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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00049595
• Other study ID #: EORTC-20012
• Secondary ID: EORTC-20012GELA-
• Status: Completed
• Phase: Phase 3
• Start date: August 2002

Study information

• Verified date: November 2023
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 552
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Biological:
• bleomycin sulfate

• filgrastim

• pegfilgrastim

Drug:
• ABVD regimen

• BEACOPP regimen

• cyclophosphamide

• dacarbazine

• doxorubicin hydrochloride

• etoposide

• prednisone

• procarbazine hydrochloride

• vinblastine sulfate

• vincristine sulfate

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	St. Vincent's Hospital - Melbourne	Fitzroy	Victoria
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Nepean Cancer Care Centre at Nepean Hospital	Kingswood	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp
Belgium	AZ Sint-Jan	Brugge
Belgium	Centre Hospitalier Universitaire Brugmann	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Algemeen Ziekenhuis Sint Lucas	Ghent
Belgium	Hopital de Jolimont	Haine Saint Paul
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Centre Hospitalier Regional de la Citadelle	Liege
Belgium	H. Hartziekenhuis - Roeselaere	Roeselare
Belgium	Clinique Universitaire De Mont-Godinne	Yvoir
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	CHUM - Hotel Dieu Hospital	Montreal	Quebec
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Hopital du Saint-Sacrement - Quebec	Quebec City	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Doctor H. Bliss Murphy Cancer Centre	St. Johns	Newfoundland and Labrador
Canada	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario
Canada	Edmond Odette Cancer Centre at Sunnybrook	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Windsor Regional Cancer Centre at Windsor Regional Hospital	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Canada	Centre Hospitalier De Dunkerque - CHD	Winnipeg	Manitoba
Croatia	University Hospital Rebro	Zagreb
Czechia	Thomayer's University Hospital	Prague
France	Centre Hospitalier d'Annecy	Annecy
France	Centre Hospitalier de la Cote Basque	Bayonne
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Institut Bergonie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Boucher
France	C.H. Bourg En Bresse	Bourg En Bresse
France	Centre Regional Francois Baclesse	Caen
France	CHU de Caen	Caen
France	Polyclinique Du Parc	Caen
France	Centre Hospitalier Regional de Chambery	Chambery
France	Hopital Antoine Beclere	Clamart
France	Hopital d'Instruction des Armees Percy	Clamart
France	CHR Clermont Ferrand, Hotel Dieu	Clermont-Ferrand
France	Hopital Louis Pasteur	Colmar
France	Centre Hospitalier Sud Francilien - Site Corbeil	Corbeil
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	Hopital Du Bocage	Dijon
France	Institut Prive de Cancerologie	Grenoble
France	Hopital Andre Mignot	Le Chesnay
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Hopital Saint Antoine Lille	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Centre Leon Berard	Lyon
France	Hopital Edouard Herriot - Lyon	Lyon
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	Centre Hospitalier de Meaux	Meaux
France	Centre Hospitalier Marc Jacquet	Melun
France	Hopital Notre-Dame de Bon Secours	Metz
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre Hospitalier de Mulhouse	Mulhouse
France	Centre Antoine Lacassagne	Nice
France	Hopital de l'Archet CHU de Nice	Nice
France	CHU Pitie-Salpetriere	Paris
France	Hopital Cochin	Paris
France	Hopital Necker	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Saint-Louis	Paris
France	Hotel Dieu de Paris	Paris
France	Institut Curie Hopital	Paris
France	Hopital Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Hopital Rene Dubos	Pontoise
France	Institut Jean Godinot	Reims
France	Hopital Sud	Rennes
France	Centre Henri Becquerel	Rouen
France	Centre Rene Huguenin	Saint Cloud
France	CHU Sainte-Etienne - Hopital Bellevue	Saint Etienne
France	Hopital de Saint Germain-en-Laye	Saint Germain-en-Laye
France	Hopital Universitaire Hautepierre	Strasbourg
France	Hopital Foch	Suresnes
France	Centre Hospitalier Valence	Valence
France	Centre Hospitalier de Valenciennes	Valenciennes
France	CHU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy
France	Hopital Paul Brousse	Villejuif
France	Institut Gustave Roussy	Villejuif
Hungary	National Institute of Oncology	Budapest
Netherlands	HagaZiekenhuis - Locatie Leyenburg	's-Gravenhage
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Reinier de Graaf Group - Delft	Delft
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Atrium Medical Centre - Heerlen	Heerlen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	Saint Laurentius Ziekenhuis	Roermond
Netherlands	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
New Zealand	Auckland City Hospital	Auckland
New Zealand	Waikato Hospital	Hamilton
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw	Warsaw
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Cruz i Sant Pau	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Sweden	Sahlgrenska University Hospital	Gothenburg (Goteborg)
Sweden	University Hospital of Linkoping	Linkoping
Sweden	Lund University Hospital	Lund
Sweden	Karolinska University Hospital - Huddinge	Stockholm
Sweden	Umea Universitet	Umea
Sweden	Uppsala University Hospital	Uppsala
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Raigmore Hospital	Birmingham	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	Hull Royal Infirmary	Hull	England
United Kingdom	Kettering General Hosptial	Kettering	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Middlesex Hospital	London	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Staffordshire General Hospital	Stafford	England

Sponsors (7)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Australasian Leukaemia and Lymphoma Group, Grup per l'Estudi dels Limfomes de Catalunya i Balears, Lymphoma Study Association, Lymphoma Trials Office, NCIC Clinical Trials Group, Nordic Lymphoma Group

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Croatia,  Czechia,  France,  Hungary,  Netherlands,  New Zealand,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival		from randomization to early discontinuation of protocol treatment, no CR/CRu after 8 cycles, relapse, progression or death
Secondary	Complete response as assessed by Cheson criteria adapted to Hodgkin's lymphoma		from randomization till end of treatment
Secondary	Disease-free survival in patients with complete response		from the day of first documentation of CR to the day of relapse
Secondary	Overall survival		from the date of randomization to the date of death
Secondary	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