A Study of Bevacizumab (Avastin) in Combination With Rituximab (MabThera) and CHOP (Cyclophosphamide, Hydroxydaunorubicin [Doxorubicin], Oncovin [Vincristine], Prednisone) Chemotherapy in Patients With Diffuse Large B-cell Lymphoma

June 26, 2017 updated by: Hoffmann-La Roche

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Trial Comparing the Efficacy of Bevacizumab in Combination With Rituximab and CHOP (R-CHOP + Bevacizumab) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients With CD20-positive Diffuse Large B-cell Lymphoma (DLBCL)

This 2-arm study was designed to compare the efficacy and safety of bevacizumab (Avastin) in combination with rituximab (MabThera) and CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) chemotherapy (R-CHOP) versus rituximab plus CHOP chemotherapy (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL). Patients were randomized to receive 8 cycles of treatment with R-CHOP plus bevacizumab or R-CHOP plus placebo. Treatment with bevacizumab/placebo and R-CHOP was given either on a 2-week or 3-week schedule and bevacizumab was given at a weekly average dose of 5 mg/kg (10 mg/kg for 2-week cycles and 15 mg/kg for 3-week cycles).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

An independent Data and Safety Monitoring Board (DSMB) was established to review safety data collected during the study on an ongoing basis. At its meeting in December 2009, the DSMB noted a trend for increased cardiac toxicity in the experimental arm (R-CHOP + bevacizumab) compared with the control arm (R-CHOP + placebo). Additional efficacy analyses of data from 720 randomized patients were presented at a DSMB meeting on May 22, 2010; they indicated no improvement in efficacy with the addition of bevacizumab to R-CHOP. It was noted, however, that there was an apparent increase in the risk of cardiotoxicity, premature treatment withdrawal, serious adverse events (SAEs), fatal adverse events (AEs), and perforation/ulcer in the experimental arm. Based on its assessment of an increased risk with unlikely benefit for patients randomized to the experimental arm, the DSMB recommended that further enrollment in the study be permanently halted and that bevacizumab be discontinued for any patients randomized to the experimental arm. On May 31, 2010, the sponsor took the decision to stop enrollment into the study and the bevacizumab treatment was terminated with immediate effect as recommended by the DSMB.

The study protocol was amended. The primary objective of the study was changed from evaluation of efficacy to evaluation of safety and the study was extended to include an 18-month safety follow-up period. Because enrollment was terminated prematurely resulting in fewer enrolled patients than planned, the outcome measure data are premature due to fewer than expected events.

The time frame for the reporting of serious adverse events was modified. Serious adverse events (SAE) unrelated to study treatment were reported until 1 year post-treatment or until new anti-lymphoma treatment was initiated. SAEs judged to be related to study treatment and congestive heart failure events were reported at any time during the study.

Study Type

Interventional

Enrollment (Actual)

787

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1114AAN
        • Fundaleu; Haematology
      • Buenos Aires, Argentina, C1280AEB
        • Hospital Britanico; Haematology
      • Buenos Aires, Argentina, 1425
        • Hospital Italiano; Haemathology
      • Córdoba, Argentina, 5016
        • HOSPITAL PRIVADO - CENTRO MEDICO DE CÓRDOBA; Dpto Oncología
  • Australia
    • Queensland
      • Greenslopes, Queensland, Australia, 4120
        • Greenslopes Private Hospital; Gallipoli Research Centre
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital; Haematology, Institute of Medical Veterinary Science
      • Kurralta Park, South Australia, Australia, 5037
        • Ashford Cancer Center Research
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Frankston Hospital; Oncology/Haematology
      • Melbourne, Victoria, Australia, 3000
        • Peter Maccallum Cancer Institute; Medical Oncology
      • Melbourne, Victoria, Australia, 3181
        • Alfred Hospital; Bone Marrow Transplant Unit
      • Wodonga, Victoria, Australia, 3690
        • Border Medical Oncology; Murray Valley Private Hospital
    • Western Australia
      • Fremantle, Western Australia, Australia, 6160
        • Fremantle Hospital; Haematology
  • Austria
      • Graz, Austria, 8036
        • Lkh-Univ. Klinikum Graz; Klinik Für Innere Medizin I
      • Salzburg, Austria, 5020
        • Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
      • Wien, Austria, 1090
        • Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Hämatologie & Hämostaseologie
  • Brazil
    • GO
      • Goiania, GO, Brazil, 74140-050
        • Centro Goiano de Oncologia - CGO
    • RS
      • Ijui, RS, Brazil, 98700-000
        • Hospital de Caridade de Ijui; Oncologia
      • Porto Alegre, RS, Brazil, 91350-200
        • Hospital Nossa Senhora da Conceição
      • Porto Alegre, RS, Brazil, 90035-903
        • Hospital das Clinicas - UFRGS; Hematologia
    • SP
      • Campinas, SP, Brazil, 13083-888
        • Hospital das Clinicas - UNICAMP
      • Santo Andre, SP, Brazil, 09060-650
        • Faculdade de Medicina do ABC - FMABC; Oncologia e Hematologia
      • Sao Paulo, SP, Brazil, 05403-000
        • Hospital das Clinicas - FMUSP; Hematologia
      • Sao Paulo, SP, Brazil, 01221-020
        • Santa Casa de Misericordia de Sao Paulo; Hematologia e Hemoterapia
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre; Dept of Medicine
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute ; Dept of Medical Oncology
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • Cancer Care Manitoba
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Moncton Hospital
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Health Science Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • QEII HSC; Oncology
    • Ontario
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario; Kingston General Hospital
      • Mississauga, Ontario, Canada, L5M 2N1
        • Credit Valley Hospital/Carlo Fidani Peel Regional Cancer Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Toronto Sunnybrook Regional Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
      • Windsor, Ontario, Canada, N8W 2X3
        • Windsor Regional Cancer Centre
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
      • Montreal, Quebec, Canada, H3A 1A1
        • Mcgill University - Royal Victoria Hospital; Oncology
      • Montreal, Quebec, Canada, H3T 1E2
        • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
      • Quebec City, Quebec, Canada, G1J 1Z4
        • Hopital de L'Enfant-Jesus; Hematology
      • Quebec City, Quebec, Canada, G1R 2J6
        • Chuq - Hopital Hotel Dieu de Quebec; Oncology
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre; Uni of Saskatoon Campus
  • China
      • Beijing, China, 100021
        • Cancer Hospital Chinese Academy of Medical Sciences.
      • Beijing, China, 100142
        • Beijing Cancer Hospital
      • Beijing, China, 100730
        • Beijing Union Hospital
      • Beijing, China, 100853
        • General Hospital of Chinese PLA; Department of Hematology
      • Fuzhou, China, 350014
        • Fujian Cancer Hospital
      • Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center
      • Shanghai, China, 200433
        • Changhai Hospital of Shanghai
      • Shanghai, China, 200127
        • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Suzhou, China, 215006
        • First Affiliated Hospital of Soochow University
      • Suzhou, China, 215004
        • The Second Affiliated Hospital of Soochow University
      • Tianjin, China, 300020
        • Tianjin Institute of Hematology & Blood Diseases Hospital
      • Xi'an, China, 710032
        • The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
  • Colombia
      • Bogota, Colombia
        • Organizacion Sanitas Internacional
      • Medellin, Colombia, 2A-80
        • Instituto Cancerologia Medellin; Clinica Las Americas
      • Medellin-Antioquia, Colombia
        • Hospital Pablo Tobón Uribe
      • Pereira, Colombia, 600004
        • Oncólogos de Occidente
  • Czechia
      • Brno, Czechia, 625 00
        • Fakultni nemocnice Brno; Interni hematoonkologicka klinika
      • Hradec Kralove, Czechia, 500 05
        • Fn Hr. Kralove; IV. Interni Hematologicka Klinika
      • Olomouc, Czechia, 775 20
        • Fakultni nemocnice Olomouc; Hemato-onkologicka klinika
      • Plzen - Lochotin, Czechia, 304 60
        • Fakultni Nemocnice Plzen, Hematologicko-Onkologicke Oddeleni
      • Praha, Czechia, 100 34
        • Fakultní Nemocnice Královské Vinohrady; Hematologická Klinika
      • Praha 2, Czechia, 128 08
        • VshEOBECNÁ FAKULTNÍ NEMOCNICE; I. INTERNI KLINIKA
  • Ecuador
      • Guayaquil, Ecuador, EC090150
        • Teodoro Maldonado Carbo Hospital; Oncology Service
      • Quito, Ecuador, 2569
        • Hospital Carlos Andrade Marin; Servicio de Oncología
      • Quito, Ecuador, EC170124
        • Hospital Solca Quito; Oncologia
  • France
      • Albi, France, 81030
        • Clinique Claude Bernard; Onco Hematologie
      • Angers, France, 49033
        • Centre Hospitalier Uni Ire; Service de Medecine D
      • Bordeaux, France, 33077
        • Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie
      • Bordeaux, France, 33076
        • Institut Bergonie; Hematologie Oncologie
      • Caen, France, 14076
        • Centre Francois Baclesse; Comite 2
      • Clermont Ferrand, France, 63003
        • Chu Estaing; Cons Hemato Medecine Interne
      • Dijon, France, 21079
        • Chu Site Du Bocage;Hematologie Clinique
      • La Roche Sur Yon, France, 85925
        • CH Dptal Les Oudairies; Hematologie Oncologie
      • La Tronche, France, 38700
        • Hopital Albert Michallon; Oncologie
      • Le Mans, France, 72015
        • Clinique Victor Hugo; Chimiotherapie
      • Lille, France, 59037
        • Hopital Claude Huriez; Hematologie
      • Limoges, France, 87042
        • Hopital Uni Ire Dupuytren; Hematologie
      • Lyon, France, 69373
        • Centre Leon Berard; Departement Oncologie Medicale
      • Marseille, France, 13273
        • Institut J Paolii Calmettes; Onco Hematologie 1
      • Montauban, France, 82017
        • Clinique Pont de Chaume; Oncologie Et Radiotherapie
      • Montpellier, France, 34295
        • Hopital Saint Eloi; Hematologie Oncologie Medicale
      • Nice, France, 06202
        • Hopital de L'Archet; Hematologie Clinique
      • Nimes, France, 30900
        • Polyclinique Kenval ; Radiotherapie Oncologie
      • Paris, France, 75231
        • Institut Curie; Oncologie Medicale
      • Paris, France, 75475
        • Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
      • Paris, France, 75651
        • Hopital Pitie Salpetriere; Hematologie Clinique
      • Perpignan, France, 66046
        • Hopital Saint Jean; Hematologie
      • Pessac, France, 33604
        • Hopital De Haut Leveque; Hematologie Clinique
      • Pierre Benite, France, 69495
        • Ch Lyon Sud; Hemato Secteur Jules Courmont
      • Poitiers, France, 86021
        • Hopital De La Miletrie; Hematologie Et Oncologie Medicale
      • Rodez, France, 12027
        • Ch Jacques Puel;Oncologie Medicale
      • Saint-Priest en Jarez, France, 42271
        • ICL; Hematologie
      • Salouel, France, 80480
        • Hopital Sud; Hematologie Clinique
      • Toulouse, France, 31076
        • Clinique Pasteur; Oncologie Medicale
      • Toulouse, France, 31059
        • Hopital Purpan; Hematologie Clinique
      • Tours, France, 37044
        • Hopital Bretonneau; Hematologie Therapie Cellulaire
      • Vandoeuvre Les Nancy, France, 54511
        • Hopitaux De Brabois; Hematologie Medecine Interne
      • Villejuif, France, 94805
        • Institut Gustave Roussy; Unite D'Hematologie
  • Germany
      • Amberg, Germany, 92224
        • Gesundheitszentrum St. Marien GmbH; Med. II, Hämatologie/Onkologie
      • Berlin, Germany, 10117
        • Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.
      • Berlin, Germany, 10117
        • Charité; Onkologie & Hämatologie
      • Bremen, Germany, 28239
        • DIAKO Ev. Diakonie-Krankenhaus Bremen GmbH; Med. Klinik II; Hämatologie und internistische Onkologie
      • Cottbus, Germany, 03048
        • Carl-Thiem-Klinik Cottbus; Medizinische Klinik
      • Dortmund, Germany, 44137
        • Klinikzentrum Mitte; Medizinische Klinik Gastroenterologie Haematologie / Onkologie
      • Dortmund, Germany, 44137
        • St. Johannes Hospital; Abt. Innere Medizin
      • Eschweiler, Germany, 52249
        • St Antonius Hospital; Haematologie/Onkologie
      • Frankfurt, Germany, 60488
        • Krankenhaus Nordwest Medizinische Klinik
      • Fulda, Germany, 36043
        • Klinik Fulda; Abt. Itz
      • Greifswald, Germany, 17475
        • Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
      • Göttingen, Germany, 37075
        • Georg-August-Uniklinik ; Zentrum Innere Medizin Abt. Hämatologie & Onkologie
      • Hagen, Germany, 58095
        • Kath.Krankenhaus Hagen gem.GmbH St.-Marien-Hospital
      • Hamburg, Germany, 20249
        • Facharztzentrum Eppendorf, Studien GbR
      • Hamburg, Germany, 20099
        • Asklepios Klinik St. Georg; Allgemeine Innere Medizin
      • Hamm, Germany, 59063
        • Evang.Krankenhaus Abt. Hämatologie und Onkologie
      • Hamm, Germany, 59071
        • St.-Marien-Hospital Klinik Knappenstraße; Klinik für Hämatologie und Onkologie
      • Hannover, Germany, 30449
        • KRH Klinikum Siloah Medizinische Klinik III
      • Hildesheim, Germany, 31134
        • St. Bernward-Krankenhaus
      • Homburg/Saar, Germany, 66421
        • Universitaetsklinikum des Saarlandes; medizinische Klinik und Poliklinik; Innere Medizin I
      • Karlsruhe, Germany, 76137
        • St. Vincentius Kliniken Ag; Medizinische Klinik Abt. 2
      • Karlsruhe, Germany, 76133
        • Städtisches Klinikum Karlsruhe gGmbH, II. Medizinische Klinik
      • Landshut, Germany, 84028
        • Tagesklinik Landshut; Hämatologie/Onkologie
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog.
      • Leipzig, Germany, 04129
        • Klinikum St.Georg gGmbH Klinik für Internistische Onkologie und Hämotologie
      • Ludwigshafen, Germany, 67063
        • Klinikum der Stadt Ludwigshafen; Medizinische Klinik A
      • Lübeck, Germany, 23562
        • Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie
      • Lüdenscheid, Germany, 58515
        • Märkische Kliniken GmbH, Klinikum Lüdenscheid; Hämatologie / Onkologie
      • Magdeburg, Germany, 39120
        • Otto von Guericke Uni Magdeburg Uniklinik; Hämatologie/Onkologie
      • Magdeburg, Germany, 39130
        • Klinikum Magdeburg gemeinnützige GmbH; Klinik Haematologie und Onkologie
      • Mannheim, Germany, 68167
        • Klinikum Mannheim III. Medizinische Klinik
      • Muenchen, Germany, 81377
        • Klinikum der Universitaet Muenchen; Campus Großhadern; Medizinische Klinik III und Poliklinik
      • Münster, Germany, 48149
        • Westfälische Wilhelms-Universität Münster, Medizinische Klinik und Poliklinik A
      • Oldenburg, Germany, 26133
        • Klinikum Oldenburg gGmbH; Klinik für Onkologie und Hämatologie
      • Recklinghausen, Germany, 45659
        • Prosper-Hospital, Medizinische Klinik I
      • Siegen, Germany, 57072
        • St Marien Krankenhaus; Medizinische Klinik Iii
      • Trier, Germany, 54290
        • Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
      • Trier, Germany, 54292
        • Krankenhaus der Barmherzigen Brüder Trier; Innere Medizin I, Hämatologie / Internistische Onkologie
      • Tübingen, Germany, 72076
        • Eberhard-Karls-Universität Tübingen; Medizinische Klinik I
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
      • Wiesbaden, Germany, 65199
        • HSK Dr.-Horst-Schmidt-Kliniken; Innere Medizin I Kardiologie; Angiologie und Intensivmedizin
      • Wuppertal, Germany, 42283
        • Helios Klinik Wuppertal; Medizinische Klinik I
      • Wuppertal, Germany, 42283
        • Kliniken St. Antonius; Zentrum Für Innere Medizin, Haematologie/Onkologie
  • Greece
      • Thessaloniki, Greece, 570 10
        • Georgios Papanikolaou Hospital; Hematology Department
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital; Dept of Medicine
      • Hong Kong, Hong Kong
        • Queen Elizabeth Hospital; Clinical Oncology
  • Hungary
      • Budapest, Hungary, 1122
        • National Institute of Oncology, A Dept of Internal Medicine
      • Budapest, Hungary, 1097
        • Fov. Onk. Egyesitett Szent Istvan es Szent Laszlo Korhaz; Dept Of Bone Marrow Transplant
      • Debrecen, Hungary, 4032
        • University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology
  • Italy
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
      • Parma, Emilia-Romagna, Italy, 43100
        • Ospedale Regionale Di Parma; Divisione Di Oncologia Medica
      • Reggio Emilia, Emilia-Romagna, Italy, 42100
        • Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia
    • Friuli-Venezia Giulia
      • Aviano, Friuli-Venezia Giulia, Italy, 33081
        • Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
      • Udine, Friuli-Venezia Giulia, Italy, 33100
        • A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica
    • Lazio
      • Roma, Lazio, Italy, 00161
        • Univ. Cattolica La Sapienza; Cattedra Di Ematologia
    • Lombardia
      • Monza, Lombardia, Italy, 20052
        • ASST DI MONZA; Ematologia
      • Pavia, Lombardia, Italy, 27100
        • Irccs Policlinico San Matteo; Divisione Di Ematologia
    • Marche
      • Ascoli Piceno, Marche, Italy, 63100
        • Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia
    • Molise
      • Campobasso, Molise, Italy, 86100
        • Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia
    • Piemonte
      • Orbassano, Piemonte, Italy, 10043
        • Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico
      • Torino, Piemonte, Italy, 10126
        • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
    • Puglia
      • Bari, Puglia, Italy, 70124
        • Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
    • Sicilia
      • Via S. Sofia 78, Sicilia, Italy, 95123
        • Ospedale Ferrarotto; Divisione Di Ematologia
    • Toscana
      • Pisa, Toscana, Italy, 56100
        • Ospedale Santa Chiara; Unita Operativa Di Ematologia
  • Korea, Republic of
      • Seoul, Korea, Republic of, 135-170
        • Samsung Medical Centre; Oncology
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology
      • Seoul, Korea, Republic of, 139-709
        • Korean Cancer Center Hospital; Oncology
      • Seoul, Korea, Republic of
        • Severance Hospital - Yonsei University; Medicine Dept.
  • Lithuania
      • Klaipeda, Lithuania, 92288
        • Seamen' Hospital' Dept. of haematology
      • Vilnius, Lithuania, 08661
        • Uni Hospital Santariskiu Clinic; Haematology
  • Malaysia
      • Penang, Malaysia, 10990
        • Hospital Pulau Pinang
  • Mexico
      • Aguascalientes, Mexico, 20127
        • Instituto Biomedico De Investigacion A.C.
      • Mexico City, Mexico, 11520
        • Hospital Español; Hematología Sala 19
      • Monterrey, Mexico, 64460
        • Hospital Universitario Dr. Jose E. Gonzalez; Haematology
      • Monterrey, Mexico, 00000
        • Col Instituto Tecnologico Y Estudios Superiores de Monterrey
  • New Zealand
      • Auckland, New Zealand, 1309
        • North Shore Hospital; Haematolgy
      • Auckland, New Zealand
        • Uni of Auckland; Dept of Molecular Medicine & Haematology
      • Christchurch, New Zealand
        • Christchurch Hospital; Canterbury Health Laboratories
  • Panama
      • Panama City, Panama, 083200752
        • Centro Hemato Oncologico Paitilla
  • Peru
      • Chiclayo, Peru, CIX
        • Hospital Nacional Almanzor Aguinaga Asenjo; Unidad De Investigacion Del Servicio De Oncologia Medica
      • Lima, Peru, 34
        • Instituto Nacional de Enfermedades Neoplasicas
      • Lima, Peru, 13
        • Hospital Nacional Guillermo Almenara Irigoyen; Oncology
      • Lima, Peru, 11
        • Hospital Nacional Edgardo Rebagliati Martins; Oncologia
      • Lima, Peru, Lima11
        • Hospital Nacional LNS dela Policia Nacional del Perú. Unidad Onco; Deapartamento de Oncología
  • Philippines
      • Cebu, Philippines, 6000
        • Cebu Cancer Institute; Perpetual Succour Hospital
      • Diliman, Quezon City, Philippines, 1100
        • National Kidney and Transplant Institute; Chemotherapy Unit
      • Quezon City, Philippines, 1114
        • St Luke'S Medical Centre; Oncology
  • Poland
      • Brzozów, Poland, 36-200
        • Szpital Specjalistyczny Podkarpacki Ośrodek Onkologiczny
      • Krakow, Poland, 31-501
        • Szpital Uniwersytecki W Krakowie; Klinika Hematologii
      • Lodz, Poland, 93-510
        • Medical University School; Dept. of Haematology
      • Lublin, Poland, 20-081
        • Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
      • Olsztyn, Poland, 10-228
        • Zaklad Opieki Zdrowotnej Mswia; Oddzial Chemioterapii
      • Warszawa, Poland, 02-781
        • Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Lymphoma Dept.
      • Warszawa, Poland, 02-097
        • Samodzielny Publiczny Centralny Szpital Kliniczny; Haematology Dept.
      • Warszawa, Poland, 02-507
        • Centralny Szpital Kliniczny Mswia; Klinika onkologii, hematologii i chorob wewnetrznych
  • Portugal
      • Coimbra, Portugal, 3000-075
        • HUC; Servico de Hematologia
      • Lisboa, Portugal, 1099-166
        • IPO de Lisboa; Servico de Hematologia
      • Porto, Portugal, 4200-319
        • Hospital de Sao Joao; Servico de Hematologia Clinica
  • Russian Federation
      • Kazan, Russian Federation, 420029
        • Republican Clinical Oncologic Dispensary of Republic Of Tatarstan
      • Moscow, Russian Federation, 115478
        • N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
      • Moscow, Russian Federation, 125167
        • Haematology Research Center; Haematology
      • Moscow, Russian Federation, 129128
        • Semashko Central Clinical Hospital Moscow; Hematology
      • St Petersburg, Russian Federation, 191024
        • Research Inst. of Hematology & Blood Transfusion ; Hematology
  • Slovakia
      • Bratislava, Slovakia, 833 10
        • National Cancer Inst. ; Dept. of Chemotherapy
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron; Servicio de Hematologia
      • Barcelona, Spain, 08036
        • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
      • Barcelona, Spain, 08907
        • Hospital Duran i Reynals; Servicio de Hematologia
      • Jaen, Spain, 23007
        • Complejo Hospitalario de Jaen- Hospital Universitario Medico Quirurgico; Servicio de Hematologia
      • Madrid, Spain, 28046
        • Hospital Universitario la Paz; Servicio de Hematologia
      • Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos; Servicio de Hematología
      • Malaga, Spain, 29010
        • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
      • Salamanca, Spain, 37007
        • Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio; Servicio de Hematologia
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
      • Valencia, Spain, 46009
        • Hospital Universitario la Fe; Servicio de Medicina Intena
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet; Servicio Hematologia
    • Barcelona
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Mutua de Terrassa; Servicio de Hematologia
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
    • La Coruña
      • La Coruna, La Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia
    • Tenerife
      • La Laguna, Tenerife, Spain, 38320
        • Hospital Universitario de Canarias;servicio de Oncologia
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
        • Hospital de Basurto; Servicio de Hematologia
      • Galdakano, Vizcaya, Spain, 48960
        • Hospital de Galdakano
  • Sweden
      • Lund, Sweden, 22185
        • Skånes University Hospital, Skånes Department of Onclology
      • Malmö, Sweden, 205 02
        • Skånes Universitetssjukhus; Kliniska Forskningsenheten Onkologimottagning medicinsk behandling
      • Sundsvall, Sweden, 85186
        • Länssjukhuset; Medicinkliniken
      • Uppsala, Sweden, 75185
        • Akademiska sjukhuset, Onkologkliniken
  • Switzerland
      • Zürich, Switzerland, 8091
        • Universitätsspital Zürich; Klinik für Onkologie
  • Taiwan
      • Taipei, Taiwan, 00112
        • Veterans General Hospital; Division of Oncology
      • Taipei, Taiwan, 112
        • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
      • Taoyuan, Taiwan, 333
        • Chang Gung Medical Foundation-Taipei
  • Thailand
      • Bangkok, Thailand, 10400
        • National Cancer Inst.
      • Bangkok, Thailand, 10330
        • King Chulalongkorn Memorial Hospital; Division of Hematology, Department of Medicine
      • Bangkok, Thailand, 10400
        • Rajavithi Hospital; Medicine
      • Bangkok, Thailand, 10700
        • Siriraj Hospital; Division of Hematology, Department of Medicine
      • Chiang Mai, Thailand, 50200
        • Chiang Mai Uni Hospital; Division of Hematology,Dept of Medicine,Faculty of Medicine
      • Khon Kaen, Thailand, 40002
        • Srinagarind Hospital, Khon Kaen Uni ; Dept of Medicine
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital; Department of Haematology
      • Bradford, United Kingdom, BD9 6RJ
        • Bradford Royal Infirmary; Haematology Department
      • Hampshire, United Kingdom, RG24 9NA
        • North Hampshire Hospital; Dept. of Haematology
      • Harlow, United Kingdom, CM20 1QX
        • Princess Alexandra Hospital; Department of Haematology
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary; Dept. of Medical Oncology
      • Liverpool, United Kingdom, L7 8XP
        • Royal Liverpool Uni Hospital; Haematology
      • London, United Kingdom, SW17 0QT
        • St. George'S Hospital; Haematology
      • Middx, United Kingdom, UB8 3NN
        • Hillingdon Hospital
      • Oxford, United Kingdom, OX3 7LJ
        • Churchill Hospital; Oxford Cancer and Haematology Centre
      • Sheffield, United Kingdom, S10 2SJ
        • Weston Park Hospital; Cancer Clinical Trials Centre
      • Sheffield, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital; Haematology Dept
      • Wolverhampton, United Kingdom, WV10 0QP
        • The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Uni of California - San Diego; Cancer Center & Dept of Medicine
      • Whittier, California, United States, 90603
        • Kenmar Research Inst.
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center Department of Hematology
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Uni Medical Center; Division Of Hemotology/Oncology
      • West Palm Beach, Florida, United States, 33401
        • Florida Cancer Specialists
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Centers
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center; Department of Hematology
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • St. Joseph Mercy Hospital; Department of Oncology
    • North Carolina
      • Concord, North Carolina, United States, 28025
        • NorthEast Oncology Associates
      • Winston-Salem, North Carolina, United States, 27103
        • Forsyth Regional Cancer Center; Piedmont Hematology/Oncology Associates
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • South Carolina
      • Charleston, South Carolina, United States, 29406
        • Charleston Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390-9063
        • Uni of Texas Southwestern Medical Center
      • San Antonio, Texas, United States, 78229
        • Cancer Therapy & Research Center
    • Washington
      • Federal Way, Washington, United States, 98003
        • Northwest Medical Specialties B
      • Puyallup, Washington, United States, 98372
        • Rainier Physicians
      • Tacoma, Washington, United States, 98405
        • Northwest Medical Specialties

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients, ≥ 18 and < 80 years of age.
  • CD20-positive diffuse large B-cell lymphoma.
  • Low-intermediate, high-intermediate, or high risk disease and/or bulky tumor (largest diameter ≥ 7.5 cm).
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

  • Prior treatment for diffuse large B-cell lymphoma.
  • Types of non-Hodgkin's lymphoma other than diffuse large B-cell lymphoma (DLBCL).
  • Central nervous system (CNS) involvement of lymphoma.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bevacizumab + rituximab + CHOP
Patients received bevacizumab 5 mg/kg/week on Day 1 of each cycle + rituximab 375 mg/m^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone).
Drug: Bevacizumab
Bevacizumab was administered at a dose of 15 mg/kg IV on Day 1 of each 21-day cycle for 8 cycles or at a dose 10 mg/kg IV on Day 1 of each 14-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Other Names:
  • Avastin
Drug: Rituximab
Rituximab was administered at a dose of 375 mg/m^2 IV on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Other Names:
  • MabThera
Drug: CHOP
Cyclophosphamide was administered at a dose of 750 mg/m^2 IV on Day 1 of each cycle. Doxorubicin was administered at a dose of 50 mg/m^2 IV on Day 1 of each cycle. Vincristine was administered at a dose of 1.4 mg/m^2 IV (maximum of 2 mg) on Day 1 of each cycle. Prednisone was administered at a dose of 100 mg orally on Days 1-5 of each cycle. All 4 drugs were administered either every 21 days for 8 cycles or every 14 days for 6 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Active Comparator: Placebo + rituximab + CHOP
Patients received placebo to bevacizumab on Day 1 of each cycle + rituximab 375 mg/m^2 intravenously (IV) on Day 1 of each cycle + CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone).
Drug: Rituximab
Rituximab was administered at a dose of 375 mg/m^2 IV on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Other Names:
  • MabThera
Drug: CHOP
Cyclophosphamide was administered at a dose of 750 mg/m^2 IV on Day 1 of each cycle. Doxorubicin was administered at a dose of 50 mg/m^2 IV on Day 1 of each cycle. Vincristine was administered at a dose of 1.4 mg/m^2 IV (maximum of 2 mg) on Day 1 of each cycle. Prednisone was administered at a dose of 100 mg orally on Days 1-5 of each cycle. All 4 drugs were administered either every 21 days for 8 cycles or every 14 days for 6 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Drug: Placebo
Placebo to bevacizumab was administered on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Baseline to end of the study (up to 4 years, 4 months)
PFS was defined as the time from the date of randomization to the date of disease progression (PD)/relapse, as determined by the investigator, or death from any cause, whichever occurred earlier. A patient with PD/relapse must meet at least 1 of the following criteria: (1) Appearance of any new lesion > 1.0 cm in the short axis during or at the end of therapy. (2) ≥ 50 % increase from nadir in the sum of the products of diameters (SPD, maximum diameter of a tumor x largest diameter perpendicular to the maximum diameter) of any previously involved nodes, in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be considered progressive disease, a lymph node with a diameter of the short axis < 1.0 cm must increase by ≥ 50% to a size of 1.5 x 1.5 cm or > 1.5 cm in the long axis. (3) ≥ 50 % increase in the greatest diameter of any previously identified node > 1.0 cm in its short axis or in the SPD of more than 1 node.
Baseline to end of the study (up to 4 years, 4 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Baseline to end of the study (up to 4 years, 4 months)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
Baseline to end of the study (up to 4 years, 4 months)
Overall Response (OR) Assessed According to the Revised Response Criteria for Malignant Lymphoma
Time Frame: At the end of treatment (Cycle 8, up to 12 months)
OR = a complete response (CR), an unconfirmed CR, or a partial response (PR). CR = Complete disappearance of disease and disease-related symptoms. All lymph nodes and nodal masses regressed on computed tomography (CT) to normal size (≤ 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and ≤ 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical examination, normal size by imaging, and disappearance of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease.
At the end of treatment (Cycle 8, up to 12 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Collaborators

Genentech, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2007

Primary Completion (Actual)

November 30, 2011

Study Completion (Actual)

November 30, 2011

Study Registration Dates

First Submitted

June 14, 2007

First Submitted That Met QC Criteria

June 14, 2007

First Posted (Estimate)

June 15, 2007

Study Record Updates

Last Update Posted (Actual)

July 25, 2017

Last Update Submitted That Met QC Criteria

June 26, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BO20603

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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