RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating stage III or stage IV Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have stage III or stage IV Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult lymphocyte depletion Hodgkin's lymphoma adult mixed cellularity Hodgkin's lymphoma adult nodular sclerosis Hodgkin's lymphoma stage III adult Hodgkin's lymphoma stage IV adult Hodgkin's lymphoma	Drug: bleomycin  Drug: cyclophosphamide  Drug: dacarbazine  Drug: doxorubicin  Drug: etoposide  Drug: filgrastim  Drug: pegfilgrastim  Drug: prednisone  Drug: procarbazine  Drug: vinblastine  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare event-free survival of patients with stage III or IV Hodgkin's lymphoma treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone vs doxorubicin, bleomycin, vinblastine, and dacarbazine.
• Compare complete response, disease-free survival, and overall survival of patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Compare occurrence of second malignancies in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to International Prognostic Score (3 vs 4 or more) and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I (BEACOPP): Patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV on day 1; etoposide IV over 30 minutes on days 1-3; oral procarbazine on days 1-7; oral prednisone on days 1-14; and vincristine IV and bleomycin IV or intramuscularly (IM) on day 8. Patients may receive dexamethasone in place of prednisone. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover or pegfilgrastim SC on day 9 only. Treatment repeats every 22 days for 8 courses (4 courses escalated dose followed by 4 courses baseline dose) in the absence of disease progression or unacceptable toxicity.
• Arm II (ABVD): Patients receive doxorubicin IV over 5 minutes, bleomycin IV or IM, vinblastine IV, and dacarbazine IV over 5-10 minutes on days 1 and 15. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at the end of therapy, and then annually for 10 years.

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 550 patients (225 per treatment arm) will be accrued for this study within 5.5 years.

Ages Eligible for Study:  16 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma
• No lymphocyte predominant, nodular type (nodular paragranuloma)
• Clinical stage III or IV disease
• At least 1 bidimensionally measurable target lesion or extranodal lesion
• International Prognostic Score of at least 3

PATIENT CHARACTERISTICS: Age

• 16 to 60

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 2,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic

• No prior uncontrolled hepatitis B viral infection
• Bilirubin no greater than 2.5 times normal (unless due to Hodgkin's lymphoma)

Renal

• Creatinine no greater than 2.0 mg/dL (unless due to Hodgkin's lymphoma)

Cardiovascular

• No severe cardiac disease that would limit normal life expectancy or preclude study
• LVEF at least 50%

Pulmonary

• No severe pulmonary disease that would limit normal life expectancy or preclude study
• Respiratory function at least 30%

Other

• HIV negative
• HTLV1 negative
• No severe active infection
• No severe neurological or metabolic disease that would limit normal life expectancy or preclude study
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude study
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior therapy for Hodgkin's lymphoma

Australia, Victoria
      Peter MacCallum Cancer Centre, East Melbourne,  Victoria,  3002,  Australia; Recruiting
Australia, Western Australia
      Royal Perth Hospital, Perth,  Western Australia,  6000,  Australia; Recruiting
Belgium
      Algemeen Ziekenhuis Sint Lucas, Ghent,  B-9000,  Belgium; Recruiting
      AZ Sint-Jan, Brugge,  8000,  Belgium; Recruiting
      Centre Hospitalier Notre Dame - Reine Fabiola, Charleroi,  6000,  Belgium; Recruiting
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium; Recruiting
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium; Recruiting
      H. Hartziekenhuis V.Z.W., Roeselare,  8800,  Belgium; Recruiting
      Hopital de Jolimont, Haine-Saint-Paul,  7100,  Belgium; Recruiting
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
      Ziekenhuis Network Antwerpen Middelheim, Antwerp,  2020,  Belgium; Recruiting
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada; Recruiting
      Tom Baker Cancer Centre - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada; Recruiting
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada; Recruiting
      Centre Hospitalier De Dunkerque - CHD, Winnipeg,  Manitoba,  R3E 0V9,  Canada; Recruiting
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada; Recruiting
Canada, Ontario
      Cancer Care Ontario - Windsor Regional Cancer Centre, Windsor,  Ontario,  N8W 2X3,  Canada; Recruiting
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting
      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada; Recruiting
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2L-4M1,  Canada; Recruiting
      Centre Hospitalier Universitaire de Quebec, Quebec City,  Quebec,  G1R 2J6,  Canada; Recruiting
      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada; Recruiting
      Hopital du Saint-Sacrement, Quebec, Quebec City,  Quebec,  G1S 4L8,  Canada; Recruiting
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada; Recruiting
Canada, Saskatchewan
      Saskatoon Cancer Centre, Saskatoon,  Saskatchewan,  S7N 4H4,  Canada; Recruiting
Croatia
      University Hospital Rebro, Zagreb,  41000,  Croatia; Recruiting
France
      C.H. Bourg En Bresse, Bourg-en-Bresse,  01012,  France; Recruiting
      Centre Antoine Lacassagne, Nice,  06189,  France; Recruiting
      Centre Henri Becquerel, Rouen,  76038,  France; Recruiting
      Centre Hospital Regional Universitaire de Limoges, Limoges,  87042,  France; Recruiting
      Centre Hospitalier d'Annecy, Annecy,  74011 Cedex,  France; Recruiting
      Centre Hospitalier de Meaux, Meaux,  77104,  France; Recruiting
      Centre Hospitalier de Mulhouse, Mulhouse,  68051,  France; Recruiting
      Centre Hospitalier de Valenciennes, Valenciennes,  59300,  France; Recruiting
      Centre Hospitalier Lyon Sud, Pierre-Benite,  69495,  France; Recruiting
      Centre Hospitalier Marc Jacquet, Melun,  77011,  France; Recruiting
      Centre Hospitalier Regional de Chambery, Chambery,  73011,  France; Recruiting
      Centre Hospitalier Regional et Universitaire de Lille, Lille,  59037,  France; Recruiting
      Centre Hospitalier Sud Francilien - Site Corbeil, Corbeil,  91100,  France; Recruiting
      Centre Hospitalier Universitaire Henri Mondor, Creteil,  94010,  France; Recruiting
      Centre Hospitalier Valence, Valence,  26000,  France; Recruiting
      Centre Leon Berard, Lyon,  69373,  France; Recruiting
      Centre Medico-Chirurgical Foch, Suresnes,  92151,  France; Recruiting
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France; Recruiting
      Centre Regional Francois Baclesse, Caen,  14076,  France; Recruiting
      Centre Rene Huguenin, Saint Cloud,  92211,  France; Recruiting
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France; Recruiting
      CHU de Caen, Caen,  14033,  France; Recruiting
      CHU de Nancy - Hopitaux de Brabois, Vandoeuvre-les-Nancy,  54511,  France; Recruiting
      CHU Pitie-Salpetriere, Paris,  75651,  France; Recruiting
      Hopital Andre Mignot, Le Chesnay,  78157,  France; Recruiting
      Hopital Antoine Beclere, Clamart,  92141,  France; Recruiting
      Hopital Bellevue, Saint-Etienne,  42055,  France; Recruiting
      Hopital Cochin, Paris,  75674,  France; Recruiting
      Hopital de Saint Germain-en-Laye, Saint-Germain-en-Laye,  78104,  France; Recruiting
      Hopital d'Instruction des Armees Percy, Clamart,  92140,  France; Recruiting
      Hopital Du Bocage, Dijon,  21034,  France; Recruiting
      Hopital Edouard Herriot, Lyon,  69437,  France; Recruiting
      Hopital Haut Leveque, Pessac,  33604,  France; Recruiting
      Hopital Louis Pasteur, Colmar,  68024,  France; Recruiting
      Hopital Necker, Paris,  75743,  France; Recruiting
      Hopital Notre-Dame de Bon Secours, Metz,  55038,  France; Recruiting
      Hopital Paul Brousse, Villejuif,  94804,  France; Recruiting
      Hopital Rene Dubos, Pontoise,  95300,  France; Recruiting
      Hopital Saint Antoine, Paris,  75571,  France; Recruiting
      Hopital Saint-Louis, Paris,  75475,  France; Recruiting
      Hopital Universitaire Hautepierre, Strasbourg,  67098,  France; Recruiting
      Hotel Dieu de Paris, Paris,  75181,  France; Recruiting
      Institut Bergonie, Bordeaux,  33076,  France; Recruiting
      Institut Curie - Section Medicale, Paris,  75248,  France; Recruiting
      Institut Gustave Roussy, Villejuif,  F-94805,  France; Recruiting
      Institut J. Paoli and I. Calmettes, Marseille,  13273,  France; Recruiting
      Institut Jean Godinot, Reims,  51056,  France; Recruiting
      Institut Prive de Cancerologie, Grenoble,  38100,  France; Recruiting
      Polyclinique Bordeaux Nord Aquitaine, Boucher,  33300,  France; Recruiting
      Polyclinique Du Parc, Caen,  14052,  France; Recruiting
Hungary
      National Institute of Oncology, Budapest,  1122,  Hungary; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands; Recruiting
      Atrium Medical Centre - Heerlen, HEERLEN,  6419 PC,  Netherlands; Recruiting
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Leyenburg Ziekenhuis, S. Gravenhage,  2545 CH,  Netherlands; Recruiting
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands; Recruiting
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands; Recruiting
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands; Recruiting
      Reinier de Graaf Group - Delft, Delft,  NL 2600 GA,  Netherlands; Recruiting
      University Medical Center Groningen, Groningen,  9713 EZ,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
      University Medical Center Utrecht, Utrecht,  3584 CX,  Netherlands; Recruiting
Spain
      Hospital Clinic de Barcelona, Barcelona,  08036,  Spain; Recruiting
      Hospital de la Santa Cruz I Sant Pau, Barcelona,  08025,  Spain; Recruiting
Sweden
      Karolinska University Hospital - Huddinge, Stockholm,  S-141 86,  Sweden; Recruiting
      Lund University Hospital, Lund,  S-22185,  Sweden; Recruiting
      Sahlgrenska University Hospital at Gothenburg University, Gothenburg (Goteborg),  S-413 45,  Sweden; Recruiting
      Umea Universitet, Umea,  S-901 85,  Sweden; Recruiting
      University Hospital of Linkoping, Linkoping,  S-581 85,  Sweden; Recruiting
      Uppsala University Hospital, Uppsala,  S-75185,  Sweden; Recruiting
United Kingdom, England
      Cancer Research Centre at Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom; Recruiting
      Hull Royal Infirmary, Hull,  England,  HU3 2KZ,  United Kingdom; Recruiting
      Kent and Canterbury Hospital, Canterbury,  England,  CT2 7NR,  United Kingdom; Recruiting
      Kettering General Hosptial, Kettering, Northants,  England,  NNI6 8UZ,  United Kingdom; Recruiting
      Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom; Recruiting
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  United Kingdom; Recruiting
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom; Recruiting
      Queen Elizabeth Hospital at University of Birmingham, Birmingham,  England,  B15 2TH,  United Kingdom; Recruiting
      Raigmore Hospital, Birmingham,  England,  B15 2TH,  United Kingdom; Recruiting
      Staffordshire General Hospital, Stafford,  England,  ST16 3SA,  United Kingdom; Recruiting
      University College London Medical School, London,  England,  WC1E 6HX,  United Kingdom; Recruiting

Study chairs or principal investigators

Patrice P. Carde, MD,  Institut Gustave Roussy   
David C. Linch,  Study Chair,  University College London Medical School   
Marine Divine, MD,  Study Chair,  Centre Hospitalier Universitaire Henri Mondor   
Anna Sureda,  Study Chair,  Hospital de la Santa Cruz I Sant Pau   
Ralph M. Meyer, MD, FRCPC,  Study Chair,  Margaret and Charles Juravinski Cancer Centre   
David Ma, MD,  St. Vincent's Hospital   
Devinder Gill, MD,  Princess Alexandra Hospital   
Bengt Glimelius, MD,  Study Chair,  Uppsala University Hospital   

Study ID Numbers:  CDR0000258125; EORTC-20012; GELA-EORTC-20012; BNLI-EORTC-20012; GELCAB-EORTC-20012; NORDICLG-EORTC-20012; CAN-NCIC-EORTC-20012; ALLG-HD04; NCT00049595
Record last reviewed:  March 2005
Last Updated:  April 4, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049595
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08