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

Lymphoma, Large B-Cell, Diffuse Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01649856
• Other study ID #: MO28107
• Secondary ID: 2012-000669-19
• Status: Completed
• Phase: Phase 3
• First received: July 23, 2012
• Last updated: September 11, 2017
• Start date: August 24, 2012
• Est. completion date: September 16, 2016

Study information

• Verified date: September 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 572
• Est. completion date: September 16, 2016
• Est. primary completion date: October 21, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• CHOP
CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles
• 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
• rituximab [MabThera/Rituxan]
375 mg/m2 intravenously on Day 1 of each cycle, 8 cycles

Locations

Country	Name	City	State
Algeria	EHS CAC Hospital FRANTZ FANON ZABANA BLIDA; Hematology ward	Blida
Algeria	Centre hospitalo-univerisitaire de Tizi Ouzou - Nedir Mohamed;Service d'hématologie	Tizi Ouzou
Argentina	Cemic; Haematology	Buenos Aires
Argentina	Hospital Privado de Comunidad; Oncology	Mar Del Plata
Belgium	Onze Lieve Vrouwziekenhuis Aalst	Aalst
Belgium	ZNA Middelheim	Antwerpen
Belgium	CHU Brugmann (Victor Horta)	Bruxelles
Belgium	Clin Univ de Bxl Hôpital Erasme	Bruxelles
Belgium	CHU Charleroi-ISPPC-Espace Santé	Charleroi
Belgium	CHU de Charleroi	Charleroi
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Gent	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	AZ Turnhout Sint Elisabeth	Turnhout
Belgium	CHR de Verviers - East Belgium	Verviers
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Hospital Amaral Carvalho	Jau	SP
Brazil	Hospital Giovanni Battista - Mae de Deus Center; Instituto do Cancer	Porto Alegre	RS
Brazil	Clinicas Oncologicas Integradas - COI	Rio De Janeiro	RJ
Brazil	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ
Brazil	Hospital das Clinicas - FMUSP; Hematologia	Sao Paulo	SP
Bulgaria	University Hospital Sv.Georgi Clnic of Hematology; Hematology	Plovdiv
Bulgaria	Military Medical Academy; Hematology And Oncology	Sofia
Bulgaria	UMHAT Alexandrovska EAD; Hematology	Sofia
Canada	Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials	Barrie	Ontario
Canada	William Osler Health System Brampton Civic Hospital	Brampton	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	Regional health authority A vitalite health network	Moncton	New Brunswick
Canada	Southlake Regional Health Center; Community Care Clinic / Oncology	Newmarket	Ontario
Canada	Lion'S Gate Hospital	North Vancouver	British Columbia
Canada	Toronto East General Hospital; Haematology/Oncology	Toronto	Ontario
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Colombia	Clínica Imbanaco; Oncology	Cali
Colombia	Hospital Pablo Tobon Uribe	Medellin-Antioquia
Finland	Helsinki University Central Hospital; Dept of Oncology	Helsinki
Finland	Middle Finland Central Hospital	Jyväskylä
Finland	Oulu University Hospital; Oncology	Oulu
Finland	Tampere University Hospital; Dept of Oncology	Tampere
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
France	Ch Victor Dupouy; Hematologie	Argenteuil
France	Hopital Augustin Morvan; Hematologie	Brest
France	Ch Du Mans; Medecine Hematologie Oncologie	Le Mans
France	Centre ONCOGARD - Institut de Cancerologie du Gard	Nimes
France	Ch De Saint Quentin; Medecine B10	Saint Quentin
France	Hopital Sud; Hematologie Clinique	Salouel
France	Hopital Yves Le Foll; Hematologie Oncologie	St Brieuc
France	Clinique Ste Anne	Strasbourg
France	Hopital Hautepierre; Hematologie Oncologie	Strasbourg
France	Hia Sainte Anne; Medecine Interne Oncologie	Toulon
Greece	University General Hospital of Alexandroupolis; Haemotology	Alexandroupolis
Greece	General Hospital of Athens Evangelismos; Hematology	Athens
Greece	Laiko General Hospital; Hematology Clinic	Athens
Greece	Metropolitan Hospital; Hematology Dept	Athens
Greece	Periph. University General Hospital of Heraklion; Hematology	Heraklion
Greece	University Hospital of Ioannina; Hematology	Ioannina
Greece	University Hospital Of Patras; Dept. Of Internal Medicine-Hematology Division	Patras
Greece	Georgios Papanikolaou Hospital; Hematology Department	Thessaloniki
Greece	Theagenio Anticancer Hospital; Dept. of Haematology	Thessaloniki
Ireland	Cork Uni Hospital; Oncology Dept	Cork
Ireland	Mater Misericordiae Uni Hospital; Oncology	Dublin
Ireland	St James' Hospital; Cancer Clinical Trials Office	Dublin
Ireland	Galway Uni Hospital; Oncology Dept	Galway
Ireland	University Hospital Limerick - Oncology	Limerick
Israel	Haemek Medical Center; Hematology Department	Afula
Israel	Rambam Medical Center; Heamatology & Bone Marrow Transplantation	Haifa
Israel	Wolfson Mc; Haematology	Holon
Israel	Shaare Zedek Medical Center; Hematology Dept.	Jerusalem
Israel	Meir Medical Center; Heamatology Dept	Kfar Saba
Israel	Beilinson Medical Center; Haematology	Petach Tikva
Israel	Chaim Sheba Medical Center; Hematology BMT & CBB	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Ichilov Sourasky Medical Center; Heamatology	Tel Aviv
Italy	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia
Italy	ASST PAPA GIOVANNI XXIII; Ematologia	Bergamo	Lombardia
Italy	Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.	Cagliari	Sardegna
Italy	ASST DI CREMONA; U.O.S. di Ematologia	Cremona	Lombardia
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Azienda Ospedaliero Uni Ria Policlinico G. Martino; U.O. Di Oncologia Medica	Messina	Sicilia
Italy	Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia	Padova	Veneto
Italy	Casa Di Cura La Maddalena; Oncoematologia E Trapianto Del Midollo Osseo	Palermo	Sicilia
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria
Italy	Ospedale Civile; S.C. Ematologia	Pesaro	Marche
Italy	Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia	Pescara	Abruzzo
Italy	Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia	Ravenna	Emilia-Romagna
Italy	Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia	Rimini	Emilia-Romagna
Italy	Az. Osp. Sant'Andrea; U.O. C. Ematologia	Roma	Lazio
Italy	Uni Cattolica; Divisione Di Ematologia	Roma	Lazio
Italy	Az. Osp. G. Moscati; U.O. Do Ematologia	Taranto	Puglia
Italy	Ospedale Mauriziano Umberto I	Torino	Piemonte
Italy	A.O. Univ.Ospedali Riuniti Umerto I -G.M.Lancisi G.Salesi; U.O. Clinica Di Ematologia	Torrette Di Ancona	Marche
Italy	AOU Ospedali Riuniti; Ematologia	Trieste	Friuli-Venezia Giulia
Italy	Ospedale Di Circolo E Fondazione Macchi; Ematologia	Varese	Lombardia
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Meander Medisch Centrum; Locatie Lichtenberg	Amersfoort
Netherlands	Deventer Ziekenhuis; Interne Geneeskunde	Deventer
Netherlands	Albert Schweitzer Ziekenhuis	Dordrecht
Netherlands	Maxima Medisch Centrum; Inwendige Geneeskunde	Eindhoven
Netherlands	Groene Hart Ziekenhuis Bleulandlocatie; Inwendige Geneeskunde	Gouda
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Atrium Medisch Centrum	Heerlen
Netherlands	Spaarne Ziekenhuis; Inwendige Geneeskunde	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden; Interne	Leeuwarden
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Netherlands	Erasmus Mc - Locatie Centrum; Dept of Hematology	Rotterdam
Netherlands	Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed	Rotterdam
Netherlands	Maasstad ziekenhuis	Rotterdam
Netherlands	Zuyderland ziekenhuis locatie Geleen	Sittard-Geleen
Netherlands	Isala Klinieken, Locatie Sophia; Inwendige Geneeskunde	Zwolle
Peru	Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica	Chiclayo
Peru	Instituto;Oncologico Miraflores	Lima
Peru	Oncosalud Sac; Oncología	Lima
Poland	Katedra i Klinika Hematologii i Transplantacji Szpiku SUM	Katowice
Poland	Swietokrzyskie Centrum Onkologii; Onkologia Ogolna	Kielce
Poland	Malopolskie Centrum Medyczne	Krakow
Poland	Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej	Opole
Poland	Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddzial Chorób Wewnetrznych/Hematologiczny	Slupsk
Poland	Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego	Warszawa
Portugal	HUC; Servico de Hematologia	Coimbra
Portugal	Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula	Lisboa
Portugal	Hospital Santo Antonio dos Capuchos; Servico de Hemato-Oncologia	Lisboa
Portugal	Hospital de Sao Joao; Servico de Hematologia Clinica	Porto
Portugal	IPO do Porto; Servico de Onco-Hematologia	Porto
Russian Federation	Regional Oncology Center	Chelyabinsk
Russian Federation	Central City Hospital #7; Hematology	Ekaterinburg
Russian Federation	Republican Clinical Oncologic Dispensary of Republic Of Tatarstan	Kazan
Russian Federation	N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis	Moscow
Russian Federation	Rus Med Academy for Postgraduate Education; Oncology Department	Moscow
Russian Federation	Vladimirskiy Regional Scientific Research Inst. ; Hematology	Moscow
Russian Federation	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod
Russian Federation	Clinical MSCh No1	Perm
Russian Federation	City Clinical Hospital #15; Hematology department	Saint-Petersburg
Russian Federation	Saint-Petersburg SHI City Clinical Hospital #31	St. Petersburg
Saudi Arabia	Riyadh Military Hospital	Riyadh
Serbia	Clinical Center Kragujevac;Center for Hematology	Kragujevac
Serbia	Clinic of Haematology Cc Nis	NIS
South Africa	National Hospital; Oncotherapy Dept	Bloemfontein
South Africa	Tygerberg Hospital; Haematology Department	Cape Town
South Africa	Steve Biko Academic Hospital; Oncology	Pretoria
Spain	Hospital Punta Europa; Servicio de Hematologia	Algeciras	Cadiz
Spain	Hospital General Univ. de Alicante; Servicio de Oncologia	Alicante
Spain	Hospital de Cruces; Servicio de Hematologia	Barakaldo	Vizcaya
Spain	Hospital de Cabueñes; Servicio de Hematología y Hemoterapia	Gijon	Asturias
Spain	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Hematologia	Girona
Spain	Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia	Las Palmas de Gran Canaria	Las Palmas
Spain	Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Hematologia	Las Palmas de Gran Canarias	Las Palmas
Spain	Hospital Lucus Augusti; Servicio de Hematologia	Lugo
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Hematología	Madrid
Spain	Hospital Univ. 12 de Octubre; Servicio de Hematologia	Madrid
Spain	Hospital Universitario la Paz; Servicio de Hematologia	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Madrid
Spain	Hospital Costa del Sol; Servicio de Hematologia	Malaga
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Hematologia	Sabadell	Barcelona
Spain	Hospital de Donostia; Servicio de Hematologia	San Sebastian	Guipuzcoa
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Hematologia	Santander	Cantabria
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Hospital Universitario Dr. Peset; Servicio de Hematologia	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa; Servicio de Hematologia	Zaragoza
Spain	Hospital Universitario Miguel Servet; Servicio Hematologia	Zaragoza
Thailand	King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine	Bangkok
Thailand	Ramathibodi Hospital; Division of Hematology, Department of Medicine	Bangkok
Thailand	Siriraj Hospital; Division of Hematology, Department of Medicine	Bangkok
Thailand	Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine	Khon Kaen
Turkey	Cukurova Uni ; Hematology	Adana
Turkey	Ankara University; Hematology	Ankara
Turkey	Diskapi Research And Training Hospital; hematology	Ankara
Turkey	Hacettepe Uni Medical Faculty; Hematology	Ankara
Turkey	Gaziantep Uni Medical School; Hematology	Gaziantep
Turkey	Istanbul University Cerrahpasa Medical Faculty; Hematology Department	Istanbul
Turkey	Dokuz Eylul Uni ; Hematology	Izmir
Turkey	Ege Uni Medical School; Hematology	Izmir
Turkey	Erciyes Uni ; Hematology	Kayseri
Turkey	Ondokuzmayis University Medical Faculty Heamatology Department	Samsun
Turkey	Cumhuriyet Uni. Med. Fac.; Hematology	Sivas
Turkey	Karadeniz Technical Uni School of Medicine; Hematology	Trabzon
Ukraine	Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU; Chair of Oncology and Medical Radiology	Dnipropetrovsk
Ukraine	Kyiv City Clinical Oncological Center; Chemotherapy Department	Kiev
Ukraine	State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department	Lviv
United Kingdom	SOUTHMEAD HOSPITAL; Richard Bright Dialysis Centre	Bristol
United Kingdom	Ipswich Hospital; Oncology Pharmacy	Ipswich
United Kingdom	Macclesfield District General Hospital	Macclesfield
United Kingdom	Kings Mill Hospital	Sutton in Ashfield
United Kingdom	Singleton Hospital: Pharmacy Department	Swansea
Venezuela	Banco Municipal de Sangre; Hematología	Caracas
Venezuela	Instituto de Oncologia y Hematologia UCV	Caracas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Algeria,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  Colombia,  Finland,  France,  Greece,  Ireland,  Israel,  Italy,  Netherlands,  Peru,  Poland,  Portugal,  Russian Federation,  Saudi Arabia,  Serbia,  South Africa,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom,  Venezuela, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Complete Response (CR) or Complete Response Unconfirmed (CRu)	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).	Up to approximately 4.25 years
Secondary	Cancer Treatment Satisfaction Questionnaire (CTSQ) Domain Scores	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.	At Cycle 7 (each cycle was 14 or 21 days)
Secondary	Rituximab Administration Satisfaction Questionnaire (RASQ) Domain Scores	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.	At Cycle 7 (each cycle was 14 or 21 days)
Secondary	Median Duration of Rituximab Administration for Each Treatment Cycle	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.	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)
Secondary	Percentage of Participants by Time Spent in the Infusion Chair/Bed for Each Treatment Cycle	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".	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)
Secondary	Percentage of Participants by Time Spent in the Hospital for Each Treatment Cycle	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".	Cycles 1, 2, 3, 4, 5, 6, 7, and 8 (each cycle was 14 or 21 days)
Secondary	Number of Participants With an Event-Free Survival (EFS) Event	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.	Up to approximately 4.25 years
Secondary	Duration of EFS	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.	Up to approximately 4.25 years
Secondary	Number of Participants With Relapse or Death at the Time of Primary Analysis	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.	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)
Secondary	Duration of Disease-Free Survival (DFS)	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.	Up to approximately 4.25 years
Secondary	Number of Participants With Progression, Relapse, or Death	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.	Up to approximately 4.25 years
Secondary	Duration of Progression-Free Survival (PFS)	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.	Up to approximately 4.25 years
Secondary	Number of Deaths		Up to approximately 4.25 years
Secondary	Duration of Overall Survival (OS)	OS was defined as the time from randomization to death from any cause.	Up to approximately 4.25 years