Clinical trial NCT00049595: Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma
Official title: BEACOPP (4 Cycles Escalated + 4 Cycles Baseline) Versus ABVD (8 Cycles) In Stage III & IV Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: adult lymphocyte depletion Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Lymphoma Trials Office
name: Lymphoma Study Association
name: Grup per l'Estudi dels Limfomes de Catalunya i Balears
name: NCIC Clinical Trials Group
name: Australasian Leukaemia and Lymphoma Group
name: Nordic Lymphoma Group
First posted: 2003-01-27
Enrollment: 552
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Event-free survival
timeFrame: from randomization to early discontinuation of protocol treatment, no CR/CRu after 8 cycles, relapse, progression or death
Secondary outcomes:
measure: Complete response as assessed by Cheson criteria adapted to Hodgkin's lymphoma
timeFrame: from randomization till end of treatment
measure: Disease-free survival in patients with complete response
timeFrame: from the day of first documentation of CR to the day of relapse
measure: Overall survival
timeFrame: from the date of randomization to the date of death
measure: 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
timeFrame: from one week prior to randomization till 10 years after end of treatment or death
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Kingswood
country: Australia
facility: Nepean Cancer Care Centre at Nepean Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital - Melbourne
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire Brugmann
city: Charleroi
country: Belgium
facility: Centre Hospitalier Notre Dame - Reine Fabiola
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Ghent
country: Belgium
facility: Algemeen Ziekenhuis Sint Lucas
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Roeselare
country: Belgium
facility: H. Hartziekenhuis - Roeselaere
city: Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Winnipeg
country: Canada
facility: Centre Hospitalier De Dunkerque - CHD
state: Manitoba
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: St. Johns
country: Canada
facility: Doctor H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Edmond Odette Cancer Centre at Sunnybrook
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre at Windsor Regional Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hotel Dieu Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint-Sacrement - Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Prague
country: Czechia
facility: Thomayer's University Hospital
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Bayonne
country: France
facility: Centre Hospitalier de la Cote Basque
city: Besancon
country: France
facility: Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Boucher
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Bourg En Bresse
country: France
facility: C.H. Bourg En Bresse
city: Caen
country: France
facility: CHU de Caen
city: Caen
country: France
facility: Polyclinique Du Parc
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chambery
country: France
facility: Centre Hospitalier Regional de Chambery
city: Clamart
country: France
facility: Hopital d'Instruction des Armees Percy
city: Clamart
country: France
facility: Hopital Antoine Beclere
city: Clermont-Ferrand
country: France
facility: CHR Clermont Ferrand, Hotel Dieu
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Corbeil
country: France
facility: Centre Hospitalier Sud Francilien - Site Corbeil
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dijon
country: France
facility: Hopital Du Bocage
city: Grenoble
country: France
facility: Institut Prive de Cancerologie
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Lille
country: France
facility: Hopital Saint Antoine Lille
city: Lille
country: France
facility: Centre Hospitalier Regional et Universitaire de Lille
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Hopital Edouard Herriot - Lyon
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Melun
country: France
facility: Centre Hospitalier Marc Jacquet
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: Hopital de l'Archet CHU de Nice
city: Paris
country: France
facility: Hotel Dieu de Paris
city: Paris
country: France
facility: Institut Curie Hopital
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Necker
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Pontoise
country: France
facility: Hopital Rene Dubos
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Hopital Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Etienne
country: France
facility: CHU Sainte-Etienne - Hopital Bellevue
city: Saint Germain-en-Laye
country: France
facility: Hopital de Saint Germain-en-Laye
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Suresnes
country: France
facility: Hopital Foch
city: Valence
country: France
facility: Centre Hospitalier Valence
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
city: Vandoeuvre-Les-Nancy
country: France
facility: CHU de Nancy - Hopitaux de Brabois
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: 's-Gravenhage
country: Netherlands
facility: HagaZiekenhuis - Locatie Leyenburg
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Delft
country: Netherlands
facility: Reinier de Graaf Group - Delft
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Heerlen
country: Netherlands
facility: Atrium Medical Centre - Heerlen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Roermond
country: Netherlands
facility: Saint Laurentius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Gothenburg (Goteborg)
country: Sweden
facility: Sahlgrenska University Hospital
city: Linkoping
country: Sweden
facility: University Hospital of Linkoping
city: Lund
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital - Huddinge
city: Umea
country: Sweden
facility: Umea Universitet
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Birmingham
country: United Kingdom
facility: Raigmore Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
state: England
city: Kettering
country: United Kingdom
facility: Kettering General Hosptial
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Patrice P. Carde, MD
role: STUDY_CHAIR
affiliation: Middlesex Hospital
name: David C. Linch
role: STUDY_CHAIR
affiliation: Centre Hospitalier Universitaire Henri Mondor
name: Marine Divine, MD
role: STUDY_CHAIR
affiliation: Hospital de la Santa Cruz i Sant Pau
name: Anna Sureda
role: STUDY_CHAIR
affiliation: Margaret and Charles Juravinski Cancer Centre
name: Ralph M. Meyer, MD, FRCPC
role: STUDY_CHAIR
affiliation: St Vincent's Hospital
name: David Ma, MD
role: STUDY_CHAIR
affiliation: Princess Alexandra Hospital
name: Devinder Gill, MD
role: STUDY_CHAIR
affiliation: Uppsala University Hospital
name: Bengt Glimelius, MD
role: STUDY_CHAIR
References:
citation: 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.