutuzumab 1000 mg IV infusion, administered on Day 1 of each 21-day cycle for 8 cycles. During Cycle 1, obinutuzumab was also infused on Days 8 and 15.

Other Names:

GA101, RO5072759

Drug: Cyclophosphamide

Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle.

Drug: Doxorubicin

Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle.

Drug: Vincristine

Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle.

Drug: Prednisone

Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle.

Outcome Measures

Primary Outcome Measures

Median Time to Progression-Free Survival (PFS), Investigator-Assessed [Baseline up to approximately 6.5 years (up to 31 January 2018)]
Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]). Progression-free survival was defined as the time from randomization until the first documented day of disease progression or relapse, using a modified version of the Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).

Secondary Outcome Measures

Median Time to Progression-Free Survival (PFS), Independent Review Committee (IRC)-Assessed [Baseline up to approximately 4 years and 9 months (up to 29 April 2016)]
Kaplan Meier estimate of median PFS was defined as time at which half of participants have progressed (progressive disease [PD]). Progression-free survival was defined as time from randomization until first documented day of disease progression or relapse, using a modified version of Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on basis of IRC assessments. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 cm or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT or MRI. This outcome measure used data from primary analysis which included all 1418 participants.
Median Time to Overall Survival (OS) [Baseline up to approximately 6.5 years (up to 31 January 2018)]
Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death. Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause.
Overall Response Rate (ORR), Investigator-Assessed [Baseline up to approximately 6.5 years (up to 31 January 2018)]
Overall response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.
Overall Response Rate (ORR), IRC-Assessed [Baseline up to approximately 4 years and 9 months (up to 29 April 2016)]
Overall response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites. This outcome measure used data from primary analysis which included all 1418 participants.
Complete Response (CR) at the End of Treatment, Investigator-Assessed [Baseline up to approximately 6.5 years (up to 31 January 2018)]
Percentage of participants with complete response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease.
Complete Response (CR) at the End of Treatment, IRC-Assessed [Baseline up to approximately 4 years and 9 months (up to 29 April 2016)]
Percentage of participants with complete response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease. This outcome measure used data from primary analysis which included all 1418 participants.
Median Time to Event-Free Survival (EFS), Investigator-Assessed [Baseline up to death or disease progression, or initiation of new anti-lymphoma treatment (NALT), whichever occurred first, approximately 6.5 years (up to 31 January 2018)]
Kaplan Meier estimate of median EFS is the time at which half of the participants have progressed. Event-free survival was defined as the time from the date of randomization until the date of disease progression, relapse, initiation of a new non-protocol-specified anti-lymphoma treatment, or death from any cause on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.
Median Time to Disease-Free Survival (DFS), Investigator-Assessed [Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018)]
Kaplan Meier estimate of median DFS was defined as time at which half of participants have disease progression/relapse or death from any cause. Disease-free survival was defined as time from date of the first occurrence of a documented CR to date of disease progression/relapse or death from any cause on basis of investigator assessments with use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.
Duration of Response (DOR), Investigator-Assessed [Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018)]
DOR: time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with CT/MRI. CR: disappearance of all target lesions. PR: >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodule regression >/= 50%. Progression/relapse: at least 50% increase in nodal lesions or >/=50% increase in any node > 1 cm or >/= 50% increase in other target lesions (e.g., splenic or hepatic nodules) and/or any new bone marrow involvement and/or any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. A participant in the Rituximab+CHOP arm with the longest follow-up, 53 months, had an event. The criterion for median was the minimum time when survival went below 50%.
Time to Next Anti-Lymphoma Treatment (TTNALT) [Baseline up to start of next anti-lymphoma treatment or death due to any cause, whichever occurred first, approximately 6.5 years (31 January 2018)]
Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause.
Percentage of Participants With Adverse Events (AEs) [Baseline up to approximately 6.5 years (up to 31 January 2018)]
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [Pre-dose (Hour 0) on Cycle (C) 4 Day (D) 1, at end of treatment/early termination (up to Month 6), every 6 months thereafter for 30 months (cycle length = 21 days)]
The presence of HAHAs to obinutuzumab was assessed in the first 100 randomized participants.
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale Score [Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to approximately 6.5 years, (cycle length = 21 days)]
The FACT-Lym subscale was developed to assess health-related quality of life in participants with non-Hodgkin lymphoma. The score range is 0-60, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement.
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores [Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to data cut-off, up to approximately 6.5 years, (cycle length = 21 days)]
The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
Serum Concentrations of Obinutuzumab in Japanese Participants With Diffuse Large B-Cell Lymphoma (DLBCL) [C1: D1 post-infusion and 20-28 and 66-80 hours after end of infusion, D8 and D15 pre-and post-infusion; C2: D1 pre- and post-infusion; C4: D1 pre- and post-infusion; C6: D1 pre- and post-infusion; C8: D1 pre- and post-infusion (cycle length = 21 days)]
Serum samples for assessment of obinutuzumab serum concentrations were collected only from a subset of Japanese participants following administration of 1000 mg obinutuzumab.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Previously untreated CD20-positive DLBCL
At least 1 bi-dimensionally measurable lesion (greater than [>]1.5 centimeters [cm] in its largest dimension on the computed tomography [CT] scan)
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Adequate hematological function
Low-intermediate, high-intermediate or high-risk International Prognostic Index (IPI) score (low-risk IPI score: IPI 1 irrespective of bulky disease or IPI 0 with bulky disease, defined as one lesion greater than equal to (>/=) 7.5 cm)
Left ventricular ejection fraction (LVEF) >/=50 percent (%) on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram

Exclusion Criteria:

History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products or to any component of CHOP or obinutuzumab
Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
Participants with transformed lymphoma and participants with follicular lymphoma IIIB
Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
Prior treatment with cytotoxic drugs or rituximab for another condition (for example, rheumatoid arthritis) or prior use of an anti-CD20 antibody
Prior use of any monoclonal antibody within 3 months of the start of Cycle 1
Corticosteroid use of >30 milligrams per day (mg/day) of prednisone or equivalent, for purposes other than lymphoma symptom control
Primary central nervous system (CNS) lymphoma and secondary CNS involvement by lymphoma, mantle-cell lymphoma (MCL), or histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, plasmablastic lymphoma, and primary cutaneous DLBCL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	Ironwood Cancer TX & Rsch Ctrs	Chandler	Arizona	United States	85224
3	Arizona Oncology	Tucson	Arizona	United States	85704
4	California Cancer Associates for Research & Excellence, Inc.	Encinitas	California	United States	92008
5	cCare	Encinitas	California	United States	92024
6	UCLA - School of Medicine; Division of Hematology/Oncology	Los Angeles	California	United States	90095-6984
7	Rocky Mountain Cancer Center - Aurora	Aurora	Colorado	United States	80012
8	Florida Cancer Specialists; Department of Oncology	Fort Myers	Florida	United States	33901-8101
9	Florida Cancer Specialists; Saint Petersburg	Saint Petersburg	Florida	United States	33719
10	Central Georgia Cancer Care PC	Macon	Georgia	United States	31201
11	Illinois Cancer Care, P.C. - Galesburg	Galesburg	Illinois	United States	61401
12	Joliet Oncology-Hematology; Associates, Ltd.	Joliet	Illinois	United States	60435
13	Cancer Care & Hematology; Specialists of Chicagoland	Niles	Illinois	United States	60714
14	Carle Cancer Center	Urbana	Illinois	United States	61801
15	Mercy Oncology / Hematology Center; Oncology	Portland	Maine	United States	04102
16	Park Nicollet Clin-Cancer Ctr	Saint Louis Park	Minnesota	United States	55426
17	Minnesota Oncology Hematology Woodbury	Woodbury	Minnesota	United States	55125
18	New York Oncology Hematology, P.C.	Albany	New York	United States	12206
19	Mecklenburg Medical Group Charlotte	Charlotte	North Carolina	United States	28204
20	Forsyth Regional Cancer Center; Piedmont Hematology/Oncology Associates	Winston-Salem	North Carolina	United States	27103
21	Signal Point Clinical; Research Center, LLC	Middletown	Ohio	United States	45042
22	Cleveland CL N Coast Cancer Cr	Sandusky	Ohio	United States	44870
23	Willamette Valley Cancer Insitute and Research Center	Springfield	Oregon	United States	97477
24	Medical University of SC (MUSC)	Charleston	South Carolina	United States	29425
25	South Carolina Oncology Associates - SCRI	Columbia	South Carolina	United States	29210
26	Chattanooga Oncology and Hematology Associates, PC	Chattanooga	Tennessee	United States	37404
27	Tennessee Onc., PLLC - SCRI	Nashville	Tennessee	United States	37203
28	Texas Oncology, Pa - Amarillo	Amarillo	Texas	United States	79106
29	Texas Oncology-Fort Worth 12th Ave	Fort Worth	Texas	United States	76104
30	MD Anderson Cancer Center Department of Lymphoma & Myeloma	Houston	Texas	United States	77030
31	Cancer Care Centers of South Texas-HOAST - San Antonio	New Braunfels	Texas	United States	78130
32	Virginia Cancer Institute	Richmond	Virginia	United States	23226
33	Blue Ridge Cancer Care	Roanoke	Virginia	United States	24014
34	Virginia Cancer Specialists - Winchester	Winchester	Virginia	United States	22601
35	Northwest Medical Specialties	Tacoma	Washington	United States	98405
36	Wenatchee Valley Hospital & Clinics	Wenatchee	Washington	United States	98801
37	Instituto Damic	Cordoba		Argentina	X5003DCE
38	Sanatorio Britanico: Hematologia	Rosario		Argentina	2000
39	Sanatorio Parque de Rosario	Rosario		Argentina	S2000DSV
40	Cairns Base Hospital; Cancer Care Centre	Cairns	Queensland	Australia	4870
41	Frankston Hospital; Oncology/Haematology	Frankston	Victoria	Australia	3199
42	Monash Medical Centre; Haematology	Melbourne	Victoria	Australia	3168
43	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
44	Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie	Innsbruck		Austria	6020
45	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg		Austria	5020
46	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie	Wien		Austria	1090
47	Hospital Mae de Deus	Porto Alegre	RS	Brazil	90470-340
48	Hospital Sao Lucas - PUCRS	Porto Alegre	RS	Brazil	90610-000
49	Centro de Pesquisas Oncologicas - CEPON	Florianopolis	SC	Brazil	88034-000
50	Instituto de Ensino e Pesquisa Sao Lucas - IEP	Sao Paulo	SP	Brazil	01236-030
51	Hospital Santa Marcelina;Oncologia	Sao Paulo	SP	Brazil	08270-070
52	Tom Baker Cancer Centre; Dept of Medicine	Calgary	Alberta	Canada	T2N 4N2
53	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
54	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
55	Queen Elizabeth II Health Sciences Centre; Oncology	Halifax	Nova Scotia	Canada	B3H 2Y9
56	Ottawa General Hospital	Ottawa	Ontario	Canada	K1H 8L6
57	North York General Hospital	Toronto	Ontario	Canada	M2J 1V1
58	Humber River Hospital	Toronto	Ontario	Canada	M3M 0B2
59	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario	Canada	M5G 2M9
60	Hopital Maisonneuve- Rosemont; Oncology	Montreal	Quebec	Canada	H1T 2M4
61	Chum Hopital Notre Dame; Centre D'Oncologie	Montreal	Quebec	Canada	H2L 4M1
62	Mcgill University - Royal Victoria Hospital; Oncology	Montreal	Quebec	Canada	H3A 1A1
63	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec	Canada	H3T 1E2
64	Hopital de L'Enfant-Jesus; Hematology	Quebec City	Quebec	Canada	G1J 1Z4
65	Centre de sante et de services sociaux Rimouski Neigette	Rimouski	Quebec	Canada	G5L 5T1
66	Saskatoon Cancer Centre; Uni of Saskatoon Campus	Saskatoon	Saskatchewan	Canada	S7N 4H4
67	Cancer Hospital Chinese Academy of Medical Sciences.	Beijing		China	100021
68	Peking University First Hospital	Beijing		China	100034
69	The Affiliated Hospital of Military Medical Sciences(The 307th Hospital of Chinese PLA)	Beijing		China	100071
70	Beijing Cancer Hospital	Beijing		China	100142
71	Beijing Hospital of Ministry of Health; Hematology	Beijing		China	100730
72	General Hospital of Chinese PLA; Department of Hematology	Beijing		China	100853
73	the First Hospital of Jilin University	Changchun		China	130021
74	Hu Nan Provincial Cancer Hospital	Changsha		China	410006
75	Fujian Medical University Union Hospital	Fujian		China	350001
76	Fujian Cancer Hospital	Fuzhou		China	350014
77	Sun Yet-sen University Cancer Center	Guangzhou		China	510060
78	Guangdong General Hospital	Guangzhou		China	510080
79	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou		China	310003
80	Harbin Medical University Cancer Hospital	Harbin		China	150081
81	The Second Affiliated Hospital to Nanchang University	Nanchang		China	330006
82	Jiangsu Cancer Hospital	Nanjing		China	210009
83	Jiangsu Province Hospital	Nanjing		China	210036
84	The First Affiliate Hospital of Guangxi Medical University	Nanning		China	530021
85	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai		China	200025
86	Fudan University Shanghai Cancer Center	Shanghai		China	200032
87	Changhai Hospital of Shanghai	Shanghai		China	200433
88	First Hospital of China Medical University	Shenyang		China	110001
89	The Second Affiliated Hospital of Soochow University	Suzhou		China	215004
90	First Affiliated Hospital of Soochow University	Suzhou		China	215006
91	Tianjin Cancer Hospital	Tianjin		China	300060
92	Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology	Wuhan		China	430022
93	Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center	Wuhan		China	430023
94	The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)	Xi'an		China	710038
95	Fundacion Cardioinfantil	Bogota		Colombia
96	Organizacion Sanitas Internacional	Bogota		Colombia
97	FOSCAL	Floridablanca		Colombia
98	Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika	Brno		Czechia	625 00
99	Fn Hr. Kralove; IV. Interni Hematologicka Klinika	Hradec Kralove		Czechia	500 05
100	Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK	Praha 2		Czechia	128 08
101	Rigshospitalet; Hæmatologisk Klinik	København Ø		Denmark	2100
102	Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium	Roskilde		Denmark	4000
103	Aarhus Universitetshospital, Hæmatologisk Afdeling R	Århus		Denmark	8000
104	Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stammz	Aachen		Germany	52074
105	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin		Germany	10707
106	Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I	Dresden		Germany	01307
107	Friedrich-Alexander-Universität Erlangen-Nürnberg; Medizinische Klinik V	Erlangen		Germany	91054
108	Klinik der Justus-Liebig-Universität; Innere Medizin	Gießen		Germany	35392
109	Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V	Heidelberg		Germany	69120
110	Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie	Würzburg		Germany	97080
111	Pamela Youde Nethersole Eastern Hospital; Department of Medicine	Hong Kong		Hong Kong
112	Queen Mary Hospital; Dept of Medicine	Hong Kong		Hong Kong
113	Semmelweis University, First Dept of Medicine	Budapest		Hungary	1083
114	National Institute of Oncology, A Dept of Internal Medicine	Budapest		Hungary	1122
115	University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B	Debrecen		Hungary	4032
116	Petz Aladar Megyei Korhaz; Hematologia	Gyor		Hungary	9024
117	Kaposi Mor Teaching Hospital, Dept of Internal Medicine/Hematology	Kaposvar		Hungary	7400
118	University of Pecs, I st Dept of Internal Medicine	Pecs		Hungary	7624
119	University of Szeged, II Dept of Internal Medicine	Szeged		Hungary	6720
120	Ospedale Riuniti; Divisione Di Ematologia	Reggio Calabria	Calabria	Italy	89100
121	Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica	Napoli	Campania	Italy	80131
122	Nuovo Policlinico, Ii Facolta; Divisione Di Ematologia	Napoli	Campania	Italy	80131
123	Ospedale "A.Tortora" - Ematologia; Dipartimento Di Ematologia	Pagani (Sa)	Campania	Italy	84016
124	A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna	Bologna	Emilia-Romagna	Italy	40138
125	AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia	Reggio Emilia	Emilia-Romagna	Italy	42100
126	A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica	Udine	Friuli-Venezia Giulia	Italy	33100
127	Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol	Roma	Lazio	Italy	00161
128	A.O. Universitaria S. Martino Di Genova; Ematologia 1	Genova	Liguria	Italy	16132
129	A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia	Brescia	Lombardia	Italy	25123
130	Hospital San Raffaele	Milano	Lombardia	Italy	20132
131	Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico	Milano	Lombardia	Italy	20133
132	Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia	Milano	Lombardia	Italy	20141
133	Irccs Policlinico San Matteo; Divisione Di Ematologia	Pavia	Lombardia	Italy	27100
134	Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia	Alessandria	Piemonte	Italy	15121
135	Ospedali Riuniti del Canavese	Ivrea	Piemonte	Italy	10015
136	Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad	Novara	Piemonte	Italy	28100
137	Az. Osp. S. Luigi Gonzaga; S.C.D.U. Medicina Interna Ii	Orbassano	Piemonte	Italy	10043
138	A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1	Torino	Piemonte	Italy	10126
139	A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia	Torino	Piemonte	Italy	10126
140	Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica	Bari	Puglia	Italy	70124
141	IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo	San Giovanni Rotondo	Puglia	Italy	71013
142	Az. Osp. C. Panico; Rep. Ematologia E Trapianto	Tricase - LE	Puglia	Italy	73039
143	Azienda Ospedaliero Univ	Catania	Sicilia	Italy	95124
144	Az. Osp. Papardo; Struttura Complessa Di Ematologia	Messina	Sicilia	Italy	98165
145	Azienda Ospedaliera Univ	Firenze	Toscana	Italy	50141
146	Ospedale Santa Chiara; Unita Operativa Di Ematologia	Pisa	Toscana	Italy	56100
147	Az. Osp. S. Maria; Dept. Di Oncologia Medica	Terni	Umbria	Italy	05100
148	Ospedale Ca Foncello; Ematologia	Treviso	Veneto	Italy	31100
149	Uni Di Verona Policlinico G.B. Rossi; Divisione E Cattedra Di Ematologia	Verona	Veneto	Italy	37130
150	Ospedale Di Vicenza; Nefrologia, Ematologia	Vicenza	Veneto	Italy	36100
151	Nagoya Daini Red Cross Hospital; Hematology & Oncology	Aichi		Japan	466-8650
152	Chiba University Hospital; Hematology	Chiba		Japan	260-8670
153	Kyushu University Hospital; Hematology, Oncology & Cardiovascular medicine	Fukuoka		Japan	812-8582
154	Kurume University Hospital; Hematology and Oncology	Fukuoka		Japan	830-0011
155	Gifu University Hospital; First Department of Internal Medicine	Gifu		Japan	501-1194
156	Hokkaido University Hospital; Hematology	Hokkaido		Japan	060-8648
157	Kobe City Medical Center General Hospital; Hematology	Hyogo		Japan	650-0047
158	Iwate Medical University Hospital;Hematology and Oncology	Iwate		Japan	020-8505
159	Yokohama City University Hospital; Hematology, Rheumatology, Infectious Disease	Kanagawa		Japan	236-0004
160	Kyoto University Hospital; Department of Hematology/Oncology	Kyoto		Japan	606-8507
161	Niigata Cancer Center Hospital; Internal Medicine	Niigata		Japan	951-8566
162	Kurashiki Central Hospital; Hematology	Okayama		Japan	710-8602
163	Osaka City University Hospital; Hematology	Osaka		Japan	545-8586
164	Osaka University Hospital; Hematology and Oncology	Osaka		Japan	565-0871
165	Kindai University Hospital; Hematology and Rheumatology	Osaka		Japan	589-8511
166	Shimane University Hospital;Hematology	Shimane		Japan	693-8501
167	Jichi Medical University Hospital; Hematology	Tochigi		Japan	329-0498
168	National Cancer Center Hospital; Hematology	Tokyo		Japan	104-0045
169	Toranomon Hospital; Hematology	Tokyo		Japan	105-8470
170	Nippon Medical School Hospital; Hematology	Tokyo		Japan	113-8603
171	The Cancer Institute Hospital of JFCR; Hematology Oncology	Tokyo		Japan	135-8550
172	National Cancer Center	Gyeonggi-do		Korea, Republic of	10408
173	Chonnam National University Hwasun Hospital	Jeollanam-do		Korea, Republic of	58128
174	Seoul National University Hospital	Seoul		Korea, Republic of	03080
175	Asan Medical Center - Oncology	Seoul		Korea, Republic of	05505
176	Yonsei University Severance Hospital; Medical Oncology	Seoul		Korea, Republic of	120-752
177	St. Mary'S Hospital, the Catholic University School of Medicine; Internal Medicine	Seoul		Korea, Republic of	137-701
178	Samsung Medical Center	Seoul		Korea, Republic of	6351
179	Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre	Chihuahua		Mexico	31000
180	Hospital Universitario Dr. Jose E. Gonzalez; Haematology	Monterrey		Mexico	64460
181	Oaxaca Site Management Organization	Oaxaca		Mexico	68000
182	Centro de Estudios Clinicos de Queretaro, SC	Queretaro		Mexico	76000
183	Centro Hemato Oncologico Panama	Panama		Panama	0832
184	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	15038
185	Instituto;Oncologico Miraflores	Lima		Peru	18
186	Clinica de Especialidades Medicas	Lima		Peru	Lima 41
187	Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny	Brzozów		Poland	36-200
188	Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii	Gdansk		Poland	80-952
189	Medical University of Lodz; Hematology	Lodz		Poland	93-510
190	Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie	Lublin		Poland	20-081
191	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego	Warszawa		Poland	02-781
192	Medical Uni of Wroclaw; Hematology	Wroclaw		Poland	50-367
193	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan		Russian Federation	420029
194	Blokhin Cancer Research Center; Clinical Oncology	Moscow		Russian Federation	115478
195	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod		Russian Federation	603126
196	Penza Regional Oncology Dispensary	Penza		Russian Federation	440071
197	Republican Clinical Hospital n.a. Baranov; Haematology	Petrozavodsk		Russian Federation	185019
198	Research Inst. of Hematology & Blood Transfusion ; Hematology	St Petersburg		Russian Federation	191024
199	Institute of Hematology	Belgrade		Serbia	11000
200	Clinical Center Vojvodine; Clinic for Hematology	Novi Sad		Serbia	21000
201	National Oncology Inst. ; Dept. of Haematology	Bratislava		Slovakia	833 10
202	Constantiaberg Medical Clinic; Dept. of Haematology & Bone Marrow Translant	Cape Town		South Africa	7800
203	Mary Potter Oncology Centre	Groenkloof		South Africa	0181
204	Medical Oncology Centre of Rosebank; Oncology	Johannesburg		South Africa	2196
205	Wits Donald Gordon Clinical Trial Centre; Medical Oncology	Parktown, Johannesburg		South Africa	2193
206	Drs Thomson, Brittain an Partners Inc	Pretoria		South Africa	0044
207	Hospital de Navarra, Servicio de Hematología	Pamplona	Navarra	Spain	31008
208	Hospital Universitari Sant Joan de Reus; Servicio de Oncologia	Reus	Tarragona	Spain	43204
209	Hospital del Mar; Servicio de Hematologia	Barcelona		Spain	08003
210	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona		Spain	08035
211	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona		Spain	08036
212	Hospital Duran i Reynals; Servicio de Hematologia	Barcelona		Spain	08907
213	Hospital Ramon y Cajal; Servicio de Hematologia	Madrid		Spain	28034
214	Complejo Hospitalario de Pontevedra; Servicio de Oncologia	Pontevedra		Spain	36002
215	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla		Spain	41009
216	Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia	Toledo		Spain	45004
217	Kantonsspital Aarau; Zentrum Für Onkologie, Hämatologie & Transfusionsmedizin	Aarau		Switzerland	5001
218	Ospedale San Giovanni; Oncologia	Bellinzona		Switzerland	6500
219	Kantonsspital Graubünden;Onkologie und Hämatologie	Chur		Switzerland	7000
220	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich		Switzerland	8091
221	Veterans General Hospital; Division of Oncology	Taipei		Taiwan	00112
222	National Taiwan Universtiy Hospital; Division of Hematology	Taipei		Taiwan	100
223	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei		Taiwan	112
224	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan		Taiwan	333
225	King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10330
226	National Cancer Inst.	Bangkok		Thailand	10400
227	Rajavithi Hospital; Medicine	Bangkok		Thailand	10400
228	Ramathibodi Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10400
229	Siriraj Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10700
230	Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine	Khon Kaen		Thailand	40002
231	Aberdeen Royal Infirmary; Haematology - Ward 16	Aberdeen		United Kingdom	AB25 2ZN
232	Birmingham Heartlands Hospital; Department of Haematology	Birmingham		United Kingdom	B9 5SS
233	Addenbrookes Hospital; Haematology	Cambridge		United Kingdom	CB2 0QQ
234	The HOPE Clinical Trials Unit	Leicester		United Kingdom	LE1 5WW
235	New Cross Hospital; Dept. Of Haematology	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

Hoffmann-La Roche
Fondazione Italiana Linfomi ONLUS

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01287741

Other Study ID Numbers:

BO21005
2010-024194-39

First Posted:

Feb 1, 2011

Last Update Posted:

Apr 12, 2019

Last Verified:

Apr 1, 2019

Additional relevant MeSH terms:

Lymphoma

Lymphoma, B-Cell

Lymphoma, Large B-Cell, Diffuse

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	A total of 1418 patients were randomized and included in the primary analyses (29 April 2016). A total of 1414 patients were included in the final analysis (31 January 2018), 710 in the R-CHOP arm and 704 in the G-CHOP arm; data from 4 patients were excluded because of serious GCP non-compliance at a single study site in China.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Period Title: Overall Study
STARTED	712	706
COMPLETED	86	91
NOT COMPLETED	626	615

Baseline Characteristics

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy	Total
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Total of all reporting groups
Overall Participants	710	704	1414
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (13.6)	59.4 (13.3)	59.2 (13.5)
Sex: Female, Male (Count of Participants)
Female	328 46.2%	336 47.7%	664 47%
Male	382 53.8%	368 52.3%	750 53%

Outcome Measures

1. Primary Outcome

Title	Median Time to Progression-Free Survival (PFS), Investigator-Assessed
Description	Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]). Progression-free survival was defined as the time from randomization until the first documented day of disease progression or relapse, using a modified version of the Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).
Time Frame	Baseline up to approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Median (95% Confidence Interval) [months]	74.5	68.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab+Chemotherapy, Obinutuzumab+Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4753
	Comments
	Method	Log Rank
	Comments	Stratified by International Prognostic Index (IPI) score (low/low-intermediate (excluding participants having an IPI score 0 without bulky disease).

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95% 0.78 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Median Time to Progression-Free Survival (PFS), Independent Review Committee (IRC)-Assessed
Description	Kaplan Meier estimate of median PFS was defined as time at which half of participants have progressed (progressive disease [PD]). Progression-free survival was defined as time from randomization until first documented day of disease progression or relapse, using a modified version of Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on basis of IRC assessments. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 cm or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT or MRI. This outcome measure used data from primary analysis which included all 1418 participants.
Time Frame	Baseline up to approximately 4 years and 9 months (up to 29 April 2016)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	712	706
Median (95% Confidence Interval) [months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab+Chemotherapy, Obinutuzumab+Chemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2736
	Comments
	Method	Log Rank
	Comments	Stratified by International Prognostic Index (IPI) score (low/low-intermediate (excluding participants having an IPI score 0 without bulky disease).

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95% 0.72 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Median Time to Overall Survival (OS)
Description	Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death. Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause.
Time Frame	Baseline up to approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Median (95% Confidence Interval) [months]	NA	NA

4. Secondary Outcome

Title	Overall Response Rate (ORR), Investigator-Assessed
Description	Overall response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.
Time Frame	Baseline up to approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Without PET	80.1 11.3%	81.4 11.6%
With PET	77.6 10.9%	77.1 11%

5. Secondary Outcome

Title	Overall Response Rate (ORR), IRC-Assessed
Description	Overall response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites. This outcome measure used data from primary analysis which included all 1418 participants.
Time Frame	Baseline up to approximately 4 years and 9 months (up to 29 April 2016)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	712	706
Without PET	80.2 11.3%	82.3 11.7%
With PET	81.1 11.4%	82.1 11.7%

6. Secondary Outcome

Title	Complete Response (CR) at the End of Treatment, Investigator-Assessed
Description	Percentage of participants with complete response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease.
Time Frame	Baseline up to approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Without PET	33.9 4.8%	35.4 5%
With PET	59.1 8.3%	56.5 8%

7. Secondary Outcome

Title	Complete Response (CR) at the End of Treatment, IRC-Assessed
Description	Percentage of participants with complete response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease. This outcome measure used data from primary analysis which included all 1418 participants.
Time Frame	Baseline up to approximately 4 years and 9 months (up to 29 April 2016)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	712	706
Without PET	34.4 4.8%	39.1 5.6%
With PET	65.3 9.2%	66.7 9.5%

8. Secondary Outcome

Title	Median Time to Event-Free Survival (EFS), Investigator-Assessed
Description	Kaplan Meier estimate of median EFS is the time at which half of the participants have progressed. Event-free survival was defined as the time from the date of randomization until the date of disease progression, relapse, initiation of a new non-protocol-specified anti-lymphoma treatment, or death from any cause on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.
Time Frame	Baseline up to death or disease progression, or initiation of new anti-lymphoma treatment (NALT), whichever occurred first, approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Mean (95% Confidence Interval) [months]	74.5	68.3

9. Secondary Outcome

Title	Median Time to Disease-Free Survival (DFS), Investigator-Assessed
Description	Kaplan Meier estimate of median DFS was defined as time at which half of participants have disease progression/relapse or death from any cause. Disease-free survival was defined as time from date of the first occurrence of a documented CR to date of disease progression/relapse or death from any cause on basis of investigator assessments with use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.
Time Frame	Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, of which evaluable participants were included in this analysis, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	394	417
Median (95% Confidence Interval) [months]	NA	65.4

10. Secondary Outcome

Title	Duration of Response (DOR), Investigator-Assessed
Description	DOR: time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with CT/MRI. CR: disappearance of all target lesions. PR: >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodule regression >/= 50%. Progression/relapse: at least 50% increase in nodal lesions or >/=50% increase in any node > 1 cm or >/= 50% increase in other target lesions (e.g., splenic or hepatic nodules) and/or any new bone marrow involvement and/or any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. A participant in the Rituximab+CHOP arm with the longest follow-up, 53 months, had an event. The criterion for median was the minimum time when survival went below 50%.
Time Frame	Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, of which evaluable participants were included in this analysis, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	641	657
Median (95% Confidence Interval) [months]	71.9	NA

11. Secondary Outcome

Title	Time to Next Anti-Lymphoma Treatment (TTNALT)
Description	Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause.
Time Frame	Baseline up to start of next anti-lymphoma treatment or death due to any cause, whichever occurred first, approximately 6.5 years (31 January 2018)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants, however because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Median (95% Confidence Interval) [months]	NA	NA

12. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Baseline up to approximately 6.5 years (up to 31 January 2018)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least one dose of study drug. Because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	701	702
Number [percentage of participants]	95.3 13.4%	98.1 13.9%

13. Secondary Outcome

Title	Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Description	The presence of HAHAs to obinutuzumab was assessed in the first 100 randomized participants.
Time Frame	Pre-dose (Hour 0) on Cycle (C) 4 Day (D) 1, at end of treatment/early termination (up to Month 6), every 6 months thereafter for 30 months (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description
The safety analysis population included all participants who received at least one dose of study drug. Because of serious Good Clinical Practice non- compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	100
Screening	2.0 0.3%
Cycle 4 Day 1	0 0%
Study Completion / Early Discontinuation	0 0%
Follow-Up Month 6	0 0%
Follow-Up Month 12	0 0%
Follow-Up Month 18	0 0%
Follow-Up Month 24	0 0%
Follow-Up Month 30	0 0%
Follow-Up Completion/ Early Discontinuation	0 0%
Unscheduled	0 0%

14. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale Score
Description	The FACT-Lym subscale was developed to assess health-related quality of life in participants with non-Hodgkin lymphoma. The score range is 0-60, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement.
Time Frame	Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to approximately 6.5 years, (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants. Because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	706
Baseline	45.34 (10.16)	45.18 (9.86)
Score Change, Cycle 3 Day 1	3.83 (8.65)	3.70 (9.13)
Score Change, Study Compl./Discont.	5.03 (10.21)	4.35 (11.03)
Score Change, Follow-Up Month 12	6.37 (10.12)	6.18 (10.51)
Score Change, Follow-Up Month 24	7.07 (10.35)	6.66 (10.50)
Score Change, Follow-Up Month 30	25.00 (NA)
Score Change, Follow-Up Month 36	7.57 (10.16)	7.31 (10.67)
Score Change, Follow-Up Month 48	8.22 (9.65)	7.37 (10.45)
Score Change, Follow-Up Term./Compl.	5.51 (10.04)	5.55 (10.62)

15. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores
Description	The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
Time Frame	Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to data cut-off, up to approximately 6.5 years, (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description
The intent-to-treat (ITT) population included all randomized participants. Because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 participants enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	710	704
Baseline	59.81 (24.39)	58.55 (25.23)
Change Baseline, Cycle 3 Day 1	6.37 (23.77)	7.51 (25.99)
Change Baseline, Study Completion	9.84 (25.96)	10.22 (30.17)
Change Baseline, Follow-Up Month 12	12.67 (26.31)	13.84 (29.97)
Change Baseline, Follow-Up Month 24	14.74 (26.33)	15.81 (29.24)
Change Baseline, Follow-Up Month 30	58.33 (NA)
Change Baseline, Follow-Up Month 36	15.01 (26.85)	17.99 (28.85)
Change Baseline, Follow-Up Month 48	16.62 (27.49)	17.53 (30.31)
Change Baseline, Follow-Up Completion	8.74 (29.40)	8.46 (28.71)

16. Secondary Outcome

Title	Serum Concentrations of Obinutuzumab in Japanese Participants With Diffuse Large B-Cell Lymphoma (DLBCL)
Description	Serum samples for assessment of obinutuzumab serum concentrations were collected only from a subset of Japanese participants following administration of 1000 mg obinutuzumab.
Time Frame	C1: D1 post-infusion and 20-28 and 66-80 hours after end of infusion, D8 and D15 pre-and post-infusion; C2: D1 pre- and post-infusion; C4: D1 pre- and post-infusion; C6: D1 pre- and post-infusion; C8: D1 pre- and post-infusion (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description
The Pharmacokinetic assessment was done on a subset of 39 Japanese participants in the Obinutuzumab+Chemotherapy arm only.

Arm/Group Title	Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
Measure Participants	39
Cycle 1, Day 8 pre-infusion	174 (38.7)
Cycle 1, Day 15 pre-infusion	320 (39.2)
Cycle 2, Day 1 pre-infusion	431 (39.8)
Cycle 4, Day 1 pre-infusion	352 (42.1)
Cycle 6, Day 1 pre-infusion	378 (45.9)
Cycle 8, Day 1 pre-infusion	478 (43.9)
Cycle 1, Day 1 post-infusion	435 (32.3)
Cycle 1, Day 1 20-28 hours after end of infusion	259 (56.3)
Cycle 1, Day 1 66-80 hours after end of infusion	219 (51.2)
Cycle 1, Day 8 post-infusion	578 (37.8)
Cycle 1, Day 15 post-infusion	718 (32.9)
Cycle 2, Day 1 post-infusion	938 (31.3)
Cycle 4, Day 1 post-infusion	817 (28.6)
Cycle 6, Day 1 post-infusion	813 (32.6)
Cycle 8, Day 1 post-infusion	881 (35.9)

Adverse Events

	Rituximab+Chemotherapy		Obinutuzumab+Chemotherapy
Time Frame	6 years and 7 months
Adverse Event Reporting Description	The safety analysis population included all participants who received at least one dose of study drug (i.e., obinutuzumab, rituximab, or CHOP). Because of serious Good Clinical Practice non-compliance at a single study site in China, all 4 patients enrolled at the site (2 in each treatment arm) were excluded from the final analysis.

Arm/Group Title	Rituximab+Chemotherapy		Obinutuzumab+Chemotherapy
Arm/Group Description	Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.		Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab+Chemotherapy		Obinutuzumab+Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	269/701 (38.4%)		312/702 (44.4%)
Blood and lymphatic system disorders
Anaemia	6/701 (0.9%)		9/702 (1.3%)
Febrile neutropenia	71/701 (10.1%)		85/702 (12.1%)
Haemolytic anaemia	1/701 (0.1%)		0/702 (0%)
Histiocytosis haematophagic	0/701 (0%)		1/702 (0.1%)
Immune thrombocytopenic purpura	0/701 (0%)		1/702 (0.1%)
Leukopenia	6/701 (0.9%)		14/702 (2%)
Neutropenia	38/701 (5.4%)		54/702 (7.7%)
Splenic haematoma	0/701 (0%)		1/702 (0.1%)
Thrombocytopenia	2/701 (0.3%)		12/702 (1.7%)
Bone Marrow Failure	1/701 (0.1%)		0/702 (0%)
Cardiac disorders
Acute coronary syndrome	0/701 (0%)		1/702 (0.1%)
Acute myocardial infarction	5/701 (0.7%)		2/702 (0.3%)
Angina pectoris	2/701 (0.3%)		0/702 (0%)
Atrial fibrillation	4/701 (0.6%)		9/702 (1.3%)
Atrial flutter	1/701 (0.1%)		1/702 (0.1%)
Bradycardia	0/701 (0%)		1/702 (0.1%)
Cardiac arrest	1/701 (0.1%)		1/702 (0.1%)
Cardiac failure	3/701 (0.4%)		7/702 (1%)
Cardiac failure congestive	1/701 (0.1%)		3/702 (0.4%)
Cardiac perforation	0/701 (0%)		1/702 (0.1%)
Cardiomyopathy	0/701 (0%)		1/702 (0.1%)
Cardiopulmonary failure	1/701 (0.1%)		0/702 (0%)
Congestive cardiomyopathy	1/701 (0.1%)		0/702 (0%)
Coronary artery disease	1/701 (0.1%)		0/702 (0%)
Coronary artery thrombosis	0/701 (0%)		1/702 (0.1%)
Hypertensive heart disease	0/701 (0%)		1/702 (0.1%)
Left ventricular dysfunction	0/701 (0%)		1/702 (0.1%)
Mitral valve disease	0/701 (0%)		1/702 (0.1%)
Myocardial infarction	2/701 (0.3%)		3/702 (0.4%)
Myocardial ischaemia	1/701 (0.1%)		0/702 (0%)
Pericardial effusion	0/701 (0%)		1/702 (0.1%)
Supraventricular tachycardia	1/701 (0.1%)		0/702 (0%)
Ventricular flutter	0/701 (0%)		1/702 (0.1%)
Ear and labyrinth disorders
Vertigo positional	0/701 (0%)		1/702 (0.1%)
Endocrine disorders
Addison's disease	0/701 (0%)		1/702 (0.1%)
Goitre	1/701 (0.1%)		0/702 (0%)
Eye disorders
Cataract	2/701 (0.3%)		0/702 (0%)
Lacrimation increased	0/701 (0%)		1/702 (0.1%)
Gastrointestinal disorders
Abdominal pain	6/701 (0.9%)		4/702 (0.6%)
Abdominal pain upper	1/701 (0.1%)		2/702 (0.3%)
Anal fistula	1/701 (0.1%)		0/702 (0%)
Colitis	2/701 (0.3%)		2/702 (0.3%)
Constipation	1/701 (0.1%)		0/702 (0%)
Diarrhoea	6/701 (0.9%)		5/702 (0.7%)
Dysphagia	0/701 (0%)		1/702 (0.1%)
Gastric haemorrhage	2/701 (0.3%)		1/702 (0.1%)
Gastric perforation	3/701 (0.4%)		1/702 (0.1%)
Gastric ulcer	0/701 (0%)		1/702 (0.1%)
Gastritis	0/701 (0%)		1/702 (0.1%)
Gastritis haemorrhagic	0/701 (0%)		1/702 (0.1%)
Gastrointestinal haemorrhage	3/701 (0.4%)		2/702 (0.3%)
Haematemesis	0/701 (0%)		1/702 (0.1%)
Haematochezia	1/701 (0.1%)		0/702 (0%)
Haemorrhoids	0/701 (0%)		2/702 (0.3%)
Ileal perforation	0/701 (0%)		1/702 (0.1%)
Ileus	2/701 (0.3%)		1/702 (0.1%)
Ileus paralytic	1/701 (0.1%)		0/702 (0%)
Impaired gastric emptying	1/701 (0.1%)		0/702 (0%)
Inguinal hernia	1/701 (0.1%)		1/702 (0.1%)
Intestinal ischaemia	0/701 (0%)		1/702 (0.1%)
Intestinal obstruction	5/701 (0.7%)		2/702 (0.3%)
Intestinal perforation	3/701 (0.4%)		3/702 (0.4%)
Large intestine polyp	0/701 (0%)		2/702 (0.3%)
Lower gastrointestinal haemorrhage	1/701 (0.1%)		0/702 (0%)
Melaena	1/701 (0.1%)		0/702 (0%)
Nausea	2/701 (0.3%)		1/702 (0.1%)
Pancreatitis acute	0/701 (0%)		1/702 (0.1%)
Pneumoperitoneum	0/701 (0%)		1/702 (0.1%)
Small intestinal obstruction	1/701 (0.1%)		2/702 (0.3%)
Small intestinal perforation	1/701 (0.1%)		1/702 (0.1%)
Stomatitis	1/701 (0.1%)		0/702 (0%)
Subileus	1/701 (0.1%)		1/702 (0.1%)
Upper gastrointestinal haemorrhage	1/701 (0.1%)		3/702 (0.4%)
Vomiting	2/701 (0.3%)		2/702 (0.3%)
General disorders
Asthenia	4/701 (0.6%)		2/702 (0.3%)
Axillary pain	0/701 (0%)		1/702 (0.1%)
Chest pain	2/701 (0.3%)		0/702 (0%)
Chills	1/701 (0.1%)		2/702 (0.3%)
Death	2/701 (0.3%)		3/702 (0.4%)
Extravasation	1/701 (0.1%)		0/702 (0%)
Fatigue	5/701 (0.7%)		4/702 (0.6%)
General physical health deterioration	1/701 (0.1%)		2/702 (0.3%)
Hernia	0/701 (0%)		1/702 (0.1%)
Hyperpyrexia	0/701 (0%)		1/702 (0.1%)
Incarcerated hernia	0/701 (0%)		1/702 (0.1%)
Malaise	0/701 (0%)		2/702 (0.3%)
Mucosal inflammation	1/701 (0.1%)		1/702 (0.1%)
Non-cardiac chest pain	2/701 (0.3%)		0/702 (0%)
Oedema peripheral	0/701 (0%)		2/702 (0.3%)
Pain	1/701 (0.1%)		0/702 (0%)
Peripheral swelling	1/701 (0.1%)		0/702 (0%)
Pyrexia	11/701 (1.6%)		17/702 (2.4%)
Sudden death	1/701 (0.1%)		1/702 (0.1%)
Hepatobiliary disorders
Bile duct obstruction	0/701 (0%)		1/702 (0.1%)
Cholecystitis	2/701 (0.3%)		1/702 (0.1%)
Cholecystitis acute	1/701 (0.1%)		1/702 (0.1%)
Cholelithiasis	1/701 (0.1%)		0/702 (0%)
Hepatic function abnormal	1/701 (0.1%)		0/702 (0%)
Infections and infestations
Anal abscess	0/701 (0%)		2/702 (0.3%)
Appendiceal abscess	0/701 (0%)		1/702 (0.1%)
Appendicitis	3/701 (0.4%)		1/702 (0.1%)
Atypical pneumonia	2/701 (0.3%)		0/702 (0%)
Bacterial infection	1/701 (0.1%)		0/702 (0%)
Bacterial sepsis	0/701 (0%)		1/702 (0.1%)
Bronchitis	4/701 (0.6%)		1/702 (0.1%)
Bronchopulmonary aspergillosis	1/701 (0.1%)		1/702 (0.1%)
Candida sepsis	1/701 (0.1%)		0/702 (0%)
Cellulitis	2/701 (0.3%)		2/702 (0.3%)
Cholecystitis infective	0/701 (0%)		1/702 (0.1%)
Clostridium difficile colitis	1/701 (0.1%)		1/702 (0.1%)
Clostridium difficile infection	0/701 (0%)		1/702 (0.1%)
Cytomegalovirus chorioretinitis	1/701 (0.1%)		3/702 (0.4%)
Cytomegalovirus colitis	0/701 (0%)		1/702 (0.1%)
Cytomegalovirus infection	2/701 (0.3%)		0/702 (0%)
Device related infection	2/701 (0.3%)		1/702 (0.1%)
Device related sepsis	0/701 (0%)		1/702 (0.1%)
Diabetic foot infection	1/701 (0.1%)		0/702 (0%)
Diarrhoea infectious	0/701 (0%)		2/702 (0.3%)
Diverticulitis	0/701 (0%)		1/702 (0.1%)
Enterobacter infection	0/701 (0%)		1/702 (0.1%)
Enterocolitis infectious	0/701 (0%)		1/702 (0.1%)
Escherichia sepsis	1/701 (0.1%)		0/702 (0%)
Fungal infection	1/701 (0.1%)		0/702 (0%)
Gastroenteritis	3/701 (0.4%)		2/702 (0.3%)
H1N1 influenza	0/701 (0%)		1/702 (0.1%)
Hepatitis B Reactivation	0/701 (0%)		1/702 (0.1%)
Herpes simplex	0/701 (0%)		1/702 (0.1%)
Herpes virus infection	0/701 (0%)		2/702 (0.3%)
Herpes zoster	3/701 (0.4%)		4/702 (0.6%)
Herpes zoster disseminated	0/701 (0%)		1/702 (0.1%)
Infected lymphocele	0/701 (0%)		1/702 (0.1%)
Infection	0/701 (0%)		2/702 (0.3%)
Infectious pleural effusion	0/701 (0%)		2/702 (0.3%)
Infective glossitis	0/701 (0%)		1/702 (0.1%)
Influenza	2/701 (0.3%)		1/702 (0.1%)
Klebsiella sepsis	1/701 (0.1%)		1/702 (0.1%)
Laryngitis	0/701 (0%)		1/702 (0.1%)
Localised infection	1/701 (0.1%)		0/702 (0%)
Lower respiratory tract infection	1/701 (0.1%)		3/702 (0.4%)
Lung infection	3/701 (0.4%)		6/702 (0.9%)
Measles	0/701 (0%)		1/702 (0.1%)
Meningitis	0/701 (0%)		1/702 (0.1%)
Meningitis cryptococcal	1/701 (0.1%)		0/702 (0%)
Meningitis viral	0/701 (0%)		1/702 (0.1%)
Nasopharyngitis	2/701 (0.3%)		0/702 (0%)
Necrotising fasciitis	1/701 (0.1%)		0/702 (0%)
Neutropenic infection	1/701 (0.1%)		1/702 (0.1%)
Neutropenic sepsis	3/701 (0.4%)		3/702 (0.4%)
Oral infection	2/701 (0.3%)		0/702 (0%)
Orchitis	1/701 (0.1%)		0/702 (0%)
Osteomyelitis	1/701 (0.1%)		1/702 (0.1%)
Peritonitis	2/701 (0.3%)		2/702 (0.3%)
Pharyngitis streptococcal	0/701 (0%)		1/702 (0.1%)
Pneumocystis jirovecii pneumonia	3/701 (0.4%)		1/702 (0.1%)
Pneumonia	33/701 (4.7%)		43/702 (6.1%)
Pneumonia bacterial	0/701 (0%)		1/702 (0.1%)
Progressive multifocal leukoencephalopathy	0/701 (0%)		1/702 (0.1%)
Prostatic abscess	1/701 (0.1%)		0/702 (0%)
Pseudomonal sepsis	1/701 (0.1%)		0/702 (0%)
Pulmonary sepsis	1/701 (0.1%)		0/702 (0%)
Rectal abscess	1/701 (0.1%)		1/702 (0.1%)
Respiratory tract infection	0/701 (0%)		2/702 (0.3%)
Scrotal abscess	1/701 (0.1%)		0/702 (0%)
Sepsis	10/701 (1.4%)		16/702 (2.3%)
Sepsis syndrome	0/701 (0%)		1/702 (0.1%)
Septic shock	3/701 (0.4%)		12/702 (1.7%)
Sinusitis fungal	0/701 (0%)		1/702 (0.1%)
Soft tissue infection	1/701 (0.1%)		0/702 (0%)
Subcutaneous abscess	0/701 (0%)		1/702 (0.1%)
Tuberculosis	1/701 (0.1%)		0/702 (0%)
Tuberculosis of central nervous system	1/701 (0.1%)		0/702 (0%)
Upper respiratory tract infection	1/701 (0.1%)		1/702 (0.1%)
Urinary tract infection	3/701 (0.4%)		3/702 (0.4%)
Urosepsis	1/701 (0.1%)		1/702 (0.1%)
Varicella	1/701 (0.1%)		1/702 (0.1%)
Viral infection	0/701 (0%)		1/702 (0.1%)
Viral pharyngitis	1/701 (0.1%)		0/702 (0%)
Wound infection	0/701 (0%)		1/702 (0.1%)
Anorectal cellulitis	1/701 (0.1%)		0/702 (0%)
Gastrointestinal Infection	1/701 (0.1%)		0/702 (0%)
Injury, poisoning and procedural complications
Abdominal wound dehiscence	1/701 (0.1%)		0/702 (0%)
Facial bones fracture	1/701 (0.1%)		0/702 (0%)
Fall	0/701 (0%)		1/702 (0.1%)
Femoral neck fracture	1/701 (0.1%)		0/702 (0%)
Femur fracture	2/701 (0.3%)		1/702 (0.1%)
Fracture	0/701 (0%)		1/702 (0.1%)
Hip fracture	1/701 (0.1%)		1/702 (0.1%)
Infusion related reaction	1/701 (0.1%)		8/702 (1.1%)
Kidney rupture	1/701 (0.1%)		0/702 (0%)
Lumbar vertebral fracture	1/701 (0.1%)		0/702 (0%)
Nerve injury	0/701 (0%)		1/702 (0.1%)
Pelvic fracture	0/701 (0%)		1/702 (0.1%)
Postoperative respiratory failure	0/701 (0%)		1/702 (0.1%)
Procedural complication	0/701 (0%)		1/702 (0.1%)
Spinal compression fracture	1/701 (0.1%)		0/702 (0%)
Subdural haematoma	0/701 (0%)		3/702 (0.4%)
Toxicity to various agents	0/701 (0%)		1/702 (0.1%)
Vascular pseudoaneurysm	1/701 (0.1%)		0/702 (0%)
Wound haemorrhage	0/701 (0%)		1/702 (0.1%)
Compression fracture	0/701 (0%)		1/702 (0.1%)
Investigations
Ejection fraction decreased	0/701 (0%)		1/702 (0.1%)
HIV antibody positive	0/701 (0%)		1/702 (0.1%)
Oxygen saturation decreased	1/701 (0.1%)		0/702 (0%)
Metabolism and nutrition disorders
Cachexia	0/701 (0%)		1/702 (0.1%)
Decreased appetite	1/701 (0.1%)		2/702 (0.3%)
Dehydration	4/701 (0.6%)		5/702 (0.7%)
Diabetes mellitus	0/701 (0%)		1/702 (0.1%)
Failure to thrive	3/701 (0.4%)		0/702 (0%)
Hyperglycaemia	1/701 (0.1%)		0/702 (0%)
Hyperkalaemia	0/701 (0%)		1/702 (0.1%)
Hypokalaemia	2/701 (0.3%)		2/702 (0.3%)
Hyponatraemia	2/701 (0.3%)		0/702 (0%)
Hypophosphataemia	1/701 (0.1%)		0/702 (0%)
Malnutrition	2/701 (0.3%)		1/702 (0.1%)
Tumour lysis syndrome	2/701 (0.3%)		1/702 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/701 (0.3%)		1/702 (0.1%)
Back pain	1/701 (0.1%)		2/702 (0.3%)
Costochondritis	1/701 (0.1%)		0/702 (0%)
Intervertebral disc protrusion	0/701 (0%)		1/702 (0.1%)
Joint swelling	1/701 (0.1%)		0/702 (0%)
Myalgia	0/701 (0%)		1/702 (0.1%)
Osteoarthritis	0/701 (0%)		1/702 (0.1%)
Pain in extremity	1/701 (0.1%)		0/702 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	2/701 (0.3%)		1/702 (0.1%)
Adenocarcinoma of colon	2/701 (0.3%)		0/702 (0%)
B-cell lymphoma	1/701 (0.1%)		0/702 (0%)
Breast cancer	3/701 (0.4%)		1/702 (0.1%)
Colon adenoma	0/701 (0%)		1/702 (0.1%)
Colon cancer	2/701 (0.3%)		0/702 (0%)
Colorectal cancer	1/701 (0.1%)		1/702 (0.1%)
Hepatocellular carcinoma	1/701 (0.1%)		2/702 (0.3%)
Liposarcoma	0/701 (0%)		1/702 (0.1%)
Lung adenocarcinoma	2/701 (0.3%)		3/702 (0.4%)
Marginal zone lymphoma	1/701 (0.1%)		0/702 (0%)
Oesophageal carcinoma	1/701 (0.1%)		0/702 (0%)
Papillary cystadenoma lymphomatosum	0/701 (0%)		1/702 (0.1%)
Prostate cancer	2/701 (0.3%)		2/702 (0.3%)
Small cell lung cancer metastatic	0/701 (0%)		1/702 (0.1%)
Tumour perforation	0/701 (0%)		1/702 (0.1%)
Angioimmuoblastic T-cell lymphoma	0/701 (0%)		1/702 (0.1%)
Myelodysplastic syndrome	0/701 (0%)		1/702 (0.1%)
Squamous cell carincoma of pharynx	1/701 (0.1%)		0/702 (0%)
Lung neoplasm malignant	0/701 (0%)		1/702 (0.1%)
Plasma cell myeloma	1/701 (0.1%)		0/702 (0%)
Nervous system disorders
Amyotrophic lateral sclerosis	0/701 (0%)		1/702 (0.1%)
Cerebral haemorrhage	0/701 (0%)		1/702 (0.1%)
Cerebral infarction	1/701 (0.1%)		0/702 (0%)
Cerebral ischaemia	1/701 (0.1%)		1/702 (0.1%)
Cerebrovascular accident	2/701 (0.3%)		3/702 (0.4%)
Depressed level of consciousness	0/701 (0%)		1/702 (0.1%)
Dizziness	0/701 (0%)		2/702 (0.3%)
Embolic stroke	1/701 (0.1%)		0/702 (0%)
Epilepsy	1/701 (0.1%)		0/702 (0%)
Headache	2/701 (0.3%)		3/702 (0.4%)
Hemiparesis	0/701 (0%)		1/702 (0.1%)
Iiird nerve paralysis	0/701 (0%)		1/702 (0.1%)
Ischaemic stroke	0/701 (0%)		1/702 (0.1%)
Loss of consciousness	1/701 (0.1%)		0/702 (0%)
Neuropathy peripheral	1/701 (0.1%)		1/702 (0.1%)
Peripheral motor neuropathy	1/701 (0.1%)		0/702 (0%)
Peripheral sensory neuropathy	1/701 (0.1%)		0/702 (0%)
Polyneuropathy	1/701 (0.1%)		0/702 (0%)
Presyncope	1/701 (0.1%)		2/702 (0.3%)
Stroke in evolution	0/701 (0%)		1/702 (0.1%)
Syncope	3/701 (0.4%)		0/702 (0%)
Toxic encephalopathy	1/701 (0.1%)		0/702 (0%)
Transient ischaemic attack	1/701 (0.1%)		0/702 (0%)
Vocal cord paralysis	1/701 (0.1%)		0/702 (0%)
Seizure	0/701 (0%)		1/702 (0.1%)
Psychiatric disorders
Anxiety	0/701 (0%)		1/702 (0.1%)
Completed suicide	0/701 (0%)		1/702 (0.1%)
Delirium	0/701 (0%)		1/702 (0.1%)
Depression	1/701 (0.1%)		0/702 (0%)
Emotional distress	0/701 (0%)		1/702 (0.1%)
Mental status changes	0/701 (0%)		1/702 (0.1%)
Renal and urinary disorders
Acute kidney injury	2/701 (0.3%)		2/702 (0.3%)
Cystitis glandularis	0/701 (0%)		1/702 (0.1%)
Haematuria	0/701 (0%)		2/702 (0.3%)
Renal colic	1/701 (0.1%)		0/702 (0%)
Renal failure	1/701 (0.1%)		1/702 (0.1%)
Renal impairment	0/701 (0%)		1/702 (0.1%)
Urinary retention	0/701 (0%)		1/702 (0.1%)
Reproductive system and breast disorders
Uterine haemorrhage	0/701 (0%)		1/702 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acquired tracheo-oesophageal fistula	0/701 (0%)		1/702 (0.1%)
Acute pulmonary oedema	0/701 (0%)		1/702 (0.1%)
Acute respiratory distress syndrome	1/701 (0.1%)		1/702 (0.1%)
Acute respiratory failure	3/701 (0.4%)		1/702 (0.1%)
Alveolitis	0/701 (0%)		1/702 (0.1%)
Asthma	0/701 (0%)		1/702 (0.1%)
Bronchial obstruction	1/701 (0.1%)		0/702 (0%)
Bronchospasm	1/701 (0.1%)		1/702 (0.1%)
Chronic obstructive pulmonary disease	1/701 (0.1%)		2/702 (0.3%)
Dyspnoea	1/701 (0.1%)		2/702 (0.3%)
Dyspnoea exertional	0/701 (0%)		1/702 (0.1%)
Emphysema	0/701 (0%)		2/702 (0.3%)
Haemoptysis	0/701 (0%)		1/702 (0.1%)
Haemothorax	0/701 (0%)		1/702 (0.1%)
Hypoxia	1/701 (0.1%)		1/702 (0.1%)
Interstitial lung disease	6/701 (0.9%)		3/702 (0.4%)
Lung infiltration	0/701 (0%)		1/702 (0.1%)
Organising pneumonia	1/701 (0.1%)		0/702 (0%)
Pleural effusion	2/701 (0.3%)		4/702 (0.6%)
Pneumonia aspiration	0/701 (0%)		1/702 (0.1%)
Pneumonitis	1/701 (0.1%)		5/702 (0.7%)
Pneumothorax	1/701 (0.1%)		1/702 (0.1%)
Pulmonary embolism	4/701 (0.6%)		4/702 (0.6%)
Pulmonary fibrosis	0/701 (0%)		1/702 (0.1%)
Pulmonary oedema	0/701 (0%)		1/702 (0.1%)
Respiratory failure	2/701 (0.3%)		0/702 (0%)
Cough	0/701 (0%)		1/702 (0.1%)
Skin and subcutaneous tissue disorders
Diabetic foot	1/701 (0.1%)		0/702 (0%)
Skin ulcer	1/701 (0.1%)		2/702 (0.3%)
Vascular disorders
Deep vein thrombosis	0/701 (0%)		2/702 (0.3%)
Haemorrhage	0/701 (0%)		1/702 (0.1%)
Hypertension	0/701 (0%)		1/702 (0.1%)
Hypotension	2/701 (0.3%)		3/702 (0.4%)
Orthostatic hypotension	1/701 (0.1%)		0/702 (0%)
Phlebitis	0/701 (0%)		1/702 (0.1%)
Thrombophlebitis	2/701 (0.3%)		0/702 (0%)
Thrombophlebitis superficial	0/701 (0%)		1/702 (0.1%)
Venous occlusion	0/701 (0%)		1/702 (0.1%)
Venous thrombosis limb	0/701 (0%)		1/702 (0.1%)
Axillary vein thrombosis	1/701 (0.1%)		0/702 (0%)
Jugular vein thrombosis	1/701 (0.1%)		0/702 (0%)
Subclavian vein thrombosis	1/701 (0.1%)		0/702 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab+Chemotherapy		Obinutuzumab+Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	613/701 (87.4%)		646/702 (92%)
Blood and lymphatic system disorders
Anaemia	101/701 (14.4%)		96/702 (13.7%)
Febrile neutropenia	44/701 (6.3%)		52/702 (7.4%)
Leukopenia	90/701 (12.8%)		117/702 (16.7%)
Neutropenia	269/701 (38.4%)		315/702 (44.9%)
Thrombocytopenia	16/701 (2.3%)		58/702 (8.3%)
Gastrointestinal disorders
Abdominal pain	47/701 (6.7%)		47/702 (6.7%)
Abdominal pain upper	41/701 (5.8%)		38/702 (5.4%)
Constipation	177/701 (25.2%)		167/702 (23.8%)
Diarrhoea	91/701 (13%)		113/702 (16.1%)
Dyspepsia	43/701 (6.1%)		44/702 (6.3%)
Nausea	199/701 (28.4%)		210/702 (29.9%)
Stomatitis	65/701 (9.3%)		47/702 (6.7%)
Vomiting	75/701 (10.7%)		105/702 (15%)
General disorders
Asthenia	74/701 (10.6%)		76/702 (10.8%)
Chills	37/701 (5.3%)		132/702 (18.8%)
Fatigue	124/701 (17.7%)		136/702 (19.4%)
Mucosal inflammation	36/701 (5.1%)		45/702 (6.4%)
Oedema peripheral	40/701 (5.7%)		35/702 (5%)
Pyrexia	75/701 (10.7%)		137/702 (19.5%)
Infections and infestations
Upper respiratory tract infection	49/701 (7%)		43/702 (6.1%)
Injury, poisoning and procedural complications
Infusion related reaction	162/701 (23.1%)		251/702 (35.8%)
Investigations
Alanine Aminotransferase Increased	29/701 (4.1%)		39/702 (5.6%)
Metabolism and nutrition disorders
Decreased appetite	74/701 (10.6%)		98/702 (14%)
Hypokalaemia	55/701 (7.8%)		67/702 (9.5%)
Musculoskeletal and connective tissue disorders
Back pain	41/701 (5.8%)		58/702 (8.3%)
Arthralgia	28/701 (4%)		37/702 (5.3%)
Nervous system disorders
Dizziness	29/701 (4.1%)		48/702 (6.8%)
Dysgeusia	38/701 (5.4%)		44/702 (6.3%)
Headache	58/701 (8.3%)		75/702 (10.7%)
Neuropathy peripheral	88/701 (12.6%)		87/702 (12.4%)
Paraesthesia	50/701 (7.1%)		55/702 (7.8%)
Peripheral sensory neuropathy	57/701 (8.1%)		54/702 (7.7%)
Psychiatric disorders
Insomnia	61/701 (8.7%)		79/702 (11.3%)
Respiratory, thoracic and mediastinal disorders
Cough	66/701 (9.4%)		88/702 (12.5%)
Dyspnoea	31/701 (4.4%)		52/702 (7.4%)
Oropharyngeal pain	38/701 (5.4%)		43/702 (6.1%)
Skin and subcutaneous tissue disorders
Alopecia	144/701 (20.5%)		148/702 (21.1%)
Rash	45/701 (6.4%)		17/702 (2.4%)
Vascular disorders
Hypertension	27/701 (3.9%)		40/702 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann-La Roche
Phone	800 821-8590
Email	genentech@druginfo.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01287741

Other Study ID Numbers:

BO21005
2010-024194-39

First Posted:

Feb 1, 2011

Last Update Posted:

Apr 12, 2019

Last Verified:

Apr 1, 2019

A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact