Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma

BEACOPP (4 Cycles Escalated + 4 Cycles Baseline) Versus ABVD (8 Cycles) In Stage III & IV Hodgkin's Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclophosphamide; Drug: prednisone; Drug: etoposide; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Drug: dacarbazine; Drug: procarbazine hydrochloride; Drug: vinblastine sulfate; Biological: bleomycin sulfate; Biological: pegfilgrastim; Drug: BEACOPP regimen; Drug: ABVD regimen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 552
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2606
      • Canberra Hospital
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Cancer Care Centre at Nepean Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Institute for Cancer Research at Westmead Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital - Melbourne
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Belgium
  • Antwerp, Belgium, 2020
    • Ziekenhuis Netwerk Antwerpen Middelheim
  • Brugge, Belgium, 8000
    • AZ Sint-Jan
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Brussels, Belgium, 1070
    • Hopital Universitaire Erasme
  • Brussels, Belgium, B 1020
    • Centre Hospitalier Universitaire Brugmann
  • Charleroi, Belgium, 6000
    • Centre Hospitalier Notre Dame - Reine Fabiola
  • Edegem, Belgium, B-2650
    • Universitair Ziekenhuis Antwerpen
  • Ghent, Belgium, B-9000
    • Algemeen Ziekenhuis Sint Lucas
  • Haine Saint Paul, Belgium, 7100
    • Hôpital de Jolimont
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
  • Liege, Belgium, 4000
    • Centre Hospitalier Regional de la Citadelle
  • Roeselare, Belgium, 8800
    • H. Hartziekenhuis - Roeselaere
  • Yvoir, Belgium, 5530
    • Clinique Universitaire De Mont-Godinne
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre - Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute at University of Alberta
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Centre Hospitalier De Dunkerque - CHD
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6ZB
      • Moncton Hospital
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Doctor H. Bliss Murphy Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Cancer Centre
  • Ontario
    • 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
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Regional Cancer Centre - General Campus
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Edmond Odette Cancer Centre at Sunnybrook
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre at Windsor Regional Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hôpital Charles Lemoyne
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill Cancer Centre at McGill University
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre-Dame du CHUM
    • Montreal, Quebec, Canada, H2L-4M1
      • CHUM - Hotel Dieu Hospital
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint-Sacrement - Quebec
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• Croatia
  • Zagreb, Croatia, 41000
    • University Hospital Rebro
• Czechia
  • Prague, Czechia, 14000
    • Thomayer's University Hospital
• France
  • Annecy, France, 74011 Cedex
    • Centre Hospitalier d'Annecy
  • Bayonne, France, 64100
    • Centre Hospitalier de la Côte Basque
  • Besancon, France, 25030
    • Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Boucher, France, 33300
    • Polyclinique Bordeaux Nord Aquitaine
  • Bourg En Bresse, France, 01012
    • C.H. Bourg En Bresse
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Caen, France, 14033
    • CHU de Caen
  • Caen, France, 14052
    • Polyclinique du Parc
  • Chambery, France, 73011
    • Centre Hospitalier Regional de Chambery
  • Clamart, France, 92141
    • Hopital Antoine Beclere
  • Clamart, France, 92140
    • Hôpital d'Instruction des Armées PERCY
  • Clermont-Ferrand, France, 63003
    • CHR Clermont Ferrand, Hotel Dieu
  • Colmar, France, 68024
    • Hôpital Louis Pasteur
  • Corbeil, France, 91100
    • Centre Hospitalier Sud Francilien - Site Corbeil
  • Creteil, France, 94010
    • Centre Hospitalier Universitaire Henri Mondor
  • Dijon, France, 21034
    • Hopital Du Bocage
  • Grenoble, France, 38100
    • Institut Prive de Cancerologie
  • Le Chesnay, France, 78157
    • Hôpital André Mignot
  • Lille, France, 59037
    • Centre Hospitalier Regional et Universitaire de Lille
  • Lille, France, 59000
    • Hopital Saint Antoine Lille
  • Limoges, France, 87042
    • Centre Hospital Regional Universitaire de Limoges
  • Lyon, France, 69437
    • Hopital Edouard Herriot - Lyon
  • Lyon, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13273
    • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
  • Meaux, France, 77104
    • Centre Hospitalier de Meaux
  • Melun, France, 77011
    • Centre Hospitalier Marc Jacquet
  • Metz, France, 55038
    • Hopital Notre-Dame de Bon Secours
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Mulhouse, France, 68051
    • Centre Hospitalier de Mulhouse
  • Nice, France, F-06202
    • Hopital de l'Archet CHU de Nice
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75651
    • CHU Pitié-Salpêtrière
  • Paris, France, 75674
    • Hopital Cochin
  • Paris, France, 75571
    • Hopital Saint Antoine
  • Paris, France, 75743
    • Hôpital Necker
  • Paris, France, 75181
    • Hotel Dieu de Paris
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Paris, France, 75248
    • Institut Curie Hopital
  • Pessac, France, 33604
    • Hôpital Haut Lévêque
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Pontoise, France, 95300
    • Hôpital René Dubos
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rennes, France, 35056
    • Hopital Sud
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint Cloud, France, 92211
    • Centre René Huguenin
  • Saint Etienne, France, 42055
    • CHU Sainte-Etienne - Hopital Bellevue
  • Saint Germain-en-Laye, France, 78104
    • Hopital de Saint Germain-en-Laye
  • Strasbourg, France, 67098
    • Hopital Universitaire Hautepierre
  • Suresnes, France, 92151
    • Hôpital Foch
  • Valence, France, 26000
    • Centre Hospitalier Valence
  • Valenciennes, France, 59300
    • Centre Hospitalier de Valenciennes
  • Vandoeuvre-Les-Nancy, France, 54511
    • CHU de Nancy - Hopitaux de Brabois
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
  • Villejuif, France, 94804
    • Hopital Paul Brousse
• Hungary
  • Budapest, Hungary, 1122
    • National Institute of Oncology
• Netherlands
  • 's-Gravenhage, Netherlands, 2545 CH
    • HagaZiekenhuis - Locatie Leyenburg
  • 's-Hertogenbosch, Netherlands, 5211 NL
    • Jeroen Bosch ziekenhuis
  • Amersfoort, Netherlands, 3816 CP
    • Meander Medisch Centrum
  • Amsterdam, Netherlands, 1091 HA
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum at University of Amsterdam
  • Delft, Netherlands, NL 2600 GA
    • Reinier de Graaf Group - Delft
  • Enschede, Netherlands, 7500 KA
    • Medisch Spectrum Twente
  • Groningen, Netherlands, 9713 EZ
    • University Medical Center Groningen
  • Heerlen, Netherlands, 6419 PC
    • Atrium Medical Centre - Heerlen
  • Leiden, Netherlands, 2300 CA
    • Leiden University Medical Center
  • Maastricht, Netherlands, 6202 AZ
    • Academisch Ziekenhuis Maastricht
  • Nijmegen, Netherlands, NL-6500 HB
    • Universitair Medisch Centrum St. Radboud - Nijmegen
  • Roermond, Netherlands, 6043 CV
    • Saint Laurentius Ziekenhuis
  • Rotterdam, Netherlands, 3008 AE
    • Daniel Den Hoed Cancer Center at Erasmus Medical Center
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• New Zealand
  • Auckland, New Zealand, 1
    • Auckland City Hospital
  • Hamilton, New Zealand, 2020
    • Waikato Hospital
• Poland
  • Warsaw, Poland, 02-781
    • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08025
    • Hospital de la Santa Cruz i Sant Pau
  • Barcelona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
• Sweden
  • Gothenburg (Goteborg), Sweden, S-413 45
    • Sahlgrenska University Hospital
  • Linkoping, Sweden, S-581 85
    • University Hospital of Linkoping
  • Lund, Sweden, S-22185
    • Lund University Hospital
  • Stockholm, Sweden, S-141 86
    • Karolinska University Hospital - Huddinge
  • Umea, Sweden, S-901 85
    • Umeå Universitet
  • Uppsala, Sweden, S-75185
    • Uppsala University Hospital
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
    • Birmingham, England, United Kingdom, B15 2TH
      • Raigmore Hospital
    • Canterbury, England, United Kingdom, CT2 7NR
      • Kent and Canterbury Hospital
    • Hull, England, United Kingdom, HU3 2KZ
      • Hull Royal Infirmary
    • Kettering, England, United Kingdom, NNI6 8UZ
      • Kettering General Hosptial
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • London, England, United Kingdom, WC1E 6HX
      • Middlesex Hospital
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital NHS Trust
    • Sheffield, England, United Kingdom, S1O 2SJ
      • Cancer Research Centre at Weston Park Hospital
    • Stafford, England, United Kingdom, ST16 3SA
      • Staffordshire General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 58 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ABVD; 8 cycles of ABVD	Drug: doxorubicin hydrochloride; Drug: dacarbazine; Drug: vinblastine sulfate; Biological: bleomycin sulfate; Drug: ABVD regimen
Experimental: BEACOPP; 4 cycles of BEACOPP Escalated + 4 cycles of BEACOPP Baseline	Drug: cyclophosphamide; Drug: prednisone; Drug: etoposide; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Biological: filgrastim; Drug: procarbazine hydrochloride; Biological: bleomycin sulfate; Biological: pegfilgrastim; Drug: BEACOPP regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival	from randomization to early discontinuation of protocol treatment, no CR/CRu after 8 cycles, relapse, progression or death

Secondary Outcome Measures

Outcome Measure	Time Frame
Complete response as assessed by Cheson criteria adapted to Hodgkin's lymphoma	from randomization till end of treatment
Disease-free survival in patients with complete response	from the day of first documentation of CR to the day of relapse
Overall survival	from the date of randomization to the date of death
Quality of life as assessed by European Organization for Research of the Treatment of Cancer (EORTC) Quality of Life Questionnaire (QoLQ) C30 version 3.0	from one week prior to randomization till 10 years after end of treatment or death

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: NCIC Clinical Trials Group; Nordic Lymphoma Group; Lymphoma Trials Office; Australasian Leukaemia and Lymphoma Group; Lymphoma Study Association; Grup per l'Estudi dels Limfomes de Catalunya i Balears
• Investigators: Study Chair: Patrice P. Carde, MD, Gustave Roussy, Cancer Campus, Grand Paris; Study Chair: David C. Linch, Middlesex Hospital; Study Chair: Marine Divine, MD, Centre Hospitalier Universitaire Henri Mondor; Study Chair: Anna Sureda, Hospital de la Santa Cruz i Sant Pau; Study Chair: David Ma, MD, St Vincent's Hospital; Study Chair: Devinder Gill, MD, Princess Alexandra Hospital; Study Chair: Bengt Glimelius, MD, Uppsala University Hospital; Study Chair: Ralph M. Meyer, MD, FRCPC, Margaret and Charles Juravinski Cancer Centre

Publications and helpful links

General Publications

• Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score >/= 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. doi: 10.1200/JCO.2015.64.5648. Epub 2016 Apr 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2002
• Primary Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: November 12, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 8, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; adult lymphocyte depletion Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; 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; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Prednisone; Doxorubicin; Liposomal doxorubicin; Vincristine; Dacarbazine; Bleomycin; Vinblastine; Procarbazine
• Other Study ID Numbers: EORTC-20012 (Other Identifier: EORTC); GELA-EORTC-20012 (Other Identifier: GELA); BNLI-EORTC-20012 (Other Identifier: BNLI); GELCAB-EORTC-20012 (Other Identifier: GELCAB); NORDICLG-EORTC-20012 (Other Identifier: NLG); CAN-NCIC-EORTC-20012 (Other Identifier: NCIC CTG); ALLG-HD04 (Other Identifier: ALLG); 2004-001558-10 (EudraCT Number)