A Study Comparing Maintenance Subcutaneous Rituximab With Observation Only in Participants With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma Who Had Responded to Rituximab-based Immunochemotherapy Induction and 2-year Maintenance With Subcutaneous Rituximab

NCT ID: NCT01461928

Last Updated: 2019-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 692 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-20
• Study Completion Date: 2018-06-02

Brief Summary

This multicenter, randomized, open-label, parallel-group study will evaluate the efficacy and safety of subcutaneously administered rituximab in comparison with observation only as maintenance therapy in participants with relapsed or refractory indolent Non-Hodgkin's lymphoma (NHL). All participants will receive induction therapy with rituximab (375 milligrams per square meter [mg/m^2] intravenously [IV] in Cycle 1, then 1400 mg subcutaneous [SC] every 3-4 weeks) plus standard chemotherapy for 6-8 months; followed by 24 months of maintenance I period with rituximab (1400 mg SC every 8 weeks). Participants completing therapy and showing partial or complete response will be randomized to receive either rituximab (1400 mg SC every 8 weeks) or observation with no treatment during maintenance II period and will be followed for at least 15 months. Anticipated time on study treatment is until disease progression, unacceptable toxicity or end of study, whichever occurs first.

Conditions

Non-Hodgkin's Lymphoma

Study Design

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

Study Groups

Maintenance II Period Observation Only

Participants will receive standard chemotherapy regimen in combination with 375 mg/m\^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); no treatment in Maintenance II period until disease progression or end of study, whichever occurs first.

Group Type: OTHER

Chemotherapy (Induction Period)

Intervention Type: DRUG

Participants will receive standard combination chemotherapy every 3-4 weeks for 6 to 8 months. The chemotherapy regimen will be selected at Investigator's discretion, for individual participant. Study protocol does not enforce any particular chemotherapy regimen.

Rituximab

Intervention Type: DRUG

Participants will receive rituximab according to the regimen specified in individual arm.

Maintenance II Period Rituximab

Participants will receive standard chemotherapy regimen in combination with 375 mg/m\^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); 1400 mg rituximab SC every 8 weeks until disease progression or end of study, whichever occurs first (Maintenance II period).

Group Type: EXPERIMENTAL

Chemotherapy (Induction Period)

Intervention Type: DRUG

Participants will receive standard combination chemotherapy every 3-4 weeks for 6 to 8 months. The chemotherapy regimen will be selected at Investigator's discretion, for individual participant. Study protocol does not enforce any particular chemotherapy regimen.

Rituximab

Intervention Type: DRUG

Participants will receive rituximab according to the regimen specified in individual arm.

Interventions

Chemotherapy (Induction Period)

Participants will receive standard combination chemotherapy every 3-4 weeks for 6 to 8 months. The chemotherapy regimen will be selected at Investigator's discretion, for individual participant. Study protocol does not enforce any particular chemotherapy regimen.

Intervention Type: DRUG

Rituximab

Participants will receive rituximab according to the regimen specified in individual arm.

Intervention Type: DRUG

Other Intervention Names

Rituxan; MabThera; RO0452294

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed Cluster of Differentiation 20-positive (CD20+) follicular NHL Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström's macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma) according to World Health Organization (WHO) classification system
• Participants must have received and must have relapsed or been refractory to, one or more lines of adequate therapy prior to enrollment, including at least one line consisting of immunotherapy and/or chemotherapy and/or radiotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2

Exclusion Criteria

• Transformation to high-grade lymphoma
• Aggressive lymphoma (for example, mantle cell lymphoma [MCL])
• Presence or history of central nervous system (CNS) lymphomatous disease
• Other malignancy within 5 years prior to enrollment, except for curatively treated carcinoma in situ of the cervix, squamous cell carcinoma of the skin or basal cell skin cancer, or cervical carcinoma Stage 1B or less, breast cancer in situ or localized prostate cancer Stage T1c if treated with curative intent and relapse- and metastasis-free for at least 2 years prior to enrollment
• Inadequate hematological, hepatic or renal function
• Known human immunodeficiency virus (HIV) infection
• Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B or C)
• Pregnant or breastfeeding women

• 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

Ch Du Mans; Medecine Hematologie Oncologie

Le Mans, , France

Hopital Claude Huriez; Hematologie

Lille, , France

Hopital Uni Ire Dupuytren; Hematologie

Limoges, , France

Hôpital Albert Michallon; Hematologie Clinique

La Tronche, , France

Hopital Andre Mignot; Hematologie - Oncologie

Le Chesnay, , France

University "Mother Theresa" Hospital Center; Oncology Department

Tirana, , Albania

CEMIC Saavedra

Buenos Aires, , Argentina

Instituto Damic

Córdoba, , Argentina

Hospital Privado de Comunidad; Oncology

Mar del Plata, , Argentina

Lkh-Univ. Klinikum Graz; Klin. Abt. Für Hämatologie

Graz, , Austria

Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie

Innsbruck, , Austria

Kepler Universitätskliniken GmbH - Med Campus III; III. Medizinische Abteilung

Linz, , Austria

Landeskrankenhaus Rankweil; Interne E

Rankweil, , Austria

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie

Vienna, , Austria

Centro de Tratamento Oncologico - CETRON

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia

Passo Fundo, Rio Grande do Sul, Brazil

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Centro de Pesquisas Oncologicas - CEPON

Florianópolis, Santa Catarina, Brazil

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Instituto de Ensino e Pesquisa Sao Lucas - IEP

São Paulo, São Paulo, Brazil

Hospital das Clinicas - FMUSP; Hematologia

São Paulo, São Paulo, Brazil

Hospital Santa Marcelina;Oncologia

São Paulo, São Paulo, Brazil

UMHAT Dr Georgi Stranski; Hematology

Pleven, , Bulgaria

Tokuda Hospital Sofia; Hematology department

Sofia, , Bulgaria

UMHAT Alexandrovska EAD; Hematology

Sofia, , Bulgaria

Centro Javeriano de Oncología

Bogotá, , Colombia

Fundacion Santa Fe de Bogotá

Bogotá, , Colombia

Instituto Nacional de Cancerologia; Hematology

Bogotá, , Colombia

Hospital Abel Gilbert Ponton; Oncology

Guayaquil, , Ecuador

Teodoro Maldonado Carbo Hospital; Oncology Service

Guayaquil, , Ecuador

Hospital Solca Portoviejo; Oncologia

Portoviejo, , Ecuador

Hospital Solca Quito; Oncologia

Quito, , Ecuador

Kasr Eieny Uni Hospital; Oncology (Nemrock)

Cairo, , Egypt

Centre Hospitalier Uni Ire; Service Des Maladies Du Sang

Angers, , France

CH Henri Mondor; Med Interne Neuro Endocrinologie

Aurillac, , France

Centre Hospitalier de La Cote Basque; Hematologie

Bayonne, , France

Hopital Jean Minjoz; Hematologie

Besançon, , France

Hopital Augustin Morvan; Hematologie

Brest, , France

Institut d'Hématologie de Basse Normandie

Caen, , France

CH Metropole de Savoie

Chambéry, , France

Chu Estaing; Hematologie Clinique Adultes

Clermont-Ferrand, , France

Ch Sud Francilien; Hematologie Oncologie

Corbeil-Essonnes, , France

Hopital Henri Mondor

Créteil, , France

Chu Site Du Bocage;Hematologie Clinique

Dijon, , France

Centre Hospitalier Departemental Les Oudairies

La Roche-sur-Yon, , France

Hopital Nord; Laboratoire D'Hematologie

Marseille, , France

Hôpital Lapeyronie; Hématologie Oncologie Médicale

Montpellier, , France

Hopital Emile Muller; Hematologie

Mulhouse, , France

Hopital Hotel Dieu Et Hme; Clinique Dermatologique

Nantes, , France

Centre Antoine Lacassagne;B4 Hematologie Cancerologie

Nice, , France

Hopital Pitie Salpetriere; Hematologie Clinique

Paris, , France

Hopital De Haut Leveque; Hematologie Clinique

Pessac, , France

Centre Henri Becquerel; Hematologie

Rouen, , France

Hopital Purpan; Hematologie Clinique

Toulouse, , France

Gemeinschaftspraxis Dr. Bueckner und Dr. Nueckel

Bochum, , Germany

Klinikum Darmstadt GmbH; Med. Klinik V; Onkologie & Hämatologie

Darmstadt, , Germany

St. Johannes Hospital; Abt. für Hämatologie und Onkologie

Dortmund, , Germany

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, , Germany

Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex; Fachaerzte fuer Innere Medizin

Dresden, , Germany

Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik

Greifswald, , Germany

Internistisch-Onkologische Gemeinschaftspraxis; Dres. Rohrberg, Hurtz, Schma usw.

Halle, , Germany

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

Onkologische Schwerpunktpraxis (Eps-Gmbh)

Jena, , Germany

Dres. Richard Hansen Susanne Pfitzner-Dempfle und Manfred Reeb

Kaiserslautern, , Germany

Dres. Barbara Tschechne Stefanie Luft und Wolf-Oliver Jordan

Lehrte, , Germany

Onkologische Schwerpunktpraxis Lübeck

Lübeck, , Germany

Onkologische Gemeinschaftspraxis

Magdeburg, , Germany

Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach

Marburg, , Germany

Dres. Michael Maasberg Marion Schmitz und Maria Theresia Keller

Mayen, , Germany

Staedtisches Krankenhaus Muenchen-Schwabing, Haematologie & Onkolgie

München, , Germany

Hamatol Onkol Praxisgemeinschaft Dres H H-D Schick/D Schick

München, , Germany

Klinikum Grosshadern der LMU

München, , Germany

Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)

München, , Germany

Praxis Dr.med. Jens Uhlig

Naunhof, , Germany

Oncologianova GmbH

Recklinghausen, , Germany

Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale

Regensburg, , Germany

Dres. Andreas Hübner, Andreas Lück und Petra Bruhn

Rostock, , Germany

Dres. Ulrich Banhardt und Thomas Fietz

Singen, , Germany

Dres. Emil Höring Matthias Respondek und Ulrike Schwinger

Stuttgart, , Germany

General Hospital of Athens Evangelismos; Hematology

Athens, , Greece

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

Athens, , Greece

University Hospital of Ioannina; Hematology

Ioannina, , Greece

University Hospital of Larissa; Hematology Dept.

Larissa, , Greece

University Hospital Of Patras; Dept. Of Internal Medicine-Hematology Division

Pátrai, , Greece

Semmelweis University, First Dept of Medicine

Budapest, , Hungary

St Laszlo Hospital, Pharmacy

Budapest, , Hungary

National Institute of Oncology, A Dept of Internal Medicine

Budapest, , Hungary

Uni of Debrecen; 2Nd Clinic of Internal Medicine

Debrecen, , Hungary

University of Pecs, I st Dept of Internal Medicine

Pécs, , Hungary

Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica

Bari, Apulia, Italy

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

Napoli, Campania, Italy

Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica

Napoli, Campania, Italy

Ospedale Cardarelli; Divisione Di Ematologia

Napoli, Campania, Italy

A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna

Bologna, Emilia-Romagna, Italy

A.O.U. Policlinico di Modena-Dipartimento di Medicina Diagnostica, Clinica e di Sanità pubblica

Modena, Emilia-Romagna, Italy

A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica

Udine, Friuli Venezia Giulia, Italy

Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol

Rome, Lazio, Italy

A.O. Universitaria S. Martino Di Genova; Ematologia 1

Genoa, Liguria, Italy

Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora

Milan, Lombardy, Italy

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, Italy

A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1

Turin, Piedmont, Italy

Ospedale Ferrarotto; Divisione Di Ematologia

Via S. Sofia 78, Sicily, Italy

Azienda Sanitaria Di Bolzano; Ematologia E Centro Trapianto Mid.Osseo

Bolzano, Trentino-Alto Adige, Italy

Az. Osp. Di Careggi; Divisione Di Ematologia

Florence, Tuscany, Italy

Ospedale Santa Chiara; Unita Operativa Di Ematologia

Pisa, Tuscany, Italy

A.O. Universitaria Senese; Ematologia

Siena, Tuscany, Italy

Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia

Padua, Veneto, Italy

Ospedale Ca Foncello; Ematologia

Treviso, Veneto, Italy

Uni Di Verona Policlinico G.B. Rossi; Divisione E Cattedra Di Ematologia

Verona, Veneto, Italy

Seamen' Hospital' Dept. of haematology

Klaipėda, , Lithuania

Haukeland Universitetssykehus

Bergen, , Norway

Oslo Universitetssykehus HF; Radiumhospitalet

Oslo, , Norway

Helse Stavanger HF, Stavanger Universitetssjukehus; Klinikk for Blod og kreftsykdommer

Stavanger, , Norway

St. Olavs Hospital HF, Kreftavdelingen, Gastrosentret

Trondheim, , Norway

Policlinica de Diagnostic Rapid

Brasov, , Romania

County Clinical Emergency Hospital Brasov

Brasov, , Romania

Institutul Clinic Fundeni; Hematologie

Bucharest, , Romania

Spitalul Clinic Coltea; Clinica de Hematologie

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie

Târgu Mureş, , Romania

Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie

Timișoara, , Romania

Regional Oncology Center

Chelyabinsk, , Russia

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

Moscow, , Russia

Rus Med Academy for Postgraduate Education; Oncology Department

Moscow, , Russia

City Clin Hosp n.a. S.P.Botkin

Moscow, , Russia

Regional Clinical Hospital N.A. Semashko; Hematology

Nizhny Novgorod, , Russia

SRI of Hematology and Transfusiology

Saint Petersburg, , Russia

Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

Petrov Research Inst. of Oncology

Saint Petersburg, , Russia

National Oncology Inst. ; Dept. of Haematology

Bratislava, , Slovakia

Uni Hospital ; Dept. of Haematol. & Transfusion Medicine

Martin, , Slovakia

Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Hospital General Universitario de Elche; Servicio de Oncologia

Elche, Alicante, Spain

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia

Badalona, Barcelona, Spain

Hospital de Jerez de la Frontera; Servicio de Hematologia

Jerez de la Frontera, Cadiz, Spain

Hospital Quiron de Madrid; Servicio de Hematologia

Pozuelo de Alarcón, Madrid, Spain

Hospital Univ. Central de Asturias; servicio de Hematologia

Oviedo, Principality of Asturias, Spain

Hospital Universitario de Canarias;servicio de Hematologia

San Cristóbal de La Laguna, Tenerife, Spain

Hospital Universitario de Canarias;servicio de Oncologia

San Cristóbal de La Laguna, Tenerife, Spain

Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia

Barcelona, , Spain

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, , Spain

Hospital Duran i Reynals; Servicio de Hematologia

Barcelona, , Spain

Hospital San Pedro De Alcantara; Servicio de Hematologia

Cáceres, , Spain

Hospital Universitario San Cecilio; Servicio de Oncologia

Granada, , Spain

Complejo Hospitalario de Jaen- Hospital Universitario Medico Quirurgico; Servicio de Hematologia

Jaén, , Spain

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Hematologia

Málaga, , Spain

Complejo Hospitalario Universitario de Ourense, Servicio de Hematologia

Ourense, , Spain

Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia

Valencia, , Spain

Complejo Hospitalario Zamora- H. Virgen de la Concha; Servicio de Hematología

Zamora, , Spain

Hospital Royo Villanova; Servicio de Hematologia

Zaragoza, , Spain

Laenssjukhuset; Medicinkliniken/Hematologsektionen

Halmstad, , Sweden

Sunderby Sjukhus; Medicinkliniken

Luleå, , Sweden

Capio, S:T Gorans Hospital; Dept of Medicine

Stockholm, , Sweden

Södersjukhuset, Medicinkliniken/Sektionen för Hematologi

Stockholm, , Sweden

Uddevalla Sjukhus; Medicinkliniken

Uddevalla, , Sweden

Västmanlands sjukhus Västerås, Onkologmottagningen

Västerås, , Sweden

Ospedale San Giovanni; Oncologia

Bellinzona, , Switzerland

UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie

Zurich, , Switzerland

GATA (Gulhane Military Medical School)

Ankara, , Turkey (Türkiye)

Hacettepe Uni Medical Faculty; Hematology

Ankara, , Turkey (Türkiye)

Gazi Uni Medical School; Hematology

Ankara, , Turkey (Türkiye)

Istanbul Uni Capa Medical Faculty; Inst. of Oncology

Istanbul, , Turkey (Türkiye)

Marmara University Pendik Training and Research Hospital, Hematology Department

Istanbul, , Turkey (Türkiye)

Erciyes Uni ; Hematology

Kayseri, , Turkey (Türkiye)

Birmingham Heartlands Hospital; Department of Haematology

Birmingham, , United Kingdom

Royal Bournemouth General Hospital; Haematology

Bournemouth, , United Kingdom

Addenbrookes Hospital; Haematology

Cambridge, , United Kingdom

Kent & Canterbury Hospital; Clinical Haematology

Canterbury, , United Kingdom

Uni Hospital of Wales; Dept of Haematology

Cardiff, , United Kingdom

Leicester Royal Infirmary; Dept of Haematology

Leicester, , United Kingdom

Royal Liverpool Uni Hospital; Haematology

Liverpool, , United Kingdom

University College London, Department of Haematology

London, , United Kingdom

The Royal Marsden Hospital; Dept of Medicine

London, , United Kingdom

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Norfolk & Norwich Hospital; Dept of Haematology

Norwich, , United Kingdom

Nottingham City Hospital; Dept of Haematology

Nottingham, , United Kingdom

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, , United Kingdom

Derriford Hospital; Haematology

Plymouth, , United Kingdom

Royal Marsden Hospital; Dept. of Medicine

Sutton, , United Kingdom

Countries

Albania; Argentina; Austria; Brazil; Bulgaria; Colombia; Ecuador; Egypt; France; Germany; Greece; Hungary; Italy; Lithuania; Norway; Romania; Russia; Slovakia; Slovenia; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

Rule S, Barreto WG, Briones J, Carella AM, Casasnovas O, Pocock C, Wendtner CM, Zaja F, Robson S, MacGregor L, Tschopp RR, Nick S, Dreyling M. Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the phase III MabCute study. Haematologica. 2022 Feb 1;107(2):500-509. doi: 10.3324/haematol.2020.274803.

Reference Type: DERIVED

PMID: 34134469 (View on PubMed)

Theodore-Oklota C, Humphrey L, Wiesner C, Schnetzler G, Hudgens S, Campbell A. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab. Patient Prefer Adherence. 2016 Sep 13;10:1767-1776. doi: 10.2147/PPA.S108489. eCollection 2016.

Reference Type: DERIVED

PMID: 27695295 (View on PubMed)

Rule S, Collins GP, Samanta K. Subcutaneous vs intravenous rituximab in patients with non-Hodgkin lymphoma: a time and motion study in the United Kingdom. J Med Econ. 2014 Jul;17(7):459-68. doi: 10.3111/13696998.2014.914033. Epub 2014 May 7.

Reference Type: DERIVED

PMID: 24720836 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2010-023407-95

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO25455

Identifier Type: -

Identifier Source: org_study_id