A Study of Subcutaneous Versus Intravenous MabThera/Rituxan (Rituximab) in Combination With CHOP Chemotherapy in Patients With Previously Untreated CD20-Positive Diffuse Large B-Cell Lymphoma

NCT ID: NCT01649856

Last Updated: 2017-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 572 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-24
• Study Completion Date: 2016-09-16

Brief Summary

This multicenter, randomized, open label parallel-group study will evaluate the efficacy and safety of subcutaneous versus intravenous MabThera/Rituxan (rituximab) in combination with CHOP chemotherapy in patients with previously untreated CD20-positive diffuse large B-Cell lymphoma. Patients will be randomized to receive either MabThera/Rituxan 1400 mg subcutaneously or MabThera/Rituxan 375 mg/m2 intravenously on Day 1 of each cycle for 8 cycles, in combination with 6-8 cycles of CHOP chemotherapy. Anticipated time on study treatment is 6 months.

Conditions

Lymphoma, Large B-Cell, Diffuse

Study Design

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

Study Groups

A: Rituximab SC

Group Type: EXPERIMENTAL

CHOP

Intervention Type: DRUG

CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles

rituximab [MabThera/Rituxan]

Intervention Type: DRUG

The first rituximab dose will be administered intravenously on Day of Cycle 1 at a dose of 375 mg/m2. Subsequent doses of 1400 mg are administered subcutaneously on Day 1 of each cycle, for a further 7 cycles

B: Rituximab IV

Group Type: ACTIVE_COMPARATOR

CHOP

Intervention Type: DRUG

CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles

rituximab [MabThera/Rituxan]

Intervention Type: DRUG

375 mg/m2 intravenously on Day 1 of each cycle, 8 cycles

Interventions

CHOP

CHOP chemotherapy: cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone; 6 or 8 cycles

Intervention Type: DRUG

rituximab [MabThera/Rituxan]

The first rituximab dose will be administered intravenously on Day of Cycle 1 at a dose of 375 mg/m2. Subsequent doses of 1400 mg are administered subcutaneously on Day 1 of each cycle, for a further 7 cycles

Intervention Type: DRUG

rituximab [MabThera/Rituxan]

375 mg/m2 intravenously on Day 1 of each cycle, 8 cycles

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients, >/= 18 and </= 80 years of age at time of study inclusion
• Histologically confirmed, previously untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) according to the WHO classification system
• Patients with an International Prognostic Index (IPI) score 1-5, or IPI score 0 with bulky disease, defined as one lesion >/= 7.5 cm
• At least one bi-dimensionally measurable lesion defined as >/= 1.5 cm in its largest dimension on CT scan, PET-CT scan or MRI
• Adequate hematologic function
• Eastern Cooperative Oncology Group (EOCD) performance status </= 2

Exclusion Criteria

• Primary or secondary central nervous system lymphoma, histologic evidence of transformation to Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL, or primary DLBCL of the testis
• Transformed lymphoma or follicular lymphoma IIIB
• Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
• History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin, carcinoma in situ of the cervix, or a malignancy that has been treated without curative intent and has been in remission without treatment for >/= 5 years prior to enrolment
• Inadequate renal or hepatic function
• Known human immunodeficiency virus (HIV) infection or HIV seropositive status
• Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. Patients with occult or prior HBV infection as defined by protocol may be included. Patients positive for HCV antibody are eligible only if polymerase chain reaction testing for HCV ribonucleic acid is negative.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
• Prior treatment with cytotoxic drugs or rituximab for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody
• Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 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

EHS CAC Hospital FRANTZ FANON ZABANA BLIDA; Hematology ward

Blida, , Algeria

Centre hospitalo-univerisitaire de Tizi Ouzou - Nedir Mohamed;Service d'hématologie

Tizi Ouzou, , Algeria

Cemic; Haematology

Buenos Aires, , Argentina

Hospital Privado de Comunidad; Oncology

Mar del Plata, , Argentina

Onze Lieve Vrouwziekenhuis Aalst

Aalst, , Belgium

ZNA Middelheim

Antwerp, , Belgium

CHU Brugmann (Victor Horta)

Brussels, , Belgium

Clin Univ de Bxl Hôpital Erasme

Brussels, , Belgium

CHU Charleroi-ISPPC-Espace Santé

Charleroi, , Belgium

CHU de Charleroi

Charleroi, , Belgium

GHdC Site Notre Dame

Charleroi, , Belgium

UZ Gent

Ghent, , Belgium

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

AZ Turnhout Sint Elisabeth

Turnhout, , Belgium

CHR de Verviers - East Belgium

Verviers, , Belgium

Crio - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, Brazil

Instituto Nacional de Cancer - INCa; Oncologia

Rio de Janeiro, Rio de Janeiro, Brazil

Clinicas Oncologicas Integradas - COI

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital Giovanni Battista - Mae de Deus Center; Instituto do Cancer

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Amaral Carvalho

Jaú, São Paulo, Brazil

Hospital das Clinicas - FMUSP; Hematologia

São Paulo, São Paulo, Brazil

University Hospital Sv.Georgi Clnic of Hematology; Hematology

Plovdiv, , Bulgaria

Military Medical Academy; Hematology And Oncology

Sofia, , Bulgaria

UMHAT Alexandrovska EAD; Hematology

Sofia, , Bulgaria

Lion'S Gate Hospital

North Vancouver, British Columbia, Canada

Cancer Care Manitoba

Winnipeg, Manitoba, Canada

Regional health authority A vitalite health network

Moncton, New Brunswick, Canada

Royal Victoria Regional Health Centre; c/o Oncology Clinical Trials

Barrie, Ontario, Canada

William Osler Health System Brampton Civic Hospital

Brampton, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

Southlake Regional Health Center; Community Care Clinic / Oncology

Newmarket, Ontario, Canada

Toronto East General Hospital; Haematology/Oncology

Toronto, Ontario, Canada

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

Clínica Imbanaco; Oncology

Cali, , Colombia

Hospital Pablo Tobon Uribe

Medellin-Antioquia, , Colombia

Helsinki University Central Hospital; Dept of Oncology

Helsinki, , Finland

Middle Finland Central Hospital

Jyväskylä, , Finland

Oulu University Hospital; Oncology

Oulu, , Finland

Tampere University Hospital; Dept of Oncology

Tampere, , Finland

Turku Uni Central Hospital; Oncology Clinics

Turku, , Finland

Ch Victor Dupouy; Hematologie

Argenteuil, , France

Hopital Augustin Morvan; Hematologie

Brest, , France

Ch Du Mans; Medecine Hematologie Oncologie

Le Mans, , France

Centre ONCOGARD - Institut de Cancerologie du Gard

Nîmes, , France

Hopital Yves Le Foll; Hematologie Oncologie

Saint-Brieuc, , France

Ch De Saint Quentin; Medecine B10

Saint-Quentin, , France

Hopital Sud; Hematologie Clinique

Salouël, , France

Clinique Ste Anne

Strasbourg, , France

Hopital Hautepierre; Hematologie Oncologie

Strasbourg, , France

Hia Sainte Anne; Medecine Interne Oncologie

Toulon, , France

University General Hospital of Alexandroupolis; Haemotology

Alexandroupoli, , Greece

General Hospital of Athens Evangelismos; Hematology

Athens, , Greece

Laiko General Hospital; Hematology Clinic

Athens, , Greece

Metropolitan Hospital; Hematology Dept

Athens, , Greece

Periph. University General Hospital of Heraklion; Hematology

Heraklion, , Greece

University Hospital of Ioannina; Hematology

Ioannina, , Greece

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

Pátrai, , Greece

Theagenio Anticancer Hospital; Dept. of Haematology

Thessaloniki, , Greece

Georgios Papanikolaou Hospital; Hematology Department

Thessaloniki, , Greece

Cork Uni Hospital; Oncology Dept

Cork, , Ireland

Mater Misericordiae Uni Hospital; Oncology

Dublin, , Ireland

St James' Hospital; Cancer Clinical Trials Office

Dublin, , Ireland

Galway Uni Hospital; Oncology Dept

Galway, , Ireland

University Hospital Limerick - Oncology

Limerick, , Ireland

Haemek Medical Center; Hematology Department

Afula, , Israel

Rambam Medical Center; Heamatology & Bone Marrow Transplantation

Haifa, , Israel

Wolfson Mc; Haematology

Holon, , Israel

Shaare Zedek Medical Center; Hematology Dept.

Jerusalem, , Israel

Meir Medical Center; Heamatology Dept

Kfar Saba, , Israel

Beilinson Medical Center; Haematology

Petah Tikva, , Israel

Chaim Sheba Medical Center; Hematology BMT & CBB

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Ichilov Sourasky Medical Center; Heamatology

Tel Aviv, , Israel

Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia

Pescara, Abruzzo, Italy

Az. Osp. G. Moscati; U.O. Do Ematologia

Taranto, Apulia, Italy

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, Italy

Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia

Ravenna, Emilia-Romagna, Italy

Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia

Rimini, Emilia-Romagna, Italy

Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica

Aviano, Friuli Venezia Giulia, Italy

AOU Ospedali Riuniti; Ematologia

Trieste, Friuli Venezia Giulia, Italy

Uni Cattolica; Divisione Di Ematologia

Rome, Lazio, Italy

Az. Osp. Sant'Andrea; U.O. C. Ematologia

Rome, Lazio, Italy

ASST PAPA GIOVANNI XXIII; Ematologia

Bergamo, Lombardy, Italy

ASST DI CREMONA; U.O.S. di Ematologia

Cremona, Lombardy, Italy

Ospedale Di Circolo E Fondazione Macchi; Ematologia

Varese, Lombardy, Italy

Ospedale Mauriziano Umberto I

Turin, Piedmont, Italy

Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.

Cagliari, Sardinia, Italy

Azienda Ospedaliero Uni Ria Policlinico G. Martino; U.O. Di Oncologia Medica

Messina, Sicily, Italy

Casa Di Cura La Maddalena; Oncoematologia E Trapianto Del Midollo Osseo

Palermo, Sicily, Italy

Ospedale Civile; S.C. Ematologia

Pesaro, The Marches, Italy

A.O. Univ.Ospedali Riuniti Umerto I -G.M.Lancisi G.Salesi; U.O. Clinica Di Ematologia

Torrette Di Ancona, The Marches, Italy

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

Perugia, Umbria, Italy

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

Padua, Veneto, Italy

Medisch Centrum Alkmaar

Alkmaar, , Netherlands

Meander Medisch Centrum; Locatie Lichtenberg

Amersfoort, , Netherlands

Deventer Ziekenhuis; Interne Geneeskunde

Deventer, , Netherlands

Albert Schweitzer Ziekenhuis

Dordrecht, , Netherlands

Maxima Medisch Centrum; Inwendige Geneeskunde

Eindhoven, , Netherlands

Groene Hart Ziekenhuis Bleulandlocatie; Inwendige Geneeskunde

Gouda, , Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Atrium Medisch Centrum

Heerlen, , Netherlands

Spaarne Ziekenhuis; Inwendige Geneeskunde

Hoofddorp, , Netherlands

Medisch Centrum Leeuwarden; Interne

Leeuwarden, , Netherlands

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, , Netherlands

Erasmus Mc - Locatie Centrum; Dept of Hematology

Rotterdam, , Netherlands

Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed

Rotterdam, , Netherlands

Maasstad ziekenhuis

Rotterdam, , Netherlands

Zuyderland ziekenhuis locatie Geleen

Sittard-Geleen, , Netherlands

Isala Klinieken, Locatie Sophia; Inwendige Geneeskunde

Zwolle, , Netherlands

Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica

Chiclayo, , Peru

Instituto;Oncologico Miraflores

Lima, , Peru

Oncosalud Sac; Oncología

Lima, , Peru

Katedra i Klinika Hematologii i Transplantacji Szpiku SUM

Katowice, , Poland

Swietokrzyskie Centrum Onkologii; Onkologia Ogolna

Kielce, , Poland

Malopolskie Centrum Medyczne

Krakow, , Poland

Szpital Wojewodzki w Opolu, Oddzial Hematologii i Onkologii Hematologicznej

Opole, , Poland

Wojewodzki Szpital Specjalistyczny im. J. Korczaka; Oddział Chorób Wewnetrznych/Hematologiczny

Słupsk, , Poland

Centrum Onkologii Instytut im. M. Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego

Warsaw, , Poland

HUC; Servico de Hematologia

Coimbra, , Portugal

Hospital Santo Antonio dos Capuchos; Servico de Hemato-Oncologia

Lisbon, , Portugal

Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula

Lisbon, , Portugal

IPO do Porto; Servico de Onco-Hematologia

Porto, , Portugal

Hospital de Sao Joao; Servico de Hematologia Clinica

Porto, , Portugal

Regional Oncology Center

Chelyabinsk, , Russia

Republican Clinical Oncologic Dispensary of Republic Of Tatarstan

Kazan', , Russia

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

Moscow, , Russia

Rus Med Academy for Postgraduate Education; Oncology Department

Moscow, , Russia

Vladimirskiy Regional Scientific Research Inst. ; Hematology

Moscow, , Russia

Regional Clinical Hospital N.A. Semashko; Hematology

Nizhny Novgorod, , Russia

Clinical MSCh No1

Perm, , Russia

Saint-Petersburg SHI City Clinical Hospital #31

Saint Petersburg, , Russia

City Clinical Hospital #15; Hematology department

Saint Petersburg, , Russia

Central City Hospital #7; Hematology

Yekaterinburg, , Russia

Riyadh Military Hospital

Riyadh, , Saudi Arabia

Clinical Center Kragujevac;Center for Hematology

Kragujevac, , Serbia

Clinic of Haematology Cc Nis

Niš, , Serbia

National Hospital; Oncotherapy Dept

Bloemfontein, , South Africa

Tygerberg Hospital; Haematology Department

Cape Town, , South Africa

Steve Biko Academic Hospital; Oncology

Pretoria, , South Africa

Corporacio Sanitaria Parc Tauli; Servicio de Hematologia

Sabadell, Barcelona, Spain

Hospital Punta Europa; Servicio de Hematologia

Algeciras, Cadiz, Spain

Hospital Universitario Marques de Valdecilla; Servicio de Hematologia

Santander, Cantabria, Spain

Hospital de Donostia; Servicio de Hematologia

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital de Gran Canaria Dr. Negrin; Servicio de Oncologia

Las Palmas de Gran Canaria, Las Palmas, Spain

Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Hematologia

Las Palmas de Gran Canarias, Las Palmas, Spain

Hospital de Cabueñes; Servicio de Hematología y Hemoterapia

Gijón, Principality of Asturias, Spain

Hospital de Cruces; Servicio de Hematologia

Barakaldo, Vizcaya, Spain

Hospital General Univ. de Alicante; Servicio de Oncologia

Alicante, , Spain

Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Hematologia

Girona, , Spain

Hospital Lucus Augusti; Servicio de Hematologia

Lugo, , Spain

Hospital General Universitario Gregorio Marañon; Servicio de Hematología

Madrid, , Spain

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, , Spain

Hospital Universitario la Paz; Servicio de Hematologia

Madrid, , Spain

Hospital Universitario Puerta de Hierro; Servicio de Oncologia

Madrid, , Spain

Hospital Costa del Sol; Servicio de Hematologia

Málaga, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Hospital Universitario Dr. Peset; Servicio de Hematologia

Valencia, , Spain

Hospital Clinico Universitario Lozano Blesa; Servicio de Hematologia

Zaragoza, , Spain

Hospital Universitario Miguel Servet; Servicio Hematologia

Zaragoza, , Spain

King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine

Bangkok, , Thailand

Ramathibodi Hospital; Division of Hematology, Department of Medicine

Bangkok, , Thailand

Siriraj Hospital; Division of Hematology, Department of Medicine

Bangkok, , Thailand

Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine

Khon Kaen, , Thailand

Cukurova Uni ; Hematology

Adana, , Turkey (Türkiye)

Diskapi Research And Training Hospital; hematology

Ankara, , Turkey (Türkiye)

Hacettepe Uni Medical Faculty; Hematology

Ankara, , Turkey (Türkiye)

Ankara University; Hematology

Ankara, , Turkey (Türkiye)

Gaziantep Uni Medical School; Hematology

Gaziantep, , Turkey (Türkiye)

Istanbul University Cerrahpasa Medical Faculty; Hematology Department

Istanbul, , Turkey (Türkiye)

Dokuz Eylul Uni ; Hematology

Izmir, , Turkey (Türkiye)

Ege Uni Medical School; Hematology

Izmir, , Turkey (Türkiye)

Erciyes Uni ; Hematology

Kayseri, , Turkey (Türkiye)

Ondokuzmayis University Medical Faculty Heamatology Department

Samsun, , Turkey (Türkiye)

Cumhuriyet Uni. Med. Fac.; Hematology

Sivas, , Turkey (Türkiye)

Karadeniz Technical Uni School of Medicine; Hematology

Trabzon, , Turkey (Türkiye)

Mun. Multifield Clin.Hosp.#4,Dept. of Chemotherapy, DSMU; Chair of Oncology and Medical Radiology

Dnipropetrovsk, , Ukraine

Kyiv City Clinical Oncological Center; Chemotherapy Department

Kiev, , Ukraine

State Oncology Regional Treatment-Diagnostic Center; Chemotherapy Department

Lviv, , Ukraine

SOUTHMEAD HOSPITAL; Richard Bright Dialysis Centre

Bristol, , United Kingdom

Ipswich Hospital; Oncology Pharmacy

Ipswich, , United Kingdom

Macclesfield District General Hospital

Macclesfield, , United Kingdom

Kings Mill Hospital

Sutton in Ashfield, , United Kingdom

Singleton Hospital: Pharmacy Department

Swansea, , United Kingdom

Instituto de Oncologia y Hematologia UCV

Caracas, , Venezuela

Banco Municipal de Sangre; Hematología

Caracas, , Venezuela

Countries

India; Algeria; Argentina; Belgium; Brazil; Bulgaria; Canada; Colombia; Finland; France; Greece; Ireland; Israel; Italy; Netherlands; Peru; Poland; Portugal; Russia; Saudi Arabia; Serbia; South Africa; Spain; Thailand; Turkey (Türkiye); Ukraine; United Kingdom; Venezuela

References

Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. doi: 10.3324/haematol.2017.173583. Epub 2017 Sep 21.

Reference Type: DERIVED

PMID: 28935843 (View on PubMed)

Other Identifiers

2012-000669-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO28107

Identifier Type: -

Identifier Source: org_study_id