A Study of Subcutaneous Versus Intravenous MabThera/Rituxan (Rituximab) in Combination With CHOP Chemotherapy in Patients With Previously Untreated CD20-Positive Diffuse Large B-Cell Lymphoma

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01649856
• Collaborator: (none)
• Enrollment: 572
• Locations: 186
• Arms: 2
• Actual Duration (Months): 48.8
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This multicenter, randomized, open label parallel-group study will evaluate the efficacy and safety of subcutaneous versus intravenous MabThera/Rituxan (rituximab) in combination with CHOP chemotherapy in patients with previously untreated CD20-positive diffuse large B-Cell lymphoma. Patients will be randomized to receive either MabThera/Rituxan 1400 mg subcutaneously or MabThera/Rituxan 375 mg/m2 intravenously on Day 1 of each cycle for 8 cycles, in combination with 6-8 cycles of CHOP chemotherapy. Anticipated time on study treatment is 6 months.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large B-Cell, Diffuse	Drug: CHOP; Drug: rituximab [MabThera/Rituxan]; Drug: rituximab [MabThera/Rituxan]	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 572 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparative, Randomized, Parallel-group, Multi-center, Phase IIIB Study to Investigate the Efficacy of Subcutaneous (SC) Rituximab Versus Intravenous (IV) Rituximab Both in Combination With CHOP (R-CHOP) in Previously Untreated Patients With CD20-positive Diffuse Large B-cell Lymphoma (DLBCL)
• Actual Study Start Date: Aug 24, 2012
• Actual Primary Completion Date: Oct 21, 2014
• Actual Study Completion Date: Sep 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: Rituximab SC	Drug: CHOP; CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles; Drug: rituximab [MabThera/Rituxan]; The first rituximab dose will be administered intravenously on Day of Cycle 1 at a dose of 375 mg/m2. Subsequent doses of 1400 mg are administered subcutaneously on Day 1 of each cycle, for a further 7 cycles
Active Comparator: B: Rituximab IV	Drug: CHOP; CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles; Drug: rituximab [MabThera/Rituxan]; 375 mg/m2 intravenously on Day 1 of each cycle, 8 cycles

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Response (CR) or Complete Response Unconfirmed (CRu) [Up to approximately 4.25 years]

   Tumor response was assessed per criteria published by Cheson et al (1999). According to consensus recommendations, CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by greater than (>) 75 percent (%) but still >1.5 centimeters (cm) in size, and indeterminate bone marrow assessment. The percentage of participants with either response at the end of induction (EOI) was determined with corresponding 95% Pearson-Clopper confidence interval (CI).

Secondary Outcome Measures

1. Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores [At Cycle 7 (each cycle was 14 or 21 days)]

   The CTSQ is a validated 16-item questionnaire that measures three domains related to satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.

2. Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores [At Cycle 7 (each cycle was 14 or 21 days)]

   The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.

3. Median Duration of Rituximab Administration for Each Treatment Cycle [Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)]

   Duration of rituximab administration was defined as the time from start to end of the SC injection or IV infusion. The median duration was reported.

4. Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle [Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)]

   Chair time was defined as the amount of time the participant occupied an infusion chair/bed for a single treatment cycle of rituximab + CHOP chemotherapy. Where the chair time was not documented for a given cycle, it was reported as "Missing".

5. Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle [Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)]

   Hospital time was defined as the amount of time the participant was in the hospital for the course of one cycle of rituximab + CHOP chemotherapy. Where the hospital time was not documented for a given cycle, it was reported as "Missing".

6. Number of Participants With an Event-Free Survival (EFS) Event [Up to approximately 4.25 years]

   EFS events included disease progression, relapse, initiation of other anti-lymphoma therapy, or death. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as greater than or equal to (≥) 50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.

7. Duration of EFS [Up to approximately 4.25 years]

   EFS was defined as the time from randomization to first occurrence of disease progression, relapse, initiation of other anti-lymphoma therapy, or death, whichever occurred first. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as a ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.

8. Number of Participants With Relapse or Death at the Time of Primary Analysis [Up to approximately 2 years (assessed at Baseline, Day 1 of each cycle [maximum 8 cycles; each cycle was 14 or 21 days], every 3 months thereafter, and/or 4 weeks after early termination)]

   Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu. The number of participants who had experienced relapse or death prior to the clinical cut-off date (October 2014) was determined.

9. Duration of Disease-Free Survival (DFS) [Up to approximately 4.25 years]

   DFS was defined as the time from date of initial CR/CRu to the date of relapse or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.

10. Number of Participants With Progression, Relapse, or Death [Up to approximately 4.25 years]

    Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.

11. Duration of Progression-Free Survival (PFS) [Up to approximately 4.25 years]

    PFS was defined as the time from randomization to first occurrence of disease progression, relapse, or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.

12. Number of Deaths [Up to approximately 4.25 years]

13. Duration of Overall Survival (OS) [Up to approximately 4.25 years]

    OS was defined as the time from randomization to death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients, >/= 18 and </= 80 years of age at time of study inclusion

• Histologically confirmed, previously untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) according to the WHO classification system

• Patients with an International Prognostic Index (IPI) score 1-5, or IPI score 0 with bulky disease, defined as one lesion >/= 7.5 cm

• At least one bi-dimensionally measurable lesion defined as >/= 1.5 cm in its largest dimension on CT scan, PET-CT scan or MRI

• Adequate hematologic function

• Eastern Cooperative Oncology Group (EOCD) performance status </= 2

Exclusion Criteria:

• Primary or secondary central nervous system lymphoma, histologic evidence of transformation to Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL, or primary DLBCL of the testis

• Transformed lymphoma or follicular lymphoma IIIB

• Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation

• History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin, carcinoma in situ of the cervix, or a malignancy that has been treated without curative intent and has been in remission without treatment for >/= 5 years prior to enrolment

• Inadequate renal or hepatic function

• Known human immunodeficiency virus (HIV) infection or HIV seropositive status

• Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients with occult or prior HBV infection as defined by protocol may be included. Patients positive for HCV antibody are eligible only if polymerase chain reaction testing for HCV ribonucleic acid is negative.

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products

• Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines

• Prior treatment with cytotoxic drugs or rituximab for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody

• Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	EHS CAC Hospital FRANTZ FANON ZABANA BLIDA; Hematology ward	Blida		Algeria	09000
2	Centre hospitalo-univerisitaire de Tizi Ouzou - Nedir Mohamed;Service d'hématologie	Tizi Ouzou		Algeria	15000
3	Cemic; Haematology	Buenos Aires		Argentina	C1431FWO
4	Hospital Privado de Comunidad; Oncology	Mar Del Plata		Argentina	7600
5	Onze Lieve Vrouwziekenhuis Aalst	Aalst		Belgium	9300
6	ZNA Middelheim	Antwerpen		Belgium	2020
7	CHU Brugmann (Victor Horta)	Bruxelles		Belgium	1020
8	Clin Univ de Bxl Hôpital Erasme	Bruxelles		Belgium	1070
9	CHU Charleroi-ISPPC-Espace Santé	Charleroi		Belgium	6000
10	CHU de Charleroi	Charleroi		Belgium	6000
11	GHdC Site Notre Dame	Charleroi		Belgium	6000
12	UZ Gent	Gent		Belgium	9000
13	Jessa Zkh (Campus Virga Jesse)	Hasselt		Belgium	3500
14	AZ Turnhout Sint Elisabeth	Turnhout		Belgium	2300
15	CHR de Verviers - East Belgium	Verviers		Belgium	4800
16	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE	Brazil	60336-550
17	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ	Brazil	20560-120
18	Clinicas Oncologicas Integradas - COI	Rio De Janeiro	RJ	Brazil	22290-160
19	Hospital Giovanni Battista - Mae de Deus Center; Instituto do Cancer	Porto Alegre	RS	Brazil	90470340
20	Hospital Amaral Carvalho	Jau	SP	Brazil	17210-080
21	Hospital das Clinicas - FMUSP; Hematologia	Sao Paulo	SP	Brazil	05403-000
22	University Hospital Sv.Georgi Clnic of Hematology; Hematology	Plovdiv		Bulgaria	4002
23	Military Medical Academy; Hematology And Oncology	Sofia		Bulgaria	1431
24	UMHAT Alexandrovska EAD; Hematology	Sofia		Bulgaria	1431
25	Lion'S Gate Hospital	North Vancouver	British Columbia	Canada	V7L 2L7
26	Cancer Care Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
27	Regional health authority A vitalite health network	Moncton	New Brunswick	Canada	E1C 8X3
28	Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials	Barrie	Ontario	Canada	L4M 6M2
29	William Osler Health System Brampton Civic Hospital	Brampton	Ontario	Canada	L6R 3J7
30	Grand River Regional Cancer Centre	Kitchener	Ontario	Canada	N2G 1G3
31	Southlake Regional Health Center; Community Care Clinic / Oncology	Newmarket	Ontario	Canada	L3Y 2P9
32	Toronto East General Hospital; Haematology/Oncology	Toronto	Ontario	Canada	M4C 3E7
33	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario	Canada	M5G 2M9
34	Windsor Regional Cancer Centre	Windsor	Ontario	Canada	N8W 2X3
35	Clínica Imbanaco; Oncology	Cali		Colombia
36	Hospital Pablo Tobon Uribe	Medellin-Antioquia		Colombia
37	Helsinki University Central Hospital; Dept of Oncology	Helsinki		Finland	00029
38	Middle Finland Central Hospital	Jyväskylä		Finland	40620
39	Oulu University Hospital; Oncology	Oulu		Finland	90029
40	Tampere University Hospital; Dept of Oncology	Tampere		Finland	33520
41	Turku Uni Central Hospital; Oncology Clinics	Turku		Finland	20520
42	Ch Victor Dupouy; Hematologie	Argenteuil		France	95107
43	Hopital Augustin Morvan; Hematologie	Brest		France	29609
44	Ch Du Mans; Medecine Hematologie Oncologie	Le Mans		France	72037
45	Centre ONCOGARD - Institut de Cancerologie du Gard	Nimes		France	30029
46	Ch De Saint Quentin; Medecine B10	Saint Quentin		France	02321
47	Hopital Sud; Hematologie Clinique	Salouel		France	80480
48	Hopital Yves Le Foll; Hematologie Oncologie	St Brieuc		France	22027
49	Clinique Ste Anne	Strasbourg		France	67000
50	Hopital Hautepierre; Hematologie Oncologie	Strasbourg		France	67098
51	Hia Sainte Anne; Medecine Interne Oncologie	Toulon		France	83041
52	University General Hospital of Alexandroupolis; Haemotology	Alexandroupolis		Greece	68100
53	General Hospital of Athens Evangelismos; Hematology	Athens		Greece	106 76
54	Laiko General Hospital; Hematology Clinic	Athens		Greece	115 27
55	Metropolitan Hospital; Hematology Dept	Athens		Greece	18547
56	Periph. University General Hospital of Heraklion; Hematology	Heraklion		Greece	711 10
57	University Hospital of Ioannina; Hematology	Ioannina		Greece	455 00
58	University Hospital Of Patras; Dept. Of Internal Medicine-Hematology Division	Patras		Greece	265 00
59	Theagenio Anticancer Hospital; Dept. of Haematology	Thessaloniki		Greece	54007
60	Georgios Papanikolaou Hospital; Hematology Department	Thessaloniki		Greece	570 10
61	Cork Uni Hospital; Oncology Dept	Cork		Ireland
62	Mater Misericordiae Uni Hospital; Oncology	Dublin		Ireland	7
63	St James' Hospital; Cancer Clinical Trials Office	Dublin		Ireland
64	Galway Uni Hospital; Oncology Dept	Galway		Ireland
65	University Hospital Limerick - Oncology	Limerick		Ireland
66	Haemek Medical Center; Hematology Department	Afula		Israel	18101
67	Rambam Medical Center; Heamatology & Bone Marrow Transplantation	Haifa		Israel	3109601
68	Wolfson Mc; Haematology	Holon		Israel	5810001
69	Shaare Zedek Medical Center; Hematology Dept.	Jerusalem		Israel	9103102
70	Meir Medical Center; Heamatology Dept	Kfar Saba		Israel	4428164
71	Beilinson Medical Center; Haematology	Petach Tikva		Israel	49100
72	Chaim Sheba Medical Center; Hematology BMT & CBB	Ramat Gan		Israel	52662
73	Kaplan Medical Center	Rehovot		Israel	7661041
74	Ichilov Sourasky Medical Center; Heamatology	Tel Aviv		Israel	6423906
75	Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia	Pescara	Abruzzo	Italy	65100
76	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna	Italy	47014
77	Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia	Ravenna	Emilia-Romagna	Italy	48100
78	Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia	Rimini	Emilia-Romagna	Italy	47900
79	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia	Italy	33081
80	AOU Ospedali Riuniti; Ematologia	Trieste	Friuli-Venezia Giulia	Italy	34125
81	Uni Cattolica; Divisione Di Ematologia	Roma	Lazio	Italy	00168
82	Az. Osp. Sant'Andrea; U.O. C. Ematologia	Roma	Lazio	Italy	00189
83	ASST PAPA GIOVANNI XXIII; Ematologia	Bergamo	Lombardia	Italy	24127
84	ASST DI CREMONA; U.O.S. di Ematologia	Cremona	Lombardia	Italy	26100
85	Ospedale Di Circolo E Fondazione Macchi; Ematologia	Varese	Lombardia	Italy	21100
86	Ospedale Civile; S.C. Ematologia	Pesaro	Marche	Italy	61100
87	A.O. Univ.Ospedali Riuniti Umerto I -G.M.Lancisi G.Salesi; U.O. Clinica Di Ematologia	Torrette Di Ancona	Marche	Italy	60020
88	Ospedale Mauriziano Umberto I	Torino	Piemonte	Italy	10128
89	Az. Osp. G. Moscati; U.O. Do Ematologia	Taranto	Puglia	Italy	74100
90	Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.	Cagliari	Sardegna	Italy	09121
91	Azienda Ospedaliero Uni Ria Policlinico G. Martino; U.O. Di Oncologia Medica	Messina	Sicilia	Italy	98123
92	Casa Di Cura La Maddalena; Oncoematologia E Trapianto Del Midollo Osseo	Palermo	Sicilia	Italy	90146
93	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria	Italy	06156
94	Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia	Padova	Veneto	Italy	35128
95	Medisch Centrum Alkmaar	Alkmaar		Netherlands	1815 JD
96	Meander Medisch Centrum; Locatie Lichtenberg	Amersfoort		Netherlands	3818 ES
97	Deventer Ziekenhuis; Interne Geneeskunde	Deventer		Netherlands	7416 SE
98	Albert Schweitzer Ziekenhuis	Dordrecht		Netherlands	3371 NM
99	Maxima Medisch Centrum; Inwendige Geneeskunde	Eindhoven		Netherlands	5631 BM
100	Groene Hart Ziekenhuis Bleulandlocatie; Inwendige Geneeskunde	Gouda		Netherlands	2803 HH
101	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9700 RB
102	Atrium Medisch Centrum	Heerlen		Netherlands	6419 PC
103	Spaarne Ziekenhuis; Inwendige Geneeskunde	Hoofddorp		Netherlands	2134 TM
104	Medisch Centrum Leeuwarden; Interne	Leeuwarden		Netherlands	8934 AD
105	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein		Netherlands	3430 EM
106	Erasmus Mc - Locatie Centrum; Dept of Hematology	Rotterdam		Netherlands	3015 CE
107	Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed	Rotterdam		Netherlands	3075EA
108	Maasstad ziekenhuis	Rotterdam		Netherlands	3078 HT
109	Zuyderland ziekenhuis locatie Geleen	Sittard-Geleen		Netherlands	6162 BG
110	Isala Klinieken, Locatie Sophia; Inwendige Geneeskunde	Zwolle		Netherlands	8025 AB
111	Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica	Chiclayo		Peru	CIX
112	Instituto;Oncologico Miraflores	Lima		Peru	18
113	Oncosalud Sac; Oncología	Lima		Peru	41
114	Katedra i Klinika Hematologii i Transplantacji Szpiku SUM	Katowice		Poland	40-032
115	Swietokrzyskie Centrum Onkologii; Onkologia Ogolna	Kielce		Poland	25-734
116	Malopolskie Centrum Medyczne	Krakow		Poland	30-510
117	Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej	Opole		Poland	45-061
118	Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny	Slupsk		Poland	76-200
119	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego	Warszawa		Poland	02-781
120	HUC; Servico de Hematologia	Coimbra		Portugal	3000-075
121	Hospital Santo Antonio dos Capuchos; Servico de Hemato-Oncologia	Lisboa		Portugal	1150-314
122	Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula	Lisboa		Portugal	1600
123	IPO do Porto; Servico de Onco-Hematologia	Porto		Portugal	4200-072
124	Hospital de Sao Joao; Servico de Hematologia Clinica	Porto		Portugal	4200-319
125	Regional Oncology Center	Chelyabinsk		Russian Federation	454087
126	Central City Hospital #7; Hematology	Ekaterinburg		Russian Federation	620137
127	Republican Clinical Oncologic Dispensary of Republic Of Tatarstan	Kazan		Russian Federation	420029
128	N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis	Moscow		Russian Federation	115478
129	Rus Med Academy for Postgraduate Education; Oncology Department	Moscow		Russian Federation	123995
130	Vladimirskiy Regional Scientific Research Inst. ; Hematology	Moscow		Russian Federation	129110
131	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod		Russian Federation	603126
132	Clinical MSCh No1	Perm		Russian Federation	614077
133	City Clinical Hospital #15; Hematology department	Saint-Petersburg		Russian Federation	198205
134	Saint-Petersburg SHI City Clinical Hospital #31	St. Petersburg		Russian Federation	197110
135	Riyadh Military Hospital	Riyadh		Saudi Arabia	11159
136	Clinical Center Kragujevac;Center for Hematology	Kragujevac		Serbia	34000
137	Clinic of Haematology Cc Nis	NIS		Serbia	18000
138	National Hospital; Oncotherapy Dept	Bloemfontein		South Africa	9301
139	Tygerberg Hospital; Haematology Department	Cape Town		South Africa	7505
140	Steve Biko Academic Hospital; Oncology	Pretoria		South Africa	0002
141	Hospital de Cabueñes; Servicio de Hematología y Hemoterapia	Gijon	Asturias	Spain	33203
142	Corporacio Sanitaria Parc Tauli; Servicio de Hematologia	Sabadell	Barcelona	Spain	08208
143	Hospital Punta Europa; Servicio de Hematologia	Algeciras	Cadiz	Spain	11207
144	Hospital Universitario Marques de Valdecilla; Servicio de Hematologia	Santander	Cantabria	Spain	39008
145	Hospital de Donostia; Servicio de Hematologia	San Sebastian	Guipuzcoa	Spain	20014
146	Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Hematologia	Las Palmas de Gran Canarias	Las Palmas	Spain	35016
147	Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia	Las Palmas de Gran Canaria	Las Palmas	Spain	35020
148	Hospital de Cruces; Servicio de Hematologia	Barakaldo	Vizcaya	Spain	48903
149	Hospital General Univ. de Alicante; Servicio de Oncologia	Alicante		Spain	3010
150	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Hematologia	Girona		Spain	17007
151	Hospital Lucus Augusti; Servicio de Hematologia	Lugo		Spain	27003
152	Hospital General Universitario Gregorio Marañon; Servicio de Hematología	Madrid		Spain	28007
153	Hospital Univ. 12 de Octubre; Servicio de Hematologia	Madrid		Spain	28041
154	Hospital Universitario la Paz; Servicio de Hematologia	Madrid		Spain	28046
155	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Madrid		Spain	28222
156	Hospital Costa del Sol; Servicio de Hematologia	Malaga		Spain	29600
157	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia		Spain	46010
158	Hospital Universitario Dr. Peset; Servicio de Hematologia	Valencia		Spain	46017
159	Hospital Clinico Universitario Lozano Blesa; Servicio de Hematologia	Zaragoza		Spain	50009
160	Hospital Universitario Miguel Servet; Servicio Hematologia	Zaragoza		Spain	50009
161	King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10330
162	Ramathibodi Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10400
163	Siriraj Hospital; Division of Hematology, Department of Medicine	Bangkok		Thailand	10700
164	Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine	Khon Kaen		Thailand	40002
165	Cukurova Uni ; Hematology	Adana		Turkey	01330
166	Diskapi Research And Training Hospital; hematology	Ankara		Turkey	06000
167	Hacettepe Uni Medical Faculty; Hematology	Ankara		Turkey	06100
168	Ankara University; Hematology	Ankara		Turkey	06620
169	Gaziantep Uni Medical School; Hematology	Gaziantep		Turkey	27310
170	Istanbul University Cerrahpasa Medical Faculty; Hematology Department	Istanbul		Turkey	34098
171	Dokuz Eylul Uni ; Hematology	Izmir		Turkey	35100
172	Ege Uni Medical School; Hematology	Izmir		Turkey	35100
173	Erciyes Uni ; Hematology	Kayseri		Turkey	38039
174	Ondokuzmayis University Medical Faculty Heamatology Department	Samsun		Turkey	55139
175	Cumhuriyet Uni. Med. Fac.; Hematology	Sivas		Turkey	58140
176	Karadeniz Technical Uni School of Medicine; Hematology	Trabzon		Turkey	61800
177	Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU; Chair of Oncology and Medical Radiology	Dnipropetrovsk		Ukraine	49102
178	Kyiv City Clinical Oncological Center; Chemotherapy Department	Kiev		Ukraine	03115
179	State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department	Lviv		Ukraine	79031
180	SOUTHMEAD HOSPITAL; Richard Bright Dialysis Centre	Bristol		United Kingdom	BS10 5NB
181	Ipswich Hospital; Oncology Pharmacy	Ipswich		United Kingdom	IP4 5PD
182	Macclesfield District General Hospital	Macclesfield		United Kingdom	SK10 3BL
183	Kings Mill Hospital	Sutton in Ashfield		United Kingdom	NG17 4JL
184	Singleton Hospital: Pharmacy Department	Swansea		United Kingdom	SA2 8QA
185	Instituto de Oncologia y Hematologia UCV	Caracas		Venezuela	1020
186	Banco Municipal de Sangre; Hematología	Caracas		Venezuela	2122

Sponsors and Collaborators

• Hoffmann-La Roche

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: NCT01649856
• Other Study ID Numbers: MO28107; 2012-000669-19
• First Posted: Jul 25, 2012
• Last Update Posted: Oct 11, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Rituximab

Study Results

Participant Flow

Pre-assignment Detail	A total of 662 individuals were screened for entry into the study, and 86 failed the screening procedure. Overall, 576 participants were randomized; 572 received treatment and were included in the analyses.

Arm/Group Title	Rituximab Subcutaneous (SC)	Rituximab Intravenous (IV)
Arm/Group Description	Participants with previously untreated, cluster of differentiation (CD) 20-positive diffuse large B-cell lymphoma (DLBCL) received up to 8 cycles of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 milligrams per meter-squared (mg/m^2) via IV infusion; subsequent doses were given as 1400 milligrams (mg) via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved complete response (CR) or complete response unconfirmed (CRu) after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Period Title: Overall Study
STARTED	369	203
COMPLETED	230	125
NOT COMPLETED	139	78

Baseline Characteristics

Arm/Group Title	Rituximab SC	Rituximab IV	Total
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Total of all reporting groups
Overall Participants	369	203	572
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (13.78)	61.0 (12.63)	60.6 (13.38)
Sex: Female, Male (Count of Participants)
Female	165 44.7%	100 49.3%	265 46.3%
Male	204 55.3%	103 50.7%	307 53.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response (CR) or Complete Response Unconfirmed (CRu)
Description	Tumor response was assessed per criteria published by Cheson et al (1999). According to consensus recommendations, CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by greater than (>) 75 percent (%) but still >1.5 centimeters (cm) in size, and indeterminate bone marrow assessment. The percentage of participants with either response at the end of induction (EOI) was determined with corresponding 95% Pearson-Clopper confidence interval (CI).
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants who completed Baseline and at least one on-treatment efficacy assessment.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Number (95% Confidence Interval) [percentage of participants]	50.6 13.7%	42.4 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab SC, Rituximab IV
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.076
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	8.2
	Confidence Interval	() 95%; -1.1 to 17.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores
Description	The CTSQ is a validated 16-item questionnaire that measures three domains related to satisfaction with cancer therapy. These include expectations of therapy, feelings about side effects, and satisfaction with therapy. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.
Time Frame	At Cycle 7 (each cycle was 14 or 21 days)

Outcome Measure Data

Analysis Population Description

ITT Population (CTSQ Subpopulation): All participants who completed the CTSQ at Cycles 3 and 7; number (n) = number of participants in the analysis for the specified domain.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	280	141
Expectations of Therapy (n=280,141)	79.35 (17.422)	82.94 (16.536)
Feelings about Side Effects (n=276,141)	60.69 (21.594)	57.62 (23.339)
Satisfaction with Therapy (n=278,141)	85.92 (11.428)	83.60 (13.451)

3. Secondary Outcome

Title	Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores
Description	The RASQ is a 20-item questionnaire that measures five domains related to the impact of treatment administration. These include physical impact, psychological impact, impact on activities of daily living (ADLs), convenience, and satisfaction. Each domain is scored on a scale of 0 to 100, with higher scores indicative of more positive feelings toward therapy. The score for each domain was averaged among all participants.
Time Frame	At Cycle 7 (each cycle was 14 or 21 days)

Outcome Measure Data

Analysis Population Description

ITT Population (RASQ Subpopulation): All participants who completed the RASQ at Cycles 3 and 7; n = number of participants in the analysis for the specified domain.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	284	144
Physical Impact (n=278,140)	86.24 (14.012)	81.49 (16.848)
Psychological Impact (n=277,141)	85.65 (13.920)	78.65 (18.233)
Impact on ADLs (n=266,140)	83.77 (16.117)	57.38 (19.230)
Convenience (n=279,143)	82.32 (13.428)	60.14 (17.473)
Satisfaction (n=282,141)	89.58 (12.051)	77.39 (18.232)

4. Secondary Outcome

Title	Median Duration of Rituximab Administration for Each Treatment Cycle
Description	Duration of rituximab administration was defined as the time from start to end of the SC injection or IV infusion. The median duration was reported.
Time Frame	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)

Outcome Measure Data

Analysis Population Description

Safety Population; n = number of participants in the analysis for the specified timepoint.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	369	203
Cycle 1 (n=346,190)	4.0	4.0
Cycle 2 (n=361,178)	0.1	3.0
Cycle 3 (n=349,177)	0.1	2.8
Cycle 4 (n=346,173)	0.1	2.7
Cycle 5 (n=332,165)	0.1	2.6
Cycle 6 (n=319,162)	0.1	2.7
Cycle 7 (n=304,156)	0.1	2.7
Cycle 8 (n=305,152)	0.1	2.55
Overall (n=368,201)	4.7	19.00

5. Secondary Outcome

Title	Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle
Description	Chair time was defined as the amount of time the participant occupied an infusion chair/bed for a single treatment cycle of rituximab + CHOP chemotherapy. Where the chair time was not documented for a given cycle, it was reported as "Missing".
Time Frame	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	369	203
Less than 30 minutes (Cycle 1)	0 0%	0 0%
30 minutes to 1 hour (Cycle 1)	0 0%	0.5 0.2%
1 to 2 hours (Cycle 1)	1.4 0.4%	0 0%
2 to 4 hours (Cycle 1)	20.6 5.6%	17.2 8.5%
4 to 12 hours (Cycle 1)	69.4 18.8%	72.4 35.7%
More than 12 hours (Cycle 1)	7.3 2%	7.9 3.9%
Missing (Cycle 1)	1.4 0.4%	2.0 1%
Less than 30 minutes (Cycle 2)	7.3 2%	0 0%
30 minutes to 1 hour (Cycle 2)	2.4 0.7%	0 0%
1 to 2 hours (Cycle 2)	17.1 4.6%	1.1 0.5%
2 to 4 hours (Cycle 2)	56.1 15.2%	36.2 17.8%
4 to 12 hours (Cycle 2)	12.2 3.3%	60.1 29.6%
More than 12 hours (Cycle 2)	0.3 0.1%	1.1 0.5%
Missing (Cycle 2)	4.6 1.2%	1.6 0.8%
Less than 30 minutes (Cycle 3)	5.6 1.5%	0 0%
30 minutes to 1 hour (Cycle 3)	2.0 0.5%	0 0%
1 to 2 hours (Cycle 3)	22.1 6%	0.5 0.2%
2 to 4 hours (Cycle 3)	55.9 15.1%	38.9 19.2%
4 to 12 hours (Cycle 3)	12.6 3.4%	58.4 28.8%
More than 12 hours (Cycle 3)	0.3 0.1%	0.5 0.2%
Missing (Cycle 3)	1.7 0.5%	1.6 0.8%
Less than 30 minutes (Cycle 4)	5.1 1.4%	0 0%
30 minutes to 1 hour (Cycle 4)	2.8 0.8%	0 0%
1 to 2 hours (Cycle 4)	21.8 5.9%	1.1 0.5%
2 to 4 hours (Cycle 4)	55.0 14.9%	36.7 18.1%
4 to 12 hours (Cycle 4)	13.9 3.8%	60.6 29.9%
More than 12 hours (Cycle 4)	0.3 0.1%	0.6 0.3%
Missing (Cycle 4)	1.1 0.3%	1.1 0.5%
Less than 30 minutes (Cycle 5)	5.0 1.4%	0.6 0.3%
30 minutes to 1 hour (Cycle 5)	2.4 0.7%	0 0%
1 to 2 hours (Cycle 5)	25.2 6.8%	1.1 0.5%
2 to 4 hours (Cycle 5)	53.4 14.5%	40.2 19.8%
4 to 12 hours (Cycle 5)	12.8 3.5%	56.3 27.7%
More than 12 hours (Cycle 5)	0 0%	0.6 0.3%
Missing (Cycle 5)	1.2 0.3%	1.1 0.5%
Less than 30 minutes (Cycle 6)	3.4 0.9%	0.6 0.3%
30 minutes to 1 hour (Cycle 6)	3.1 0.8%	0 0%
1 to 2 hours (Cycle 6)	23.0 6.2%	1.8 0.9%
2 to 4 hours (Cycle 6)	56.7 15.4%	42.5 20.9%
4 to 12 hours (Cycle 6)	12.3 3.3%	53.3 26.3%
More than 12 hours (Cycle 6)	0 0%	0 0%
Missing (Cycle 6)	1.5 0.4%	1.8 0.9%
Less than 30 minutes (Cycle 7)	18.7 5.1%	0 0%
30 minutes to 1 hour (Cycle 7)	7.0 1.9%	0 0%
1 to 2 hours (Cycle 7)	26.9 7.3%	4.9 2.4%
2 to 4 hours (Cycle 7)	40.2 10.9%	48.8 24%
4 to 12 hours (Cycle 7)	6.0 1.6%	44.4 21.9%
More than 12 hours (Cycle 7)	0 0%	0 0%
Missing (Cycle 7)	1.3 0.4%	1.9 0.9%
Less than 30 minutes (Cycle 8)	20.3 5.5%	0.6 0.3%
30 minutes to 1 hour (Cycle 8)	6.4 1.7%	0 0%
1 to 2 hours (Cycle 8)	29.3 7.9%	4.4 2.2%
2 to 4 hours (Cycle 8)	36.7 9.9%	50.9 25.1%
4 to 12 hours (Cycle 8)	5.8 1.6%	43.4 21.4%
More than 12 hours (Cycle 8)	0 0%	0 0%
Missing (Cycle 8)	1.6 0.4%	0.6 0.3%

6. Secondary Outcome

Title	Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle
Description	Hospital time was defined as the amount of time the participant was in the hospital for the course of one cycle of rituximab + CHOP chemotherapy. Where the hospital time was not documented for a given cycle, it was reported as "Missing".
Time Frame	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	369	203
Less than 2 hours (Cycle 1)	0.3 0.1%	0 0%
2 to 4 hours (Cycle 1)	3.0 0.8%	1.5 0.7%
4 to 6 hours (Cycle 1)	19.8 5.4%	20.7 10.2%
6 to 12 hours (Cycle 1)	39.0 10.6%	43.8 21.6%
12 to 24 hours (Cycle 1)	8.9 2.4%	6.9 3.4%
More than 24 hours (Cycle 1)	26.8 7.3%	24.1 11.9%
Missing (Cycle 1)	2.2 0.6%	3.0 1.5%
Less than 2 hours (Cycle 2)	3.8 1%	0 0%
2 to 4 hours (Cycle 2)	33.1 9%	10.1 5%
4 to 6 hours (Cycle 2)	27.9 7.6%	33.5 16.5%
6 to 12 hours (Cycle 2)	16.3 4.4%	38.8 19.1%
12 to 24 hours (Cycle 2)	3.8 1%	1.1 0.5%
More than 24 hours (Cycle 2)	10.3 2.8%	11.7 5.8%
Missing (Cycle 2)	4.9 1.3%	4.8 2.4%
Less Than 2 hours (Cycle 3)	3.6 1%	0.5 0.2%
2 to 4 hours (Cycle 3)	37.2 10.1%	11.9 5.9%
4 to 6 hours (Cycle 3)	30.2 8.2%	30.8 15.2%
6 to 12 hours (Cycle 3)	14.5 3.9%	41.6 20.5%
12 to 24 hours (Cycle 3)	2.8 0.8%	2.2 1.1%
More than 24 hours (Cycle 3)	9.8 2.7%	10.3 5.1%
Missing (Cycle 3)	2.0 0.5%	2.7 1.3%
Less Than 2 hours (Cycle 4)	4.5 1.2%	0 0%
2 to 4 hours (Cycle 4)	36.3 9.8%	10.0 4.9%
4 to 6 hours (Cycle 4)	27.5 7.5%	31.1 15.3%
6 to 12 hours (Cycle 4)	17.6 4.8%	42.2 20.8%
12 to 24 hours (Cycle 4)	2.0 0.5%	2.8 1.4%
More than 24 hours (Cycle 4)	10.2 2.8%	10.6 5.2%
Missing (Cycle 4)	2.0 0.5%	3.3 1.6%
Less Than 2 hours (Cycle 5)	5.0 1.4%	0.6 0.3%
2 to 4 hours (Cycle 5)	39.5 10.7%	11.5 5.7%
4 to 6 hours (Cycle 5)	26.4 7.2%	34.5 17%
6 to 12 hours (Cycle 5)	16.0 4.3%	37.4 18.4%
12 to 24 hours (Cycle 5)	2.1 0.6%	1.7 0.8%
More than 24 hours (Cycle 5)	8.9 2.4%	10.9 5.4%
Missing (Cycle 5)	2.1 0.6%	3.4 1.7%
Less Than 2 hours (Cycle 6)	4.3 1.2%	0.6 0.3%
2 to 4 hours (Cycle 6)	39.6 10.7%	12.6 6.2%
4 to 6 hours (Cycle 6)	26.4 7.2%	34.1 16.8%
6 to 12 hours (Cycle 6)	16.3 4.4%	38.3 18.9%
12 to 24 hours (Cycle 6)	2.5 0.7%	2.4 1.2%
More than 24 hours (Cycle 6)	8.6 2.3%	9.0 4.4%
Missing (Cycle 6)	2.5 0.7%	3.0 1.5%
Less Than 2 hours (Cycle 7)	17.7 4.8%	0 0%
2 to 4 hours (Cycle 7)	40.8 11.1%	23.5 11.6%
4 to 6 hours (Cycle 7)	19.9 5.4%	36.4 17.9%
6 to 12 hours (Cycle 7)	10.4 2.8%	30.9 15.2%
12 to 24 hours (Cycle 7)	2.8 0.8%	2.5 1.2%
More than 24 hours (Cycle 7)	5.7 1.5%	3.7 1.8%
Missing (Cycle 7)	2.5 0.7%	3.1 1.5%
Less Than 2 hours (Cycle 8)	18.0 4.9%	0 0%
2 to 4 hours (Cycle 8)	40.5 11%	25.8 12.7%
4 to 6 hours (Cycle 8)	21.9 5.9%	34.0 16.7%
6 to 12 hours (Cycle 8)	8.7 2.4%	30.8 15.2%
12 to 24 hours (Cycle 8)	2.6 0.7%	1.3 0.6%
More than 24 hours (Cycle 8)	5.8 1.6%	5.0 2.5%
Missing (Cycle 8)	2.6 0.7%	3.1 1.5%

7. Secondary Outcome

Title	Number of Participants With an Event-Free Survival (EFS) Event
Description	EFS events included disease progression, relapse, initiation of other anti-lymphoma therapy, or death. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as greater than or equal to (≥) 50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Number [participants]	116 31.4%	53 26.1%

8. Secondary Outcome

Title	Duration of EFS
Description	EFS was defined as the time from randomization to first occurrence of disease progression, relapse, initiation of other anti-lymphoma therapy, or death, whichever occurred first. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as a ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Median (Full Range) [months]	NA	NA

9. Secondary Outcome

Title	Number of Participants With Relapse or Death at the Time of Primary Analysis
Description	Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu. The number of participants who had experienced relapse or death prior to the clinical cut-off date (October 2014) was determined.
Time Frame	Up to approximately 2 years (assessed at Baseline, Day 1 of each cycle [maximum 8 cycles; each cycle was 14 or 21 days], every 3 months thereafter, and/or 4 weeks after early termination)

Outcome Measure Data

Analysis Population Description

ITT Population (Responder Subpopulation): All participants who achieved CR or CRu after 4 cycles.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	178	90
Number [participants]	12 3.3%	5 2.5%

10. Secondary Outcome

Title	Duration of Disease-Free Survival (DFS)
Description	DFS was defined as the time from date of initial CR/CRu to the date of relapse or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population (Responder Subpopulation).

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	240	118
Median (Full Range) [months]	NA	NA

11. Secondary Outcome

Title	Number of Participants With Progression, Relapse, or Death
Description	Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Number [participants]	95 25.7%	38 18.7%

12. Secondary Outcome

Title	Duration of Progression-Free Survival (PFS)
Description	PFS was defined as the time from randomization to first occurrence of disease progression, relapse, or death from any cause. Tumor response was assessed according to criteria published by Cheson et al (1999). Progression was defined as ≥50% increase in the sum of products of greatest diameters of any previously identified abnormal lymph node or the appearance of any new lesion. Relapse was defined as a new lesion or increase by ≥50% in size of previously involved sites, or ≥50% increase in greatest diameter of any previously identified node >1 cm, following an earlier assessment of CR or CRu.
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Median (Full Range) [months]	NA	NA

13. Secondary Outcome

Title	Number of Deaths
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Number [participants]	56 15.2%	22 10.8%

14. Secondary Outcome

Title	Duration of Overall Survival (OS)
Description	OS was defined as the time from randomization to death from any cause.
Time Frame	Up to approximately 4.25 years

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Rituximab SC	Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
Measure Participants	342	177
Median (Full Range) [months]	NA	NA

Adverse Events

Time Frame	Up to approximately 4.25 years
Adverse Event Reporting Description	Safety Population.
Arm/Group Title	Rituximab SC		Rituximab IV
Arm/Group Description	Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For Cycle 1, rituximab was administered at a dose of 375 mg/m^2 via IV infusion; subsequent doses were given as 1400 mg via SC injection. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.		Participants with previously untreated, CD20-positive DLBCL received up to 8 cycles of rituximab in combination with CHOP. Treatment was given on Day 1 of each cycle, and the cycle length (14 or 21 days) was decided by the study center. For all cycles, rituximab was administered at a dose of 375 mg/m^2 via IV infusion. Tumor response was assessed after 4 cycles according to criteria published by Cheson et al (1999), which are presented in Outcome Measure 1. The duration of CHOP therapy could be reduced from 8 to 6 cycles for those who achieved CR or CRu after 4 cycles, but all participants received a full 8 cycles of rituximab.
All Cause Mortality
	Rituximab SC		Rituximab IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rituximab SC		Rituximab IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	155/369 (42%)		77/203 (37.9%)
Blood and lymphatic system disorders
Febrile neutropenia	49/369 (13.3%)		24/203 (11.8%)
Neutropenia	22/369 (6%)		10/203 (4.9%)
Anaemia	2/369 (0.5%)		2/203 (1%)
Leukopenia	1/369 (0.3%)		3/203 (1.5%)
Febrile bone marrow aplasia	0/369 (0%)		1/203 (0.5%)
Pancytopenia	1/369 (0.3%)		0/203 (0%)
Cardiac disorders
Atrial fibrillation	2/369 (0.5%)		3/203 (1.5%)
Cardiac arrest	1/369 (0.3%)		3/203 (1.5%)
Atrial flutter	1/369 (0.3%)		1/203 (0.5%)
Myocardial infarction	0/369 (0%)		2/203 (1%)
Tachycardia	1/369 (0.3%)		1/203 (0.5%)
Acute myocardial infarction	1/369 (0.3%)		0/203 (0%)
Cardiac failure	1/369 (0.3%)		0/203 (0%)
Cardiac failure acute	1/369 (0.3%)		0/203 (0%)
Congestive cardiomyopathy	1/369 (0.3%)		0/203 (0%)
Left ventricular failure	1/369 (0.3%)		0/203 (0%)
Sinus tachycardia	0/369 (0%)		1/203 (0.5%)
Supraventricular tachycardia	1/369 (0.3%)		0/203 (0%)
Tachycardia induced cardiomyopathy	1/369 (0.3%)		0/203 (0%)
Cardiac failure congestive	1/369 (0.3%)		1/203 (0.5%)
Acute coronary syndrome	0/369 (0%)		1/203 (0.5%)
Gastrointestinal disorders
Abdominal pain	3/369 (0.8%)		1/203 (0.5%)
Diarrhoea	2/369 (0.5%)		0/203 (0%)
Vomiting	3/369 (0.8%)		0/203 (0%)
Nausea	1/369 (0.3%)		1/203 (0.5%)
Abdominal distension	1/369 (0.3%)		0/203 (0%)
Anal fissure	1/369 (0.3%)		0/203 (0%)
Anal haemorrhage	1/369 (0.3%)		0/203 (0%)
Constipation	0/369 (0%)		1/203 (0.5%)
Gastric perforation	0/369 (0%)		1/203 (0.5%)
Gastrointestinal haemorrhage	1/369 (0.3%)		0/203 (0%)
Haematemesis	1/369 (0.3%)		0/203 (0%)
Haemorrhoidal haemorrhage	1/369 (0.3%)		0/203 (0%)
Ileus	2/369 (0.5%)		0/203 (0%)
Intestinal obstruction	1/369 (0.3%)		0/203 (0%)
Large intestine perforation	1/369 (0.3%)		0/203 (0%)
Neutropenic colitis	1/369 (0.3%)		0/203 (0%)
Obstruction gastric	1/369 (0.3%)		0/203 (0%)
Pancreatitis	1/369 (0.3%)		0/203 (0%)
Upper gastrointestinal haemorrhage	2/369 (0.5%)		0/203 (0%)
Inguinal hernia	0/369 (0%)		1/203 (0.5%)
Small intestinal perforation	1/369 (0.3%)		0/203 (0%)
General disorders
Pyrexia	7/369 (1.9%)		3/203 (1.5%)
Chills	2/369 (0.5%)		2/203 (1%)
Chest pain	0/369 (0%)		1/203 (0.5%)
Death	2/369 (0.5%)		0/203 (0%)
Fatigue	0/369 (0%)		1/203 (0.5%)
General physical health deterioration	1/369 (0.3%)		0/203 (0%)
Influenza like illness	0/369 (0%)		1/203 (0.5%)
Injection site hypertrophy	1/369 (0.3%)		0/203 (0%)
Localised oedema	0/369 (0%)		1/203 (0.5%)
Mucosal inflammation	1/369 (0.3%)		0/203 (0%)
Oedema peripheral	1/369 (0.3%)		0/203 (0%)
Sudden death	0/369 (0%)		1/203 (0.5%)
Ill-defined disorder	1/369 (0.3%)		0/203 (0%)
Hepatobiliary disorders
Bile duct obstruction	1/369 (0.3%)		0/203 (0%)
Cholecystitis	0/369 (0%)		1/203 (0.5%)
Hepatic failure	1/369 (0.3%)		0/203 (0%)
Immune system disorders
Cytokine release syndrome	0/369 (0%)		1/203 (0.5%)
Infections and infestations
Pneumonia	27/369 (7.3%)		7/203 (3.4%)
Septic shock	3/369 (0.8%)		3/203 (1.5%)
Lung infection	4/369 (1.1%)		1/203 (0.5%)
Respiratory tract infection	2/369 (0.5%)		0/203 (0%)
Sepsis	5/369 (1.4%)		0/203 (0%)
Cellulitis	2/369 (0.5%)		0/203 (0%)
Infection	2/369 (0.5%)		0/203 (0%)
Lower respiratory tract infection	1/369 (0.3%)		1/203 (0.5%)
Urosepsis	1/369 (0.3%)		1/203 (0.5%)
Anal abscess	1/369 (0.3%)		0/203 (0%)
Appendicitis	2/369 (0.5%)		0/203 (0%)
Bronchiolitis	1/369 (0.3%)		0/203 (0%)
Bronchitis	1/369 (0.3%)		0/203 (0%)
Clostridium difficile colitis	1/369 (0.3%)		0/203 (0%)
Erysipelas	1/369 (0.3%)		0/203 (0%)
Gastroenteritis	1/369 (0.3%)		0/203 (0%)
H1N1 influenza	1/369 (0.3%)		0/203 (0%)
Herpes oesophagitis	1/369 (0.3%)		0/203 (0%)
Herpes simplex hepatitis	1/369 (0.3%)		0/203 (0%)
Herpes zoster	2/369 (0.5%)		0/203 (0%)
Klebsiella sepsis	1/369 (0.3%)		0/203 (0%)
Neutropenic infection	1/369 (0.3%)		0/203 (0%)
Oral candidiasis	1/369 (0.3%)		0/203 (0%)
Oral herpes	1/369 (0.3%)		0/203 (0%)
Peritonitis	1/369 (0.3%)		0/203 (0%)
Pneumocystis jirovecii infection	0/369 (0%)		1/203 (0.5%)
Pneumocystis jirovecii pneumonia	1/369 (0.3%)		0/203 (0%)
Sinusitis	0/369 (0%)		1/203 (0.5%)
Tuberculosis	0/369 (0%)		1/203 (0.5%)
Upper respiratory tract infection	1/369 (0.3%)		0/203 (0%)
Urinary tract infection	1/369 (0.3%)		1/203 (0.5%)
Viral infection	0/369 (0%)		1/203 (0.5%)
Viral upper respiratory tract infection	1/369 (0.3%)		0/203 (0%)
Gastroenteritis norovirus	1/369 (0.3%)		0/203 (0%)
Intervertebral discitis	1/369 (0.3%)		0/203 (0%)
Localised infection	1/369 (0.3%)		0/203 (0%)
Lower respiratory tract infection viral	1/369 (0.3%)		1/203 (0.5%)
Pneumonia cytomegaloviral	1/369 (0.3%)		0/203 (0%)
Injury, poisoning and procedural complications
Multiple fractures	2/369 (0.5%)		0/203 (0%)
Femur fracture	2/369 (0.5%)		0/203 (0%)
Fracture	0/369 (0%)		1/203 (0.5%)
Hip fracture	0/369 (0%)		1/203 (0.5%)
Infusion related reaction	0/369 (0%)		1/203 (0.5%)
Lower limb fracture	1/369 (0.3%)		0/203 (0%)
Subdural haematoma	0/369 (0%)		1/203 (0.5%)
Transfusion reaction	0/369 (0%)		1/203 (0.5%)
Procedural pneumothorax	1/369 (0.3%)		0/203 (0%)
Investigations
Neutrophil count decreased	3/369 (0.8%)		3/203 (1.5%)
White blood cell count decreased	1/369 (0.3%)		0/203 (0%)
Hepatic enzyme increased	1/369 (0.3%)		0/203 (0%)
Troponin T increased	1/369 (0.3%)		0/203 (0%)
Weight decreased	1/369 (0.3%)		0/203 (0%)
Alanine aminotransferase increased	1/369 (0.3%)		0/203 (0%)
Blood bilirubin increased	1/369 (0.3%)		0/203 (0%)
Platelet count decreased	1/369 (0.3%)		0/203 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/369 (0.3%)		1/203 (0.5%)
Hyponatraemia	2/369 (0.5%)		0/203 (0%)
Dehydration	1/369 (0.3%)		0/203 (0%)
Diabetes mellitus inadequate control	0/369 (0%)		1/203 (0.5%)
Hypernatraemia	0/369 (0%)		1/203 (0.5%)
Musculoskeletal and connective tissue disorders
Bone pain	1/369 (0.3%)		0/203 (0%)
Myalgia	1/369 (0.3%)		0/203 (0%)
Osteonecrosis	0/369 (0%)		1/203 (0.5%)
Pathological fracture	0/369 (0%)		1/203 (0.5%)
Tendonitis	1/369 (0.3%)		0/203 (0%)
Spinal osteoarthritis	1/369 (0.3%)		0/203 (0%)
Spondylolisthesis	1/369 (0.3%)		0/203 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer	1/369 (0.3%)		0/203 (0%)
Renal cell carcinoma	1/369 (0.3%)		0/203 (0%)
Transitional cell carcinoma	0/369 (0%)		1/203 (0.5%)
Non-small cell lung cancer	2/369 (0.5%)		0/203 (0%)
Invasive ductal breast carcinoma	1/369 (0.3%)		0/203 (0%)
Lung adenocarcinoma	1/369 (0.3%)		0/203 (0%)
Metastatic renal cell carcinoma	1/369 (0.3%)		0/203 (0%)
Myelodysplastic syndrome	0/369 (0%)		1/203 (0.5%)
Prostate cancer	1/369 (0.3%)		0/203 (0%)
Prostate cancer metastatic	1/369 (0.3%)		0/203 (0%)
Nervous system disorders
Syncope	2/369 (0.5%)		1/203 (0.5%)
Cerebrovascular accident	2/369 (0.5%)		1/203 (0.5%)
Presyncope	2/369 (0.5%)		0/203 (0%)
Cerebral infarction	0/369 (0%)		1/203 (0.5%)
Dysarthria	0/369 (0%)		1/203 (0.5%)
Ischaemic stroke	1/369 (0.3%)		0/203 (0%)
Seizure	0/369 (0%)		1/203 (0.5%)
Transient ischaemic attack	0/369 (0%)		1/203 (0.5%)
Psychiatric disorders
Adjustment disorder	1/369 (0.3%)		0/203 (0%)
Anxiety	1/369 (0.3%)		0/203 (0%)
Confusional state	0/369 (0%)		1/203 (0.5%)
Depression	1/369 (0.3%)		0/203 (0%)
Renal and urinary disorders
Proteinuria	1/369 (0.3%)		0/203 (0%)
Haematuria	1/369 (0.3%)		0/203 (0%)
Urinary retention	0/369 (0%)		1/203 (0.5%)
Reproductive system and breast disorders
Prostatitis	1/369 (0.3%)		0/203 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/369 (0.3%)		3/203 (1.5%)
Interstitial lung disease	1/369 (0.3%)		2/203 (1%)
Dyspnoea	0/369 (0%)		3/203 (1.5%)
Pneumothorax	2/369 (0.5%)		0/203 (0%)
Respiratory failure	2/369 (0.5%)		1/203 (0.5%)
Epistaxis	0/369 (0%)		1/203 (0.5%)
Organising pneumonia	1/369 (0.3%)		0/203 (0%)
Pleural effusion	1/369 (0.3%)		0/203 (0%)
Pleurisy	0/369 (0%)		1/203 (0.5%)
Pulmonary fibrosis	1/369 (0.3%)		0/203 (0%)
Pulmonary oedema	2/369 (0.5%)		0/203 (0%)
Skin and subcutaneous tissue disorders
Eczema	1/369 (0.3%)		0/203 (0%)
Surgical and medical procedures
Knee arthroplasty	1/369 (0.3%)		0/203 (0%)
Vascular disorders
Deep vein thrombosis	1/369 (0.3%)		0/203 (0%)
Embolism venous	1/369 (0.3%)		0/203 (0%)
Flushing	0/369 (0%)		1/203 (0.5%)
Hypotension	0/369 (0%)		1/203 (0.5%)
Orthostatic hypotension	0/369 (0%)		1/203 (0.5%)
Subclavian vein thrombosis	0/369 (0%)		1/203 (0.5%)
Thrombosis	0/369 (0%)		1/203 (0.5%)
Arterial disorder	1/369 (0.3%)		0/203 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab SC		Rituximab IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	319/369 (86.4%)		172/203 (84.7%)
Blood and lymphatic system disorders
Neutropenia	104/369 (28.2%)		54/203 (26.6%)
Anaemia	88/369 (23.8%)		40/203 (19.7%)
Gastrointestinal disorders
Nausea	79/369 (21.4%)		47/203 (23.2%)
Constipation	56/369 (15.2%)		34/203 (16.7%)
Diarrhoea	52/369 (14.1%)		20/203 (9.9%)
Vomiting	40/369 (10.8%)		17/203 (8.4%)
Stomatitis	23/369 (6.2%)		11/203 (5.4%)
Abdominal pain	24/369 (6.5%)		12/203 (5.9%)
Dyspepsia	19/369 (5.1%)		14/203 (6.9%)
General disorders
Fatigue	71/369 (19.2%)		29/203 (14.3%)
Pyrexia	40/369 (10.8%)		23/203 (11.3%)
Asthenia	42/369 (11.4%)		24/203 (11.8%)
Mucosal inflammation	29/369 (7.9%)		16/203 (7.9%)
Oedema peripheral	27/369 (7.3%)		9/203 (4.4%)
Investigations
Neutrophil count decreased	81/369 (22%)		43/203 (21.2%)
Weight decreased	28/369 (7.6%)		8/203 (3.9%)
White blood cell count decreased	51/369 (13.8%)		23/203 (11.3%)
Lymphocyte count decreased	53/369 (14.4%)		20/203 (9.9%)
Platelet count decreased	19/369 (5.1%)		11/203 (5.4%)
Metabolism and nutrition disorders
Decreased appetite	28/369 (7.6%)		18/203 (8.9%)
Hypokalaemia	19/369 (5.1%)		5/203 (2.5%)
Musculoskeletal and connective tissue disorders
Back pain	18/369 (4.9%)		11/203 (5.4%)
Nervous system disorders
Neuropathy peripheral	44/369 (11.9%)		24/203 (11.8%)
Paraesthesia	32/369 (8.7%)		13/203 (6.4%)
Headache	21/369 (5.7%)		15/203 (7.4%)
Psychiatric disorders
Insomnia	23/369 (6.2%)		13/203 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	42/369 (11.4%)		19/203 (9.4%)
Dyspnoea	22/369 (6%)		6/203 (3%)
Skin and subcutaneous tissue disorders
Alopecia	87/369 (23.6%)		48/203 (23.6%)

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.