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 (MabCute)

A Randomized Study Comparing Maintenance Therapy With Subcutaneous Rituximab Continued Until Progression With Observation Only in Patients With Relapsed or Refractory, Indolent Non-Hodgkin's Lymphoma Who Completed and Responded to Rituximab-based Immunochemotherapy Induction and Initial 2-year Rituximab Maintenance Therapy Administered Subcutaneously

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.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Chemotherapy (Induction Period); Drug: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 692
• Phase: Phase 3

Contacts and Locations

Study Locations

• Albania
  • Tirana, Albania, 1000
    • University "Mother Theresa" Hospital Center; Oncology Department
• Argentina
  • Buenos Aires, Argentina, 1431
    • CEMIC Saavedra
  • Cordoba, Argentina, X5003DCE
    • Instituto Damic
  • Mar Del Plata, Argentina, 7600
    • Hospital Privado de Comunidad; Oncology
• Austria
  • Graz, Austria, 8036
    • Lkh-Univ. Klinikum Graz; Klin. Abt. Für Hämatologie
  • Innsbruck, Austria, 6020
    • Tiroler Landeskrankenanstalten Ges.M.B.H.; Innere Medizin Abt. Für Hämatologie & Onkologie
  • Linz, Austria, 4020
    • Kepler Universitätskliniken GmbH - Med Campus III; III. Medizinische Abteilung
  • Rankweil, Austria, 6830
    • Landeskrankenhaus Rankweil; Interne E
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie
• Brazil
  • RJ
    • Rio de janeiro, RJ, Brazil, 22250-906
      • Centro de Tratamento Oncologico - CETRON
  • RS
    • Passo Fundo, RS, Brazil, 99010-260
      • Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
    • Porto Alegre, RS, Brazil, 90035-003
      • Hospital das Clinicas - UFRGS
  • SC
    • Florianopolis, SC, Brazil, 88034-000
      • Centro de Pesquisas Oncológicas - CEPON
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Hospital de Cancer de Barretos
    • Sao Paulo, SP, Brazil, 01236-030
      • Instituto de Ensino e Pesquisa Sao Lucas - IEP
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP; Hematologia
    • Sao Paulo, SP, Brazil, 08270-070
      • Hospital Santa Marcelina;Oncologia
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Dr Georgi Stranski; Hematology
  • Sofia, Bulgaria, 1431
    • UMHAT Alexandrovska EAD; Hematology
  • Sofia, Bulgaria, 1407
    • Tokuda Hospital Sofia; Hematology department
• Colombia
  • Bogota, Colombia
    • Centro Javeriano de Oncología
  • Bogota, Colombia
    • Fundacion Santa Fe de Bogota
  • Bogota, Colombia
    • Instituto Nacional de Cancerologia; Hematology
• Ecuador
  • Guayaquil, Ecuador, EC090150
    • Teodoro Maldonado Carbo Hospital; Oncology Service
  • Guayaquil, Ecuador, EC090104
    • Hospital Abel Gilbert Ponton; Oncology
  • Portoviejo, Ecuador, EC130104
    • Hospital Solca Portoviejo; Oncologia
  • Quito, Ecuador, EC170124
    • Hospital Solca Quito; Oncologia
• Egypt
  • Cairo, Egypt, 11562
    • Kasr Eieny Uni Hospital; Oncology (Nemrock)
• France
  • Angers Cedex 9, France, 49933
    • Centre Hospitalier Uni Ire; Service Des Maladies Du Sang
  • Aurillac, France, 15000
    • CH Henri Mondor; Med Interne Neuro Endocrinologie
  • Bayonne, France, 64109
    • Centre Hospitalier de La Cote Basque; Hematologie
  • Besancon, France, 25030
    • Hopital Jean Minjoz; Hematologie
  • Brest, France, 29609
    • Hopital Augustin Morvan; Hematologie
  • CHAMBERY Cedex, France, 73011
    • CH Metropole de Savoie
  • Caen, France, 14000
    • Institut d'Hématologie de Basse Normandie
  • Clermont Ferrand, France, 63003
    • Chu Estaing; Hematologie Clinique Adultes
  • Corbeil Essonnes, France, 91000
    • Ch Sud Francilien; Hematologie Oncologie
  • Creteil, France, 94010
    • Hopital Henri Mondor
  • Dijon, France, 21079
    • Chu Site Du Bocage;Hematologie Clinique
  • La Roche Sur Yon, France, 85925
    • Centre Hospitalier Départemental Les Oudairies
  • La Tronche, France, 38700
    • Hôpital Albert Michallon; Hematologie Clinique
  • Le Chesnay, France, 78157
    • Hopital Andre Mignot; Hematologie - Oncologie
  • Le Mans, France, 72037
    • Ch Du Mans; Medecine Hematologie Oncologie
  • Lille, France, 59037
    • Hopital Claude Huriez; Hematologie
  • Limoges, France, 87042
    • Hopital Uni Ire Dupuytren; Hematologie
  • Marseille, France, 13015
    • Hopital Nord; Laboratoire D'Hematologie
  • Montpellier, France, 34295
    • Hôpital Lapeyronie; Hématologie Oncologie Médicale
  • Mulhouse, France, 68070
    • Hopital Emile Muller; Hematologie
  • Nantes, France, 44093
    • Hopital Hotel Dieu Et Hme; Clinique Dermatologique
  • Nice, France, 06189
    • Centre Antoine Lacassagne;B4 Hematologie Cancerologie
  • Paris, France, 75651
    • Hopital Pitie Salpetriere; Hematologie Clinique
  • Pessac, France, 33604
    • Hopital De Haut Leveque; Hematologie Clinique
  • Rouen, France, 76038
    • Centre Henri Becquerel; Hematologie
  • Toulouse, France, 31059
    • Hopital Purpan; Hematologie Clinique
• Germany
  • Bochum, Germany, 44787
    • Gemeinschaftspraxis Dr. Bueckner und Dr. Nueckel
  • Darmstadt, Germany, 64283
    • Klinikum Darmstadt GmbH; Med. Klinik V; Onkologie & Hämatologie
  • Dortmund, Germany, 44137
    • St. Johannes Hospital; Abt. für Hämatologie und Onkologie
  • Dresden, Germany, 01307
    • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
  • Dresden, Germany, 01307
    • Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex; Fachaerzte fuer Innere Medizin
  • Greifswald, Germany, 17475
    • Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
  • Halle, Germany, 06110
    • Internistisch-Onkologische Gemeinschaftspraxis; Dres. Rohrberg, Hurtz, Schma usw.
  • Hamburg, Germany, 22081
    • OncoResearch Lerchenfeld GmbH
  • Jena, Germany, 07743
    • Onkologische Schwerpunktpraxis (Eps-Gmbh)
  • Kaiserslautern, Germany, 67655
    • Dres. Richard Hansen Susanne Pfitzner-Dempfle und Manfred Reeb
  • Lehrte, Germany, 31275
    • Dres. Barbara Tschechne Stefanie Luft und Wolf-Oliver Jordan
  • Lübeck, Germany, 23562
    • Onkologische Schwerpunktpraxis Lübeck
  • Magdeburg, Germany, 39104
    • Onkologische Gemeinschaftspraxis
  • Marburg, Germany, 35037
    • Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach
  • Mayen, Germany, 56727
    • Dres. Michael Maasberg Marion Schmitz und Maria Theresia Keller
  • Muenchen, Germany, 81377
    • Klinikum Grosshadern der LMU
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)
  • München, Germany, 80804
    • Staedtisches Krankenhaus Muenchen-Schwabing, Haematologie & Onkolgie
  • München, Germany, 81241
    • Hamatol Onkol Praxisgemeinschaft Dres H H-D Schick/D Schick
  • Naunhof, Germany, 04683
    • Praxis Dr.med. Jens Uhlig
  • Recklinghausen, Germany, 45659
    • Oncologianova GmbH
  • Regensburg, Germany, 93053
    • Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale
  • Rostock, Germany, 18107
    • Dres. Andreas Hübner, Andreas Lück und Petra Bruhn
  • Singen, Germany, 78224
    • Dres. Ulrich Banhardt und Thomas Fietz
  • Stuttgart, Germany, 70190
    • Dres. Emil Höring Matthias Respondek und Ulrike Schwinger
• Greece
  • Athens, Greece, 106 76
    • General Hospital of Athens Evangelismos; Hematology
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine
  • Ioannina, Greece, 455 00
    • University Hospital of Ioannina; Hematology
  • Larissa, Greece, 411100
    • University Hospital of Larissa; Hematology Dept.
  • Patras, Greece, 265 00
    • University Hospital Of Patras; Dept. Of Internal Medicine-Hematology Division
• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncology, A Dept of Internal Medicine
  • Budapest, Hungary, 1083
    • Semmelweis University, First Dept of Medicine
  • Budapest, Hungary, 1097
    • St Laszlo Hospital, Pharmacy
  • Debrecen, Hungary, 4004
    • Uni of Debrecen; 2Nd Clinic of Internal Medicine
  • Pecs, Hungary, 7624
    • University of Pecs, I st Dept of Internal Medicine
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
    • Napoli, Campania, Italy, 80131
      • Ospedale Cardarelli; Divisione Di Ematologia
    • Napoli, Campania, Italy, 80131
      • A.O. Universitaria Federico II Di Napoli; Oncologia Ed Endocrinologia Clinica
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O.U. Policlinico di Modena-Dipartimento di Medicina Diagnostica, Clinica e di Sanità pubblica
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
  • Liguria
    • Genova, Liguria, Italy, 16132
      • A.O. Universitaria S. Martino Di Genova; Ematologia 1
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
    • Milano, Lombardia, Italy, 20162
      • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
  • Puglia
    • Bari, Puglia, Italy, 70124
      • Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
  • Sicilia
    • Via S. Sofia 78, Sicilia, Italy, 95123
      • Ospedale Ferrarotto; Divisione Di Ematologia
  • Toscana
    • Firenze, Toscana, Italy, 50135
      • Az. Osp. Di Careggi; Divisione Di Ematologia
    • Pisa, Toscana, Italy, 56100
      • Ospedale Santa Chiara; Unita Operativa Di Ematologia
    • Siena, Toscana, Italy, 53100
      • A.O. Universitaria Senese; Ematologia
  • Trentino-Alto Adige
    • Bolzano, Trentino-Alto Adige, Italy, 39100
      • Azienda Sanitaria Di Bolzano; Ematologia E Centro Trapianto Mid.Osseo
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia
    • Treviso, Veneto, Italy, 31100
      • Ospedale Ca Foncello; Ematologia
    • Verona, Veneto, Italy, 37130
      • Uni Di Verona Policlinico G.B. Rossi; Divisione E Cattedra Di Ematologia
• Lithuania
  • Klaipeda, Lithuania, 92288
    • Seamen' Hospital' Dept. of haematology
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssykehus
  • Oslo, Norway, 0310
    • Oslo Universitetssykehus HF; Radiumhospitalet
  • Stavanger, Norway, 4011
    • Helse Stavanger HF, Stavanger Universitetssjukehus; Klinikk for Blod og kreftsykdommer
  • Trondheim, Norway, 7030
    • St. Olavs Hospital HF, Kreftavdelingen, Gastrosentret
• Romania
  • Brasov, Romania, 500152
    • Policlinica de Diagnostic Rapid
  • Brasov, Romania, 500360
    • County Clinical Emergency Hospital Brasov
  • Bucharest, Romania, 022338
    • Institutul Clinic Fundeni; Hematologie
  • Bucuresti, Romania, 030171
    • Spitalul Clinic Coltea; Clinica de Hematologie
  • Targu-mures, Romania, 540136
    • Spitalul Clinic Judetean de Urgenta Targu-Mures; compartiment Hematologie
  • Timisoara, Romania, 300079
    • Spitalul Clinic municipal de Urgenta Timisoara; Clinica de Hematologie
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Regional Oncology Center
  • Moscow, Russian Federation, 125101
    • City Clin Hosp n.a. S.P.Botkin
  • Moscow, Russian Federation, 115478
    • N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
  • Moscow, Russian Federation, 123995
    • Rus Med Academy for Postgraduate Education; Oncology Department
  • Nizhny Novgorod, Russian Federation, 603126
    • Regional Clinical Hospital N.A. Semashko; Hematology
  • St Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital
  • St Petersburg, Russian Federation, 197758
    • Petrov Research Inst. of Oncology
  • St. Petersburg, Russian Federation, 191024
    • SRI of Hematology and Transfusiology
• Slovakia
  • Bratislava, Slovakia, 833 10
    • National Oncology Inst. ; Dept. of Haematology
  • Martin, Slovakia, 036 59
    • Uni Hospital ; Dept. of Haematol. & Transfusion Medicine
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute of Oncology Ljubljana
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Hematologia
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
  • Barcelona, Spain, 08907
    • Hospital Duran i Reynals; Servicio de Hematologia
  • Caceres, Spain, 10003
    • Hospital San Pedro de Alcantara; Servicio de Hematología
  • Granada, Spain, 18003
    • Hospital Universitario San Cecilio; Servicio de Oncologia
  • Jaen, Spain, 23007
    • Complejo Hospitalario de Jaen- Hospital Universitario Medico Quirurgico; Servicio de Hematologia
  • Madrid, Spain, 28050
    • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Hematologia
  • Orense, Spain, 32005
    • Complejo Hospitalario Universitario de Ourense, Servicio de Hematologia
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia
  • Zamora, Spain, 49002
    • Complejo Hospitalario Zamora- H. Virgen de la Concha; Servicio de Hematología
  • Zaragoza, Spain, 50015
    • Hospital Royo Villanova; Servicio de Hematologia
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche; Servicio de Oncologia
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Univ. Central de Asturias; servicio de Hematologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
      • Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
  • Cadiz
    • Jerez de La Frontera, Cadiz, Spain, 11407
      • Hospital de Jerez de la Frontera; Servicio de Hematologia
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07014
      • Hospital Universitario Son Espases
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Hematologia
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias;servicio de Oncologia
    • La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias;servicio de Hematologia
• Sweden
  • Halmstad, Sweden, 30185
    • Laenssjukhuset; Medicinkliniken/Hematologsektionen
  • Luleå, Sweden, S-971 80
    • Sunderby Sjukhus; Medicinkliniken
  • Stockholm, Sweden, 112 81
    • Capio, S:T Gorans Hospital; Dept of Medicine
  • Stockholm, Sweden, 118 83
    • Södersjukhuset, Medicinkliniken/Sektionen för Hematologi
  • Uddevalla, Sweden, 45180
    • Uddevalla Sjukhus; Medicinkliniken
  • Västerås, Sweden, 72189
    • Västmanlands sjukhus Västerås, Onkologmottagningen
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Ospedale San Giovanni; Oncologia
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe Uni Medical Faculty; Hematology
  • Ankara, Turkey, 06500
    • Gazi Uni Medical School; Hematology
  • Ankara, Turkey, 06010
    • GATA (Gulhane Military Medical School)
  • Istanbul, Turkey, 34093
    • Istanbul Uni Capa Medical Faculty; Inst. of Oncology
  • Istanbul, Turkey, 34300
    • Marmara University Pendik Training and Research Hospital, Hematology Department
  • Kayseri, Turkey, 38039
    • Erciyes Uni ; Hematology
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital; Department of Haematology
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth General Hospital; Haematology
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Hospital; Haematology
  • Canterbury, United Kingdom, CT1 3NG
    • Kent & Canterbury Hospital; Clinical Haematology
  • Cardiff, United Kingdom, CF14 4XW
    • Uni Hospital of Wales; Dept of Haematology
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary; Dept of Haematology
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool Uni Hospital; Haematology
  • London, United Kingdom, SW3 5PT
    • The Royal Marsden Hospital; Dept of Medicine
  • London, United Kingdom, NW1 2PG
    • University College London, Department of Haematology
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk & Norwich Hospital; Dept of Haematology
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital; Dept of Haematology
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital; Oxford Cancer and Haematology Centre
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital; Haematology
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept. of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.	Drug: 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.; Drug: Rituximab; Participants will receive rituximab according to the regimen specified in individual arm.; Other Names: Rituxan; MabThera; RO0452294
Experimental: 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).	Drug: 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.; Drug: Rituximab; Participants will receive rituximab according to the regimen specified in individual arm.; Other Names: Rituxan; MabThera; RO0452294

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance II: Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia	Progression free survival from randomization (PFSrand) is defined as the time from date of randomization to the date of first documented disease progression or death, whichever occurs first. One participant died in Induction before randomization and one participant died in Maintenance II Observation arm due to an SAE and were not considered in the analysis as no death page was completed. The Observation arm did not include one participant with AE outcome of death reported retrospectively 2 months after discontinuation from study (censored as having no event on Day 456 post-randomization).	From randomization (Maintenance II) up to disease progression or death, whichever occurs first (up to approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious AEs, and Infusion/Administration-related Reactions (IRRs/ARRs)	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Not all AEs were followed up for the randomized Observation arm. Only Serious AEs and AE grade 3-5 (obtained retrospectively) were collected for this arm. Therefore arms are not comparable overall.	From day of first rituximab induction dose up to day of disease progression, or discontinuation of treatment for any reason (up to approximately 87 months)
Event-free Survival (Time to Treatment Failure) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia	Event-Free Survival was measured from the day of first rituximab Induction dose through Maintenance I and Maintenance II rituximab arm until the date of any treatment failure, including disease progression, or discontinuation of treatment for any reason (e.g. disease progression, toxicity, patient preference, initiation of new anti-lymphoma treatment, or death). Treatment discontinuation was considered as an event and was not applicable to the randomized observation arm.	From day of first rituximab induction dose up to day of any treatment failure, including disease progression, or discontinuation of treatment for any reason (up to approximately 87 months)
Time to Next Lymphoma Treatment (TNLT)	Time to next lymphoma treatment (TNLT) is defined as the time from date of first rituximab induction dose to the date date of first documented intake of any new antilymphoma treatment (chemotherapy, radiotherapy, immunotherapy, etc.).	From day of first rituximab induction dose up to any new lymphoma treatment (up to approximately 87 months)
Overall Survival	Overall survival from first induction treatment (OSRegist) is defined as the time from date of first rituximab induction dose to the date of death, irrespective of cause. One participant died in Induction before randomization and one participant died in Maintenance II Observation arm due to an SAE and were not considered in the analysis as no death page was completed.	From day of first rituximab induction dose up to death (up to approximately 87 months)
Maintenance II: Overall Survival	Overall survival from randomization (OSrand) is defined as the time from date of randomization to the date of death, irrespective of cause.	From randomization (Maintenance II) up to death (up to approximately 24 months)
Percentage of Participants With Partial or Complete Tumor Response (PR/CR) Assessment at End of Induction Using 1999 International Working Group Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia	Overall response rate is defined as the proportion of responders at the end of the Induction period. A responder is defined as a participant experiencing either CR or PR tumor response according to the Cheson response criteria for indolent lymphoma or the recommendations for Waldenström's macroglobulinemia.	From day of first rituximab induction dose up to end of induction period (up to approximately 8 months)
Maintenance I: Percentage of Participants With Conversion of PR to CR Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia		From day of first rituximab induction dose up to end of Maintenance I period (up to approximately 32 months)
Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia	Progression free survival from first induction treatment (PFSregist) is defined as the time from date of first rituximab induction dose to the date of first documented disease progression or death by any cause, whichever occurs first.	From day of first rituximab induction dose up to disease progression or death, whichever occurs first (up to approximately 87 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2011
• Primary Completion (Actual): June 2, 2018
• Study Completion (Actual): June 2, 2018

Study Registration Dates

• First Submitted: October 19, 2011
• First Submitted That Met QC Criteria: October 26, 2011
• First Posted (Estimate): October 28, 2011

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: MO25455; 2010-023407-95 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes