Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

Chimeric Anti-CD20 Monoclonal Antibody (Mabthera) in Remission Induction and Maintenance Treatment of Relapsed Follicular Non-Hodgkin's Lymphoma: A Phase III Randomized Clinical Trial - Intergroup Collaborative Study

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether chemotherapy is more effective with or without rituximab for relapsed non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying combination chemotherapy and rituximab to see how well they work compared to combination chemotherapy alone in treating patients with relapsed non-Hodgkin's lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: rituximab; Drug: CHOP regimen

Detailed Description

OBJECTIVES:

• Compare the response rate and quality of remission in patients with relapsed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab.
• Compare the event-free survival and overall survival of patients treated with these regimens.
• Determine the effect of rituximab as maintenance therapy on progression-free survival of these patients.

OUTLINE: This is a randomized, multicenter study.

• Induction: Patients are randomized to one of two treatment arms. Patients are stratified according to participating center, prior treatment with purine analogues, age, number of prior induction treatments and best response obtained (complete vs partial remission vs no change/progressive disease), time since diagnosis (less than 2 years vs more than 2 years), and bulky disease (less than 10 cm vs greater than 10 cm).

  • Arm I (closed as of 12/20/04): Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5 (CHOP chemotherapy). Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive CHOP chemotherapy as in arm I. Rituximab IV is administered 1 hour after prednisone and before the IV drugs.

• Maintenance: Patients who achieve partial or complete remission are then randomized to one of two treatment arms. Patients are stratified according to rituximab administration during induction (yes vs no), quality of the response (complete vs partial remission vs no change/progressive disease), and participating center.

  • Arm I: Patients receive no further therapy.
  • Arm II: Beginning 8 weeks after the last CHOP course, patients receive rituximab IV once every 3 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 4 months thereafter.

PROJECTED ACCRUAL: A total of 752 patients will be accrued for this study within 6 years.

• Study Type: Interventional
• Enrollment (Actual): 475
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Cancer Therapy Centre at Liverpool Hospital
    • Randwick, New South Wales, Australia, 2031
      • Institute of Oncology at Prince of Wales Hospital
    • Randwick, New South Wales, Australia, NSW 2031
      • Prince of Wales Private Hospital
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent's Hospital
    • Sydney, New South Wales, Australia, 2050
      • Sydney Cancer Centre at Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2217
      • St. George Hospital and Community Health Service
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Breast Centre at NSW Breast Cancer Institute
    • Wollongong, New South Wales, Australia, 2500
      • Wollongong Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Wesley Medical Centre
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Greenslopes, Queensland, Australia, 4120
      • Greenslopes Private Hospital
    • Townsville, Queensland, Australia, 4810
      • Townsville General Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital Cancer Centre
    • Ashford, South Australia, Australia, 5035
      • Ashford Cancer Centre
    • Bedford Park, South Australia, Australia, 5042
      • Flinder Medical Centres
    • Woodville, South Australia, Australia, 5011
      • Queen Elizabeth Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • St. John of God Hospital
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Coburg, Victoria, Australia, 3058
      • John Fawkner Hospital
    • East Melbourne, Victoria, Australia, 8006
      • Peter MacCallum Cancer Centre
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital
    • Geelong, Victoria, Australia, 3200
      • Geelong Hospital
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3181
      • Alfred Hospital
    • Mornington, Victoria, Australia, 3931
      • Garden Consulting Rooms
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Fremantle Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital - Perth
    • Perth, Western Australia, Australia, 6000
      • Mount Medical Centre
• Belgium
  • Antwerp, Belgium, 2020
    • Ziekenhuis Netwerk Antwerpen Middelheim
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, B-2650
    • Universitair Ziekenhuis Antwerpen
  • Ghent, Belgium, B-9000
    • Algemeen Ziekenhuis Sint Lucas
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
  • Roeselare, Belgium, 8800
    • H. Hartziekenhuis - Roeselaere.
  • Wilrijk, Belgium, 2610
    • Algemeen Ziekenhuis Sint-Augustinus
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre - Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute at University of Alberta
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • British Columbia Cancer Agency - Centre for the Southern Interior
    • Nanaimo, British Columbia, Canada, V9S 2B7
      • Nanaimo Cancer Clinic at Nanaimo Regional General Hospital
    • North Vancouver, British Columbia, Canada, V7L 2P9
      • Lions Gate Hospital
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Fraser Valley Cancer Centre at British Columbia Cancer Agency
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6ZB
      • Moncton Hospital
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Newfoundland Cancer Treatment and Research Foundation
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital of Barrie
    • Hamilton, Ontario, Canada, L8V 5C2
      • Margaret and Charles Juravinski Cancer Centre
    • Kingston, Ontario, Canada, K7L 5P9
      • Cancer Centre of Southeastern Ontario At Kingston General Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
    • Mississauga, Ontario, Canada, L5B 1B8
      • Trillium Health Centre - Mississauga Site
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Hospital Regional Cancer Centre - General Campus
    • St. Catharines, Ontario, Canada, L2R 5K3
      • Hotel Dieu Health Sciences Hospital - Niagara
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre
    • Thunder Bay, Ontario, Canada, P7A 7T1
      • Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre
    • Toronto, Ontario, Canada, M6R 1B5
      • St. Joseph's Health Centre - Toronto
    • Weston, Ontario, Canada, M9N 1N8
      • Humber River Regional Hospital - Weston
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre at Windsor Regional Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Cancer Centre at McGill University
    • Montreal, Quebec, Canada, H4L 2M1
      • Hopital Notre- Dame du CHUM
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint-Sacrement, Quebec
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet - Copenhagen University Hospital
  • Vejle, Denmark, 7100
    • Vejle Sygehus
• Egypt
  • Cairo, Egypt
    • National Cancer Institute of Egypt
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
• Hungary
  • Budapest, Hungary, 1125
    • National Institute of Oncology
• Italy
  • Aviano, Italy, 33081
    • Centro di Riferimento Oncologico - Aviano
• Netherlands
  • 's-Gravenhage, Netherlands, 2545 CH
    • HagaZiekenhuis
  • 's-Hertogenbosch, Netherlands, 5211 NL
    • Jeroen Bosch Ziekenhuis
  • Alkmaar, Netherlands, 1815 JD
    • Medisch Centrum Alkmaar
  • Almere, Netherlands, 1315RA
    • Ijselmeer Ziekenhuis - Zuiderzeeziekenhuis
  • Amersfont, Netherlands, 3016 CP
    • Meander Medisch Centrum
  • Amsterdam, Netherlands, 1091 HA
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands, 1007 MB
    • Vrije Universiteit Medisch Centrum
  • Amsterdam, Netherlands, 1006 AE
    • St. Lucas - Andreas Ziekenhuis
  • Amsterdam, Netherlands, 1034 CS
    • Boveny Ziekenhuis
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
  • Amsterdam, Netherlands, 1066 EC
    • Slotervaart Ziekenhuis
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum at University of Amsterdam
  • Amsterdam, Netherlands
    • Albert Schweitzerziekenhuis- Zwijndrecht
  • Amsterdam, Netherlands
    • Scheperziekenhuis
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuizen - Lokatie Lukas
  • Bergen-op-Zoom, Netherlands, 4624 VT
    • Ziekenhuis Lievensberg
  • Blaricum, Netherlands, 1261 AN
    • Streekziekenhuis Gooi-Noord
  • Breda, Netherlands, 4800 RL
    • Amphia Ziekenhuis - locatie Langendijk
  • Breda, Netherlands, 4818 CK
    • Amphia Ziekenhuis - locatie Molengracht
  • Brunssum, Netherlands, 6442 BE
    • Atrium Medical Centre - Brunssum
  • Capelle aan den Ijssel, Netherlands, 2906 ZC
    • IJsselland ziekenhuis
  • Delft, Netherlands, NL 2600 GA
    • Reinier de Graaf Group - Delft
  • Den Haag, Netherlands, 2566 MJ
    • Red Cross Hospital
  • Den Helder, Netherlands, 1782 GZ
    • Gemini Ziekenhuis
  • Deventer, Netherlands, 7415 CM
    • Deventer Ziekenhuisen
  • Dirksland, Netherlands, 3247 BW
    • Van Weel Bethesda Ziekenhuis
  • Drachten, Netherlands, NL-9200 DA
    • Nij Smellinghe
  • Eindhoven, Netherlands, 5631 BM
    • Diaconessenhuis Eindhoven
  • Enschede, Netherlands, 7500 KA
    • Medisch Spectrum Twente
  • Geldrop, Netherlands, NL-5664
    • St. Anna Ziekenhuis
  • Gorinchem, Netherlands
    • Beatrixziekenhuis
  • Gouda, Netherlands, 2803 HH
    • Groene Hart Ziekenhuis
  • Groningen, Netherlands
    • Martini Ziekenhuis
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Haarlem, Netherlands, 2000
    • Kennemer Gasthuis - Locatie EG
  • Haarlem, Netherlands, 2012 CE
    • Spaarne Ziekenhuis Haarlem
  • Harderwijk, Netherlands, 3840 AC
    • Ziekenhuis St Jansdal
  • Heerenveen, Netherlands, 8440 MA
    • Tjongerschans Ziekenhuis
  • Heerlen, Netherlands, 6419 PC
    • Atrium Medical Centre - Heerlen
  • Helmond, Netherlands, 5707-HA
    • Elkerliek Ziekenhuis
  • Hengelo, Netherlands, 7555 DL
    • Streekziekenhuis Midden-Twente
  • Hoorn, Netherlands, 1624 AR
    • Westfries Gasthuis
  • La Zierikzee, Netherlands, NL-4300
    • Zweedse Rode Kruis Ziekenhuis
  • Leeuwarden, Netherlands, 8934 AD
    • Medisch Centrum Leeuwarden - Zuid
  • Leiden, Netherlands, 2300 CA
    • Leiden University Medical Center
  • Leiden, Netherlands, 2300 RD
    • Diaconessenhuis Leiden
  • Leiderdorp, Netherlands, 2350 CC
    • Rijnland Ziekenhuis
  • Leidschendam, Netherlands, 2262 BA
    • Medisch Centrum Haaglanden Antoniushove
  • Maastricht, Netherlands, 6202 AZ
    • Academisch Ziekenhuis Maastricht
  • Meppel, Netherlands, NL-7940
    • Nederlandse Hervormde Diaconessenhuisinrichting
  • Nieuwegein, Netherlands, 3435 CM
    • Sint Antonius Ziekenhuis
  • Nijmegen, Netherlands, NL-6500 HB
    • Nijmegen Cancer Center at Radboud University Medical Center
  • Oss, Netherlands, 5340 BE
    • Ziekenhuis Bernhoven
  • Purmerend, Netherlands, 1440 AG
    • Waterlandziekenhuis
  • Roermond, Netherlands, 6043 CV
    • Saint Laurentius Ziekenhuis
  • Roosendaal, Netherlands, 4708 AE
    • Saint Franciscus Ziekenhuis
  • Rotterdam, Netherlands, 3000 CA
    • University Medical Center Rotterdam at Erasmus Medical Center
  • Rotterdam, Netherlands, 3045 PM
    • St. Franciscus Gasthuis
  • Rotterdam, Netherlands, 3075 AC
    • Medisch Centrum Rynmond-Zuid - Lokatie Zuider
  • Rotterdam, Netherlands, 3078 HT
    • Medisch Centrum Rynmond Zuid - Lokatie: Clara
  • Rotterdam, Netherlands, NL-3000
    • Havenziekenhiuis
  • Rotterdam, Netherlands, NL-3083
    • Ikazia Ziekenhuis
  • Sittard, Netherlands, 6131 BK
    • Maasland Hospital
  • Sliedrecht, Netherlands, NL-336
    • Albert Schweitzerziekenhuis- Sliedrecht
  • Spykenisse, Netherlands, NL-3200 GA
    • Ruwaard Van Putten Ziekenhuis
  • Stadskanaal, Netherlands, NL-9501
    • Ziekenhuis Refaja
  • Terneuzen, Netherlands, NL-4535
    • Ziekenhuis de Honte
  • Tiel, Netherlands, NL-4000
    • Rivierenland Tiel
  • Tilburg, Netherlands, 5022 GC
    • St. Elisabeth Ziekenhuis
  • Tilburg, Netherlands, 5042 AD
    • Twee Steden Ziekenhuis Vestiging Tilburg
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
  • Utrecht, Netherlands, NL-3563
    • Mesos Medisch Centrum - Overvecht
  • Utrecht, Netherlands
    • Oudenrijn Ziekenhuis
  • Veghel, Netherlands, NL-5461
    • St. Joseph Veghel
  • Veldhoven, Netherlands, 5500 MB
    • Maxima Medisch Centrum - locatie Eindhoven
  • Vlaardingen, Netherlands, NL-3130 GA
    • Holy-Ziekenhuis
  • Voorburg, Netherlands, 2275 CX
    • Reinier de Graaf Group - Voorburg
  • Weert Be, Netherlands, 6001
    • St. Jans Gasthuis Weert
  • Woerden, Netherlands, NL-3445
    • Hofpoort Ziekenhuis
  • Zaandam, Netherlands, 1502 DV
    • Zaans Medisch Centrum
  • Zeist, Netherlands, NL-3700
    • Lorentz Ziekenhuis
  • Zoetermeer, Netherlands, NL-2700
    • 't Lange Land Ziekenhuis
  • Zwolle, Netherlands, 8000 GK
    • Isala Klinieken - locatie Sophia
  • Zwolle, Netherlands, NL-8000 GM
    • Isala Klinieken - Locatie Weezenlanden
• New Zealand
  • Auckland, New Zealand, 3
    • University of Auckland School of Medicine
  • Christchurch, New Zealand, 1
    • Christchurch Hospital
  • Hamilton, New Zealand, 2020
    • Waikato Hospital
• Norway
  • Bergen, Norway, N-5021
    • Haukeland Hospital - University of Bergen
  • Oslo, Norway, N-0310
    • Norwegian Radium Hospital
  • Trondheim, Norway, 7006
    • St. Olavs University Hospital
• Poland
  • Warsaw, Poland, 02-781
    • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
• Portugal
  • Lisbon, Portugal, 1099-023 Codex
    • Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.
• Slovakia
  • Bratislava, Slovakia, 833 10
    • National Cancer Institute - Bratislava
• Slovenia
  • Ljubljana, Slovenia, Sl-1000
    • Institute of Oncology - Ljubljana
• South Africa
  • Brooklyn Square, South Africa, 1577
    • Mary Potter Oncology Centre
  • Johannesburg, South Africa, 2121
    • Sandton Oncology Centre
  • Johannesburg, South Africa, 2193
    • Medical Oncology Centre of Rosebank
  • Parktown, South Africa, 2193
    • Johannesburg General Hospital
• Sweden
  • Gothenburg (Goteborg), Sweden, S-413 45
    • Sahlgrenska University Hospital at Gothenburg University
  • Linkoping, Sweden, S-581 85
    • University Hospital of Linkoping
  • Lulea, Sweden, 95128
    • Sunderby Hospital
  • Lund, Sweden, S-22185
    • Lund University Hospital
  • Orebro, Sweden, 70185
    • Orebro University Hospital
  • Stockholm, Sweden, S-141 86
    • Karolinska University Hospital - Huddinge
  • Sundsvall, Sweden, 85186
    • Sundsvall Hospital
  • Umea, Sweden, S-901 85
    • Umeå Universitet
• United Kingdom
  • Chichester, United Kingdom, P019 4SE
    • Saint Richards Hospital
  • Hull, United Kingdom, HU3 2KZ
    • Hull Royal Infirmary
  • Kettering, Northants, United Kingdom, NNI6 8UZ
    • Kettering General Hosptial
  • Stafford, United Kingdom, ST16 3SA
    • Staffordshire General Hospital
  • Swindon,, United Kingdom, SN1 4JU
    • Great Western Hospital
  • England
    • Aylesbury-Buckinghamshire, England, United Kingdom, HP21 8AL
      • Stoke Mandeville Hospital
    • Bath, England, United Kingdom, BA1 3NG
      • Royal United Hospital
    • Birmingham, England, United Kingdom, B18 7QH
      • City Hospital - Birmingham
    • Birmingham, England, United Kingdom, B9 5SS
      • Birmingham Heartlands Hospital
    • Blackpool, England, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital
    • Bournemouth, England, United Kingdom, BH7 7DW
      • Royal Bournemouth Hospital
    • Bradford, England, United Kingdom, BD9 6RJ
      • Bradford Hospitals NHS Trust
    • Bristol, England, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology Centre
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
    • Canterbury, England, United Kingdom, CT2 7NR
      • Conquest Hospital
    • Canterbury, England, United Kingdom, CT2 7NR
      • Kent and Canterbury Hospital
    • Carshalton, England, United Kingdom, SM5 1AA
      • St Helier Hospital
    • Cheltenham, England, United Kingdom, GL53 7AN
      • Cheltenham General Hospital
    • Chester, England, United Kingdom, CH2 1UL
      • Countess of Chester Hospital
    • Colchester, England, United Kingdom, C03 3NB
      • Essex County Hospital
    • Doncaster, England, United Kingdom, DN2 5LT
      • Doncaster Royal Infirmary
    • Dudley, England, United Kingdom, DY1 2HQ
      • Russells Hall Hospital
    • Exeter, England, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
    • Gateshead, England, United Kingdom, NE9 6SX
      • Queen Elizabeth Hospital
    • Grimsby, England, United Kingdom, DN33 2BA
      • Diana Princess of Wales Hospital
    • Hampstead, London, England, United Kingdom, NW3 2QG
      • Royal Free and University College Medical School
    • Huntingdon, England, United Kingdom, PE18 6NT
      • Hinchingbrooke Hospital
    • Ilford, Essex, England, United Kingdom, IG3 8YB
      • King George Hospital
    • Leeds, England, United Kingdom, LS1 3EX
      • Leeds General Infirmary at Leeds Teaching Hospital NHS Trust
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • Liverpool, England, United Kingdom, L9 7AL
      • Aintree University Hospital
    • Liverpool, England, United Kingdom, L69 3GA
      • Royal Liverpool University Hospital
    • London, England, United Kingdom, SW17 0QT
      • St. George's Hospital
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • London, England, United Kingdom, SE1 9RT
      • Guy's and St. Thomas' Hospitals NHS Foundation Trust
    • London, England, United Kingdom, SW17 ORE
      • St. Georges Hospital Medical School
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Foundation Trust - London
    • London, England, United Kingdom, WC1E 6AU
      • University College Hospital
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology NHS Trust
    • Middlesbrough, England, United Kingdom, TS4 3BW
      • James Cook University Hospital
    • Newcastle-Upon-Tyne, England, United Kingdom, NE7 7DN
      • Newcastle Upon Tyne Hospitals NHS Trust
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Norwich, England, United Kingdom, NR1 3SR
      • Norfolk and Norwich University Hospital
    • Oxford, England, United Kingdom, 0X3 9DU
      • Oxford Radcliffe Hospital
    • Portsmouth, England, United Kingdom, P03 6AD
      • Portsmouth Hospitals NHS Trust
    • Prescot Merseyside, England, United Kingdom, L35 5DR
      • Whiston Hospital
    • Preston, England, United Kingdom, PR2 9HT
      • Royal Preston Hospital
    • Reading, England, United Kingdom, RG1 5AN
      • Berkshire Cancer Centre at Royal Berkshire Hospital
    • Romford, England, United Kingdom, RM7 OBE
      • Oldchurch Hospital
    • Royal Tunbridge Wells, Kent, England, United Kingdom, TN2 4QJ
      • Pembury Hospital
    • Salisbury, England, United Kingdom, SP2 8BJ
      • Salisbury District Hospital
    • Scunthorpe, England, United Kingdom, DN15 7BH
      • Scunthorpe General Hospital
    • Sheffield, England, United Kingdom, S1O 2SJ
      • Cancer Research Centre at Weston Park Hospital
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
    • Stoke-On-Trent, England, United Kingdom, ST4 7LN
      • North Staffs Royal Infirmary
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust - Surrey
    • Swansea, England, United Kingdom, SA 2 8QA
      • Singleton Hospital
    • Taunton Somerset, England, United Kingdom, TA1 5DA
      • Taunton and Somerset Hospital
    • Torquay Devon, England, United Kingdom, TQ2 7AA
      • Torbay Hospital
    • Uxbridge, England, United Kingdom, UB8 3NN
      • Hillingdon Hospital
    • West Bromwich, England, United Kingdom, B71 4HJ
      • Sandwell General Hospital
    • Winchester, England, United Kingdom, SO22 5DG
      • Royal Hampshire County Hospital
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Belfast City Hospital Trust
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Western General Hospital
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Western Infirmary
    • Glasgow, Scotland, United Kingdom, G4 0SF
      • Royal Infirmary - Castle
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Southern General Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 2TL
      • Velindre Cancer Center at Velinde Hospital
    • Cardiff, Wales, United Kingdom, CF14 4XN
      • University Hospital of Wales
    • Newport Gwent, Wales, United Kingdom, NP9 2UB
      • Royal Gwent Hospital
    • Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
      • Glan Clywd District General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven stage III or IV follicular non-Hodgkin's lymphoma (NHL)

  • Relapsed after or no response (no change/progressive disease) to no more than 2 adequate non-anthracycline-containing systemic chemotherapy regimens
  • At least 2 months of single-agent therapy (e.g., chlorambucil) AND/OR
  • At least 2 consecutive courses of polychemotherapy (e.g., cyclophosphamide, vincristine, and prednisone) or purine analogues
• Complete or partial remission or no change for at least 4 weeks after completion of prior therapy OR progression during one of a maximum of 2 prior therapy regimens
• CD20 positive
• At least 1 bidimensionally measurable mass
• No greater than 10,000,000/mL circulating tumor cells
• IgG levels at least 3 g/L
• No low-grade NHL transformed into intermediate- or high-grade NHL
• No symptomatic CNS lymphoma
• No bone marrow involvement only NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 2.5 times ULN

Renal:

• Creatinine less than 2.5 times ULN
• BUN less than 2.5 times ULN

Cardiovascular:

• No severe cardiac disease (i.e., severe heart failure requiring symptomatic treatment)

Pulmonary:

• No severe pulmonary disease

Other:

• No severe neurologic or psychiatric disease
• No severe metabolic disease
• Not pregnant
• Fertile patients must use effective contraception
• No prior malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other cancer curatively treated with surgical therapy
• HIV negative
• No uncontrolled asthma or allergy requiring steroids
• No known hypersensitivity or prior anaphylactic reaction to murine proteins or any component of study drug

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior rituximab
• No prior allogeneic or autologous peripheral blood stem cell transplantation
• Concurrent filgrastim (G-CSF) for stem cell mobilization allowed

Chemotherapy:

• See Disease Characteristics
• No prior anthracyclines or mitoxantrone
• No concurrent chemotherapy for stem cell mobilization

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response to treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	from randomization
Progression Free survival	from randomization

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: NCIC Clinical Trials Group; Stichting Hemato-Oncologie voor Volwassenen Nederland; Nordic Lymphoma Group; Lymphoma Trials Office; Australasian Leukaemia and Lymphoma Group
• Investigators: Study Chair: M. H. J. Van Oers, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Study Chair: Robert Marcus, MD, Cambridge University Hospitals NHS Foundation Trust; Study Chair: Max M. Wolf, MD, Peter MacCallum Cancer Centre, Australia; Study Chair: Richard J. Klasa, MD, British Columbia Cancer Agency; Study Chair: Eva K. Kimby, MD, PhD, Karolinska Institutet

Publications and helpful links

General Publications

• Deconinck E, Miadi-Fargier H, Pen CL, Brice P. Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation. Pharmacoeconomics. 2010;28(1):35-46. doi: 10.2165/11314070-000000000-00000.
• Pompen M, Huijgens PC, et al.: Cost-effectiveness of rituximab for maintenance in patients with follicular non-Hodgkin's lymphoma in the Dutch setting. [Abstract] Blood 112 (11): A-2364, 2008.
• Van Oers MH, Hagenbeek A, Van Glabbeke M, Teodorovic I. Chimeric anti-CD20 monoclonal antibody (Mabthera) in remission induction and maintenance treatment of relapsed follicular non-Hodgkin's lymphoma: a phase III randomized clinical trial--Intergroup Collaborative Study. Ann Hematol. 2002 Oct;81(10):553-7. doi: 10.1007/s00277-002-0548-2. Epub 2002 Oct 17. No abstract available.
• van Oers MH, Tonnissen E, Van Glabbeke M, Giurgea L, Jansen JH, Klasa R, Marcus RE, Wolf M, Kimby E, Vranovsky A, Holte H, Hagenbeek A, van der Reijden BA. BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study. J Clin Oncol. 2010 May 1;28(13):2246-52. doi: 10.1200/JCO.2009.25.0852. Epub 2010 Apr 5.
• van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. doi: 10.1200/JCO.2009.26.5827. Epub 2010 May 3.
• van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. doi: 10.1182/blood-2006-05-021113. Epub 2006 Jul 27.
• Mattiola I, Mantovani A, Locati M. The tetraspan MS4A family in homeostasis, immunity, and disease. Trends Immunol. 2021 Sep;42(9):764-781. doi: 10.1016/j.it.2021.07.002. Epub 2021 Aug 9.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 1999
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): July 19, 2017

Study Registration Dates

• First Submitted: January 21, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: stage IV grade 3 follicular lymphoma; recurrent grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine
• Other Study ID Numbers: EORTC-20981 (Other Identifier: EORTC); ALLG-NHLLOW4 (Other Identifier: ALLG); BNLI-EORTC-20981 (Other Identifier: BNLI); HOVON-H039 (Other Identifier: HOVON); CAN-NCIC-LY7 (Other Identifier: NCIC CTG); NORDIC-EORTC-20981 (Other Identifier: NLG)

Drug and device information, study documents

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