A Study of Rituximab (MabThera) Subcutaneous (SC) Versus Rituximab (MabThera) Intravenous in Participannts With Follicular Non-Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

A Two-Stage Phase III, International, Multi-Center, Randomized, Controlled, Open-Label Study to Investigate the Pharmacokinetics, Efficacy and Safety of Rituximab SC in Combination With CHOP or CVP Versus Rituximab IV in Combination With CHOP or CVP in Patients With Previously Untreated Follicular Lymphoma Followed by Maintenance Treatment With Either Rituximab SC or Rituximab IV

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01200758
• Other study ID #: BO22334
• Secondary ID: 2010-021377-36
• Status: Completed
• Phase: Phase 3
• Start date: February 15, 2011
• Est. completion date: October 31, 2017

Study information

• Verified date: October 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This two-stage, multi-center, randomized, controlled, open-label study will investigate the pharmacokinetics, efficacy and safety of rituximab SC versus rituximab IV in participants with previously untreated follicular non-Hodgkin's lymphoma. Participants will be randomized to receive 375 milligrams per meter square (mg/m^2) rituximab as IV infusion or 1400 milligrams (mg) rituximab SC. In addition, participants will receive standard chemotherapy. Participants who achieved a complete or partial response (PR) after 8 treatment cycles, will receive maintenance treatment for a further maximum number of 12 cycles. Maintenance treatment cycles will be repeated every 8 weeks. This is a two-stage study. Stage 1 was designed to confirm the chosen rituximab SC dose resulting in comparable rituximab serum Ctrough levels compared with rituximab IV, when given as part of induction treatment every 3 weeks. Enrollment for Stage 2 started after the rituximab SC dose was established in Stage 1. Stage 2 aimed to further investigate the efficacy and safety of rituximab SC compared with rituximab IV. The anticipated time on study treatment is 96 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 410
• Est. completion date: October 31, 2017
• Est. primary completion date: June 12, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cluster of differentiation 20 (CD20)-positive, follicular Non-Hodgkin's lymphoma grade 1, 2, 3a. A tumor biopsy must have been performed within 6 months before study entry with material available for central review

• No prior treatment

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

• Grade 3b follicular lymphoma

• Transformation to high-grade lymphoma secondary to follicular lymphoma

• Types of Non-Hodgkin's lymphoma other than follicular lymphoma

• Presence or history of central nervous system (CNS) disease

• Corticoid therapy during the last 4 weeks, except prednisone treatment less than (<) 20 milligrams per day (mg per day)

• Known active bacterial, viral, fungal, or mycobacterial, or any major episode of infections requiring hospitalization or treatment with IV antibiotics within 4 weeks of start of study medication, or oral antibiotics within 2 weeks prior to start of study medication

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Rituximab SC
First cycle of rituximab IV infusion (375 mg/m^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.
• Rituximab IV
Eight cycles of rituximab IV infusion (375 mg/m^2; rituximab induction) administered every 3 weeks. Participants achieving at least PR during induction, entered rituximab IV maintenance therapy (375 mg/m^2) once every 8 weeks for 24 months.
• Cyclophosphamide
Eight cycles of cyclophosphamide (750 mg/m^2 IV) administered every 3 weeks.
• Doxorubicin
Eight cycles of doxorubicin (50 mg/m^2 IV) administered every 3 weeks.
• Vincristine
Eight cycles of doxorubicin (1.4 mg/m^2 IV) administered every 3 weeks.
• Prednisone/Prednisolone
Eight cycles of prednisone/prednisolone (100 mg/day or 40 mg/m^2/day IV/orally) administered Days 1 to 5 of every 21 days cycle.

Locations

Country	Name	City	State
Australia	Gosford Hospital; Cancer Care Services	Gosford	New South Wales
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Gold Coast Hospital; Haematology Department	Southport	Queensland
Australia	Wollongong Hospital; Cancer Services	Wollongong	New South Wales
Australia	Queen Elizabeth Hospital; Haematology	Woodville South	South Australia
Belgium	UZ Antwerpen	Edegem
Belgium	CHU Sart-Tilman	Liège
Belgium	Sint Augustinus Wilrijk	Wilrijk
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska, Clinic for Internal Disease, Hematology Dept	Banja Luka
Bosnia and Herzegovina	University Clinical Center Sarajevo, Clinic for Hematology	Sarajevo
Bosnia and Herzegovina	University Clinical Centre Tuzla, Clinic for Oncology, Hematology and Radiotherapy	Tuzla
Brazil	Nucleo de Hematologia e Transplante de Medula Ossea de Minas Gerais	Belo Horizonte	MG
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Brazil	Santa Casa de Misericordia de Sao Paulo; Hematologia e Hemoterapia	Sao Paulo	SP
Bulgaria	UMHAT Dr Georgi Stranski; Hematology	Pleven
Bulgaria	Umhat S. George; Hematology	Plovdiv
Bulgaria	Specialised Hospital For Treatment Of Hematological Diseases; Hematology	Sofia
Bulgaria	Mhat Sveta Marina; Dept. of Haematology	Varna
Canada	Queen Elizabeth II Health Sciences Centre; Oncology	Halifax	Nova Scotia
Canada	Cite de La Sante de Laval; Hemato-Oncologie	Laval	Quebec
Canada	CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie	Quebec
Canada	Centre de sante et de services sociaux Rimouski Neigette	Rimouski	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec
Colombia	Fundacion Cardioinfantil	Bogota
Colombia	Centro Medico Imbanaco	Cali
Colombia	Hospital Pablo Tobon Uribe	Medellin-Antioquia
Colombia	Oncólogos de Occidente	Pereira
Croatia	UHC Rijeka	Rijeka
Croatia	University Hospital Center Zagreb; Haematology Department	Zagreb
Denmark	Aarhus Universitetshospital, Hæmatologisk Afdeling R	Århus
Denmark	Herlev Uni Hospital; Hæmatologisk Afdeling L 121	Herlev
Denmark	Rigshospitalet; Hæmatologisk Klinik	København Ø
Denmark	Odense Universitetshospital; Hæmatologisk Afdeling	Odense C
Denmark	Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium	Roskilde
Denmark	Vejle Hospital; Dept of Medicine, Division of Hematology	Vejle
Finland	Helsinki University Central Hospital; Dept of Oncology	Helsinki
France	Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie	Bordeaux
France	Hopital Henri Mondor; Hematologie Clinique	Creteil
France	Chu Site Du Bocage;Hematologie Clinique	Dijon
France	Clinique Victor Hugo; Chimiotherapie	Le Mans
France	Institut J Paolii Calmettes; Onco Hematologie 1	Marseille
France	Hopital Saint Eloi; Hematologie Oncologie Medicale	Montpellier
France	Hopital Hotel Dieu Et Hme;Hopital De Jour	Nantes
France	Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)	Paris
France	Hopital De Haut Leveque; Hematologie Clinique	Pessac
France	Ch Lyon Sud; Hemato Secteur Jules Courmont	Pierre Benite
France	Hopital De La Miletrie; Hematologie Et Oncologie Medicale	Poitiers
France	Hopital Bretonneau; Hematologie Therapie Cellulaire	Tours
Georgia	Chemotherapy and Immunotherapy Clinic Medulla	Tbilisi
Georgia	Institute of Hematology and Transfusiology	Tbilisi
Georgia	M.Zodelava's Hematology Center	Tbilisi
Georgia	Mediclub	Tbilisi
Germany	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin
Germany	Klinikum Darmstadt GmbH; Med. Klinik V; Onkologie & Hämatologie	Darmstadt
Germany	Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex; Fachaerzte fuer Innere Medizin	Dresden
Germany	PIOH PD Dr. R. Schnell - Dr. H. Schulz - Dr. M. Hellmann	Frechen
Germany	Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik I	Giessen
Germany	Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik	Greifswald
Germany	Internistisch-Onkologische Gemeinschaftspraxis; Dres. Rohrberg, Hurtz, Schma usw.	Halle
Germany	Medizinische Hochschule; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie	Hannover
Germany	St. Vincentius Kliniken Ag; Medizinische Klinik Abt. 2	Karlsruhe
Germany	UKSH Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie	Kiel
Germany	Gemeinschaftspraxis PD Dr. med. Marcel Reiser und Dr. med. Ildiko Kátay	Koeln
Germany	Onkologische Gemeinschaftspraxis	Magdeburg
Germany	Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach	Marburg
Germany	Medizinisches Versorgungszentrum MOP	München
Germany	Praxis Dr.med. Jens Uhlig	Naunhof
Germany	Praxis Dr. Clemens Müller-Naendrup (Onkologische Schwerpunktpraxis im MVZ 2 GmbH)	Olpe
Germany	Prosper-Hospital, Medizinische Klinik I	Recklinghausen
Germany	Praxis Dr. Fenchel	Saalfeld
Germany	Caritas Kilinik St. Theresia; Abt. Innere Medizin	Saarbruecken
Germany	Praxis für Hämatologie & Onkologie	Saarbruecken
Greece	Attiko Hospital; Haematology Clinic	Athens
Greece	Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine	Athens
Italy	A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia	Brescia	Lombardia
Italy	Uni Degli Studi Di Genova; 1A Divisione Di Ematologia	Genova	Liguria
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia	Milano	Lombardia
Italy	A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica	Napoli	Campania
Italy	Azienda Ospedaliera Ospedale S.Carlo; Ematologia	Potenza	Basilicata
Italy	AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia	Reggio Emilia	Emilia-Romagna
Italy	Ospedale S. Eugenio; Divisione Di Ematologia	Roma	Lazio
Italy	IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo	San Giovanni Rotondo	Puglia
Italy	Ospedale Ca Foncello; Ematologia	Treviso	Veneto
Italy	Ospedale Di Vicenza; Nefrologia, Ematologia	Vicenza	Veneto
Macedonia, The Former Yugoslav Republic of	University Clinic for Hematology; HSCT Department	Skopje
Macedonia, The Former Yugoslav Republic of	University Clinic of Hematology Skopje, Hospital Care Department	Skopje
Malaysia	Ampang Hospital; Department of Haematology	Ampang
Malaysia	University Malaya Medical Center; Hematology Unit of Department of Internal Medicine	Kuala Lumpur	FED. Territory OF Kuala Lumpur
Malaysia	Sarawak General Hospital; Department of Radiotherapy, Oncology and Palliative care	Sarawak
Mexico	Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre	Chihuahua
Mexico	Hospital General De Culiacan; Servicio De Hematologia	Culiacan
Mexico	Hospital Universitario Dr. Jose E. Gonzalez; Haematology	Monterrey
Mexico	Centro de Estudios Clinicos de Queretaro (CECLIQ)	Queretaro
New Zealand	Canterbury Health Laboratories; Haematology	Christchurch
New Zealand	Palmerston North Hospital; Regional Cancer Treatment Service	Palmerston North
Peru	Hospital Maria Auxiliadora	Lima
Peru	Instituto;Oncologico Miraflores	Lima
Peru	Oncosalud Sac; Oncología	Lima
Romania	Spitalul Clinic Judetean de Urgenta Brasov,Clinica de Hematologie	Brasov
Romania	Fundeni Clinical Inst. ; Hematology Dept	Bucharest
Romania	Institutul Regional de Oncologie Iasi; Clinica de Hematologie	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi, Clinica de Hematologie	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie	Targu-mures
Romania	Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie	Timisoara
Russian Federation	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan
Russian Federation	Haematology Research Center; Haematology	Moscow
Russian Federation	N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis	Moscow
Russian Federation	Penza Regional Oncology Dispensary	Penza
Russian Federation	St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta	Saint-Petersburg
Russian Federation	Research Inst. of Hematology & Blood Transfusion ; Hematology	St Petersburg
Russian Federation	Russian Scientific Center of Radiology and Surgical Technologies; Dept of Radiology	St.Petersburg, Pesochny
Serbia	Institute of Hematology	Belgrade
Serbia	Clinical Center Vojvodine; Clinic for Hematology	Novi Sad
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Singapore	Singapore General Hospital; Department of Haematology	Singapore
Slovakia	National Cancer Inst. ; Dept. of Chemotherapy	Bratislava
Slovakia	St. Elisabeths Cancer Center	Bratislava
South Africa	National Hospital; Oncotherapy Dept	Bloemfontein
South Africa	King Edward VIII; Department of Haematology	Congella
South Africa	Durban Oncology Center	Durban
South Africa	University of Witwatersrand/Johannesburg Hospital; Dept. of ocnology	Johannesburg
South Africa	Cancercare	Kraaifontein
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital del Mar; Servicio de Hematologia	Barcelona
Spain	Hospital Duran i Reynals; Servicio de Hematologia	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona
Spain	Hospital Universitario Puerta del Mar; Servicio de Hematologia	Cádiz	Cadiz
Spain	Hospital Ramon y Cajal; Servicio de Hematologia	Madrid
Spain	Hospital Universitario de la Princesa; Servicio de Hematologia	Madrid
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia	Murcia
Spain	Hospital Clinico Universitario de Salamanca;Servicio de Hematologia	Salamanca
Spain	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Thailand	National Cancer Inst.	Bangkok
Thailand	Siriraj Hospital; Division of Hematology, Department of Medicine	Bangkok
Thailand	Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine	Khon Kaen
Turkey	Adana Baskent University Hospital; Medical Oncology	Adana
Turkey	Bilim University School of Medicine; Hematology	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty; Hematology Department	Istanbul
Turkey	Dokuz Eylul Uni ; Hematology	Izmir
Turkey	Ege Uni Medical School; Hematology	Izmir
United Kingdom	Ninewells Hospital & Medical School; Ward 34	Dundee
United Kingdom	Maidstone & Tonbridge Wells Hospital; Kent Oncology Center	Maidstone
United Kingdom	Derriford Hospital; Department of Haematology	Plymouth
United Kingdom	Queen's Hospital; Oncology	Romford
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Pinderfields General Hospital; Dept of Haematology	Wakefield
United Kingdom	New Cross Hospital; Dept. Of Haematology	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Colombia,  Croatia,  Denmark,  Finland,  France,  Georgia,  Germany,  Greece,  Italy,  Macedonia, The Former Yugoslav Republic of,  Malaysia,  Mexico,  New Zealand,  Peru,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovakia,  South Africa,  Spain,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage I: Trough Serum Concentrations (Ctrough) of IV and SC Rituximab		Stage I: Cycle (Cy) 7 Day (D) 21 (within 2 hours predose on Cy8) of induction treatment (1 Cy=3 weeks)
Primary	Stage II: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for Non-Hodgkin Lymphoma (NHL)	Overall Response comprised complete response (CR), CR unconfirmed (CRu), or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and computed tomography (CT) scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by more than (>) 75% in the sum of the products of greatest diameters (SPD); PR: Greater than or equal to (=) 50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.	Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Secondary	Stage I: Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL	Overall Response comprised CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in the SPD; PR: =50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI was estimated for one sample binomial using Pearson-Clopper.	Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Secondary	Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL	Overall Response comprised of CR, CRu, or PR. A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumour response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD; PR: =50% decrease in SPD of 6 largest dominant nodes or nodal masses. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.	Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Secondary	Stage I: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL	Complete Response was comprised CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.	Stage I: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Secondary	Stage II: Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL	Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.	Stage II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Secondary	Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Induction Treatment Assessed Using International Working Group Response Criteria for NHL	Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.	Stage I and II: Baseline up to end of induction treatment Cy8 (24 weeks) (1 Cy=3 weeks)
Secondary	Stage I and II (Pooled): Percentage of Participants With Complete Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL	Complete Response comprised of CR and CRu. A participant was defined as a responder if they sustained a CR or CRu at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.	Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)
Secondary	Stage I and II (Pooled): Percentage of Participants With Overall Response at the End of Maintenance Treatment Assessed Using International Working Group Response Criteria for NHL	Overall Response comprised of CR, CRu, or PR . A participant was defined as a responder if they sustained a CR, CRu or PR at the end of induction treatment. Response assessment was based on clinical examination and CT scans. Assessment of tumor response was performed according to the International Working Group response criteria for NHL. CR: complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy; CRu: CR along with regression in lymph node mass by >75% in SPD. The 95% CI for the response rates was estimated for one sample binomial using Pearson-Clopper.	Stage I and II: Baseline up to 57 days after last maintenance dose (last maintenance dose: maintenance Cy12/Study Cy20 [30 months]) (up to data cutoff of 31 Oct 2017 [up to 6 years]) (1 Cy=8 weeks)
Secondary	Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse or Death	Disease progression: =50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or =50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Progression-Free Survival (PFS) Assessed Using International Working Group Response Criteria for NHL	PFS was defined as the time from randomization to disease progression/relapse or death due to any cause. If the specified event (disease progression/relapse, death) did not occur, PFS was censored at the last tumor assessment date showing no disease progression, either during treatment or follow-up. Disease progression: =50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or =50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. PFS analysis was performed using Kaplan - Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Percentage of Participants With Disease Progression/Relapse, New Anti-Lymphoma Treatment or Death Assessed Using International Working Group Response Criteria for NHL	Disease progression: =50% increase from nadir in the SPD of any previously identified abnormal node or appearance of any new lesion during or at the end of therapy or =50% increase in the greatest diameter of any previously identified node >1 cm in its short axis or in the SPD of more than one node. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Event-Free Survival Assessed Using International Working Group Response Criteria for NHL	Event-free survival was defined as the time from randomization to disease progression/relapse, death or initiation of new NHL therapy. If the specified event (progression/relapse, death or new anti-lymphoma treatment) did not occur, event-free survival was censored at the last tumor assessment date either during treatment or follow up. Event-free survival analysis was performed using Kaplan-Meier curves. Baseline, D1 of all cycles (Cy 1-20) (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), at early withdrawal, at follow-up, every 12 weeks for 96 weeks or until documented disease progression/relapse or death (up to a median of 27 months; up to data cutoff of 31 Oct 2017 [up to 6 years])	Baseline up to disease progression or death up to data cutoff of 31 Oct 2017 (up to 6 years) (See detailed timeframe in Outcome Measure description)
Secondary	Percentage of Participants Who Died		Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])
Secondary	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. Participants without event were censored at the time of last follow-up information for survival, ie, at the last time known to be alive.	Baseline up to death (up to data cutoff of 31 Oct 2017 [up to 6 years])
Secondary	Stage I: Observed Area Under the Serum Concentration-Time Curve (AUC) of Rituximab	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Predose (within 2 hr) and 24 hrs postdose on Cy 7 (D1,3,7,15), predose (0 hr) on Cy 8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy 7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])	Stage I (Induction): Predose (within 2 hour [hr]) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I: Maximum Serum Concentrations (Cmax) of IV and SC Rituximab	Predose (within 2 hr) and 24 hrs postdose on Cy7 (D1,3,7,15), predose (0 hr) on Cy8 D1 (1 Cy=3 weeks); additionally within 15 minutes after end of infusion (infusion duration=30 minutes) on Cy7 D1 for rituximab IV (up to data cutoff of 11 Apr 2012 [up to 26 months])	Stage I (Induction): Predose (within 2hr) up to data cutoff of 11 Apr 2012 [up to 26 months]) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Ctrough of Rituximab at Each Induction Treatment Cycle	Stage I and II (Induction): Rituximab IV: Predose (within 2 hr) on D1 of Cy1-8 (1 Cy=3 weeks & 4 weeks for Cy8); Rituximab SC: Predose (within 2 hr) on D1 of Cy1 & Cy3-8 (1 Cy=3 weeks and 4 weeks for Cy8), predose (within 2 hr) on D0 of Cy2 (up to data cutoff of 31 Oct 2013 [up to 32 months])	Stage I and II (Pooled): Predose (within 2hr) up to data cutoff of 31 Oct 2013 [up to 32 months]) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Ctrough of Rituximab at Each Maintenance Treatment Cycle	Stage I and II (maintenance): D29 of Cy8 (induction; 1 Cy=4 weeks), predose (within 2 hr) on D1 of Cy9 to 19 (maintenance Cy1 to 12 [1 Cy=8 weeks]; up to data cutoff of 11 Jan 2016 [up to 6 years])	Stage I and II (maintenance): Predose (within 2hr) up to data cutoff of 11 Jan 2016 [up to 6 years]) (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Rituximab Levels 12 Weeks, 24 Weeks, and 36 Weeks After the Last Rituximab Administration		12 weeks, 24 weeks, and 36 weeks after the last rituximab administration (up to data cutoff of 11 Jan 2016 [up to 6 years])
Secondary	Percentage of Participants With B-Cell Depletion by Cycle for Induction Phase	Depletion is defined as a cluster of differentiation (CD) 19 value <80 cells per cubic millimeter (cells/mm^3).	Stage I and II (induction): for rituximab IV - D1 of Cy 1 to 8 (1 Cy=3 weeks); for rituximab SC - D1 of Cy 1 and Cy 3 to 8, D0 of Cy 2
Secondary	Percentage of Participants With B-Cell Depletion by Cycle for Maintenance Phase	Depletion is defined as a CD19 value <80 cells/mm^3.	Stage I and II (maintenance): D1 of Cy 9 to 20 (1 Cy=8 weeks) (up to data cutoff of 11 Jan 2016 [up to 6 years])
Secondary	Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Chimeric Antibodies (HACAs) to Rituximab	Levels of HACA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])	Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Percentage of Participants Positive for Human Anti-Human Antibodies (HAHAs) to Rituximab	Levels of HAHA in serum were detected at Day 1 of each cycle up to Cycle 8 and at follow-up visit. Stage I and II: Baseline: pre-dose (72 hours prior) D1 of Cy1, Cy 3-20, D0 of Cy2 (1 Cy=3 weeks for Cy1-8 & 8 weeks for Cy9-20), post-baseline: every 12 weeks after last rituximab administration until 96 weeks (a median of 27 months; up to data cutoff of 11 Jan 2016 [up to 6 years])	Stage I and II: Baseline, post-baseline (See detailed timeframe in Outcome Measure description)
Secondary	Stage I and II (Pooled): Percentage of Responses Showing Time Saved of Staff as Per Physician/Nurse Opinions With Each Administration of Rituximab SC as Compared to Rituximab IV at the End of Cy 8, 15 and 20	All investigator physicians and nurses involved in this study were asked to provide the staff time that could be saved with each administration of rituximab SC as compared with rituximab IV to participants in routine practice afetr Cy 8, 15, 20 and categorized as less than (<) 1 hr, at least 1 hr but <2 hrs, at least 2 hrs but <3 hrs, at least 3 hrs but <4 hrs, >/=4 hrs. Staff were asked not to consider the time needed for the first IV administration. Analysis was done in all participants to show a comparison on the time saved by staffs when administered via SC and IV.	After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)
Secondary	Percentage of Responses Who Showed Rituximab SC Formulation Convenient as Compared to Rituximab IV Formulation as Assessed by Physician/Nurse Opinion	All investigator physicians and nurses involved in this study were asked to complete question i.e. "Which formulation of rituximab (SC or IV) do you think is more convenient?" based on their experience with the rituximab SC and IV formulations across all participants and presented as rituximab SC is much more convenient; rituximab SC is a little more convenient; both formulations are equally convenient; rituximab IV is a little more convenient; and rituximab IV is much more convenient.	After Cycle 8 of induction treatment (24 weeks) and during the maintenance part of the study after 12 months (i.e., Cycle 15), and after the end of the maintenance treatment, (i.e., Cycle 20) (1 Cycle=4 weeks for Cycle 8 and 8 weeks for Cycles 15 and 20)