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

NCT ID: NCT01200758

Last Updated: 2018-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-15
• Study Completion Date: 2017-10-31

Brief 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.

Conditions

Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stage I and II: Rituximab IV + Chemotherapy (CHOP/CVP)

Eight cycles of rituximab IV infusion (375 mg/m\^2; rituximab induction) in combination with up to 8 cycles of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) or cyclophosphamide, vincristine, prednisolone (CVP) chemotherapy (as per institutional practice) 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.

Group Type: ACTIVE_COMPARATOR

Rituximab IV

Intervention Type: DRUG

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

Intervention Type: DRUG

Eight cycles of cyclophosphamide (750 mg/m\^2 IV) administered every 3 weeks.

Doxorubicin

Intervention Type: DRUG

Eight cycles of doxorubicin (50 mg/m\^2 IV) administered every 3 weeks.

Vincristine

Intervention Type: DRUG

Eight cycles of doxorubicin (1.4 mg/m\^2 IV) administered every 3 weeks.

Prednisone/Prednisolone

Intervention Type: DRUG

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.

Stage I and II: Rituximab SC + Chemotherapy (CHOP/CVP)

First cycle of rituximab IV infusion (375 mg/m\^2) + 7 cycles of rituximab SC (1400 mg; rituximab induction) in combination with up to 8 cycles of CHOP or CVP chemotherapy (as per institutional practice) administered every 3 weeks. Participants achieving at least PR entered rituximab SC (1400 mg) maintenance therapy once every 8 weeks for 24 months.

Group Type: EXPERIMENTAL

Rituximab SC

Intervention Type: DRUG

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.

Cyclophosphamide

Intervention Type: DRUG

Eight cycles of cyclophosphamide (750 mg/m\^2 IV) administered every 3 weeks.

Doxorubicin

Intervention Type: DRUG

Eight cycles of doxorubicin (50 mg/m\^2 IV) administered every 3 weeks.

Vincristine

Intervention Type: DRUG

Eight cycles of doxorubicin (1.4 mg/m\^2 IV) administered every 3 weeks.

Prednisone/Prednisolone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Cyclophosphamide

Eight cycles of cyclophosphamide (750 mg/m\^2 IV) administered every 3 weeks.

Intervention Type: DRUG

Doxorubicin

Eight cycles of doxorubicin (50 mg/m\^2 IV) administered every 3 weeks.

Intervention Type: DRUG

Vincristine

Eight cycles of doxorubicin (1.4 mg/m\^2 IV) administered every 3 weeks.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

MabThera; MabThera

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Gosford Hospital; Cancer Care Services

Gosford, New South Wales, Australia

Wollongong Hospital; Cancer Services

Wollongong, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Gold Coast Hospital; Haematology Department

Southport, Queensland, Australia

Queen Elizabeth Hospital; Haematology

Woodville South, South Australia, Australia

UZ Antwerpen

Edegem, , Belgium

CHU Sart-Tilman

Liège, , Belgium

Sint Augustinus Wilrijk

Wilrijk, , Belgium

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, , Bosnia and Herzegovina

Nucleo de Hematologia e Transplante de Medula Ossea de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Santa Casa de Misericordia de Sao Paulo; Hematologia e Hemoterapia

São Paulo, São Paulo, Brazil

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, Brazil

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, , Bulgaria

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada

Cite de La Sante de Laval; Hemato-Oncologie

Laval, 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-Rivières, Quebec, Canada

CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie

Québec, , Canada

Fundacion Cardioinfantil

Bogotá, , Colombia

Centro Medico Imbanaco

Cali, , Colombia

Hospital Pablo Tobon Uribe

Medellin-Antioquia, , Colombia

Oncólogos de Occidente

Pereira, , Colombia

UHC Rijeka

Rijeka, , Croatia

University Hospital Center Zagreb; Haematology Department

Zagreb, , Croatia

Aarhus Universitetshospital, Hæmatologisk Afdeling R

Aarhus, , 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, , Denmark

Helsinki University Central Hospital; Dept of Oncology

Helsinki, , Finland

Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie

Bordeaux, , France

Hopital Henri Mondor; Hematologie Clinique

Créteil, , 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-Bénite, , France

Hopital De La Miletrie; Hematologie Et Oncologie Medicale

Poitiers, , France

Hopital Bretonneau; Hematologie Therapie Cellulaire

Tours, , France

M.Zodelava's Hematology Center

Tbilisi, , Georgia

Mediclub

Tbilisi, , Georgia

Institute of Hematology and Transfusiology

Tbilisi, , Georgia

Chemotherapy and Immunotherapy Clinic Medulla

Tbilisi, , Georgia

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Gemeinschaftspraxis PD Dr. med. Marcel Reiser und Dr. med. Ildiko Kátay

Cologne, , 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

Hanover, , Germany

St. Vincentius Kliniken Ag; Medizinische Klinik Abt. 2

Karlsruhe, , Germany

UKSH Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie

Kiel, , 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

Saarbrücken, , Germany

Praxis für Hämatologie & Onkologie

Saarbrücken, , Germany

Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine

Athens, , Greece

Attiko Hospital; Haematology Clinic

Athens, , Greece

IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo

San Giovanni Rotondo, Apulia, Italy

Azienda Ospedaliera Ospedale S.Carlo; Ematologia

Potenza, Basilicate, Italy

A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica

Napoli, Campania, Italy

AUSL - IRCCS Santa Maria Nuova; U.O. Day Hospital di Oncologia

Reggio Emilia, Emilia-Romagna, Italy

Ospedale S. Eugenio; Divisione Di Ematologia

Rome, Lazio, Italy

Uni Degli Studi Di Genova; 1A Divisione Di Ematologia

Genoa, Liguria, Italy

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia

Brescia, Lombardy, Italy

Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia

Milan, Lombardy, Italy

Ospedale Ca Foncello; Ematologia

Treviso, Veneto, Italy

Ospedale Di Vicenza; Nefrologia, Ematologia

Vicenza, Veneto, Italy

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, Sarawak, Malaysia

Ampang Hospital; Department of Haematology

Ampang, , Malaysia

Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre

Chihuahua City, , Mexico

Hospital General De Culiacan; Servicio De Hematologia

Culiacán, , Mexico

Hospital Universitario Dr. Jose E. Gonzalez; Haematology

Monterrey, , Mexico

Centro de Estudios Clinicos de Queretaro (CECLIQ)

Querétaro, , Mexico

Canterbury Health Laboratories; Haematology

Christchurch, , New Zealand

Palmerston North Hospital; Regional Cancer Treatment Service

Palmerston North, , New Zealand

University Clinic for Hematology; HSCT Department

Skopje, , North Macedonia

University Clinic of Hematology Skopje, Hospital Care Department

Skopje, , North Macedonia

Instituto;Oncologico Miraflores

Lima, , Peru

Oncosalud Sac; Oncología

Lima, , Peru

Hospital Maria Auxiliadora

Lima, , Peru

Spitalul Clinic Judetean de Urgenta Brasov,Clinica de Hematologie

Brasov, , Romania

Fundeni Clinical Inst. ; Hematology Dept

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Sf. Spiridon Iasi, Clinica de Hematologie

Iași, , Romania

Institutul Regional de Oncologie Iasi; Clinica de Hematologie

Iași, , Romania

Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie

Târgu Mureş, , Romania

Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie

Timișoara, , Romania

Clinical Oncology Dispensary of Ministry of Health of Tatarstan

Kazan', , Russia

N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis

Moscow, , Russia

Haematology Research Center; Haematology

Moscow, , Russia

Penza Regional Oncology Dispensary

Penza, , Russia

Research Inst. of Hematology & Blood Transfusion ; Hematology

Saint Petersburg, , Russia

St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta

Saint Petersburg, , Russia

Russian Scientific Center of Radiology and Surgical Technologies; Dept of Radiology

St.Petersburg, Pesochny, , Russia

Institute of Hematology

Belgrade, , Serbia

Clinical Center Vojvodine; Clinic for Hematology

Novi Sad, , Serbia

National University Hospital; National University Cancer Institute, Singapore (NCIS)

Singapore, , Singapore

Singapore General Hospital; Department of Haematology

Singapore, , Singapore

National Cancer Centre; Medical Oncology

Singapore, , Singapore

St. Elisabeths Cancer Center

Bratislava, , Slovakia

National Cancer Inst. ; Dept. of Chemotherapy

Bratislava, , Slovakia

National Hospital; Oncotherapy Dept

Bloemfontein, , South Africa

Durban Oncology Center

Durban, , South Africa

University of Witwatersrand/Johannesburg Hospital; Dept. of ocnology

Johannesburg, , South Africa

Cancercare

Kraaifontein, , South Africa

King Edward VIII; Department of Haematology

KwaKhangela, , South Africa

Hospital Universitario Puerta del Mar; Servicio de Hematologia

Cadiz, Cadiz, Spain

Hospital del Mar; Servicio de Hematologia

Barcelona, , Spain

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, , Spain

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, , Spain

Hospital Duran i Reynals; Servicio de Hematologia

Barcelona, , Spain

Hospital Universitario de la Princesa; Servicio de Hematologia

Madrid, , Spain

Hospital Ramon y Cajal; 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

Seville, , Spain

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, , Spain

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, , Thailand

Adana Baskent University Hospital; Medical Oncology

Adana, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty; Hematology Department

Istanbul, , Turkey (Türkiye)

Bilim University School of Medicine; Hematology

Istanbul, , Turkey (Türkiye)

Dokuz Eylul Uni ; Hematology

Izmir, , Turkey (Türkiye)

Ege Uni Medical School; Hematology

Izmir, , Turkey (Türkiye)

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, , United Kingdom

Countries

Australia; Belgium; Bosnia and Herzegovina; Brazil; Bulgaria; Canada; Colombia; Croatia; Denmark; Finland; France; Georgia; Germany; Greece; Italy; Malaysia; Mexico; New Zealand; North Macedonia; Peru; Romania; Russia; Serbia; Singapore; Slovakia; South Africa; Spain; Thailand; Turkey (Türkiye); United Kingdom

References

Davies A, Merli F, Mihaljevic B, Mercadal S, Siritanaratkul N, Solal-Celigny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. doi: 10.1016/S2352-3026(17)30078-9. Epub 2017 May 2.

Reference Type: DERIVED

PMID: 28476440 (View on PubMed)

Davies A, Merli F, Mihaljevic B, Siritanaratkul N, Solal-Celigny P, Barrett M, Berge C, Bittner B, Boehnke A, McIntyre C, Macdonald D. Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study. Lancet Oncol. 2014 Mar;15(3):343-52. doi: 10.1016/S1470-2045(14)70005-1. Epub 2014 Feb 10.

Reference Type: DERIVED

PMID: 24521993 (View on PubMed)

Mao CP, Brovarney MR, Dabbagh K, Birnbock HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.

Reference Type: DERIVED

PMID: 24265828 (View on PubMed)

Shpilberg O, Jackisch C. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer. 2013 Sep 17;109(6):1556-61. doi: 10.1038/bjc.2013.371. Epub 2013 Sep 3.

Reference Type: DERIVED

PMID: 24002601 (View on PubMed)

Other Identifiers

2010-021377-36

Identifier Type: -

Identifier Source: secondary_id

BO22334

Identifier Type: -

Identifier Source: org_study_id