Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma
- Conditions
- Lymphoma
- Registration Number
- NCT00005584
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy with radiation therapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is most effective in treating Hodgkin's lymphoma.
PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy with or without radiation therapy in treating patients who have Hodgkin's lymphoma.
- Detailed Description
OBJECTIVES:
* Compare the late toxicity of 6 courses of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by involved-field radiotherapy (IF-RT) (36 Gy) vs IF-RT (20 Gy), vs no IF-RT (closed to accrual as of 6/2002) in patients with supradiaphragmatic Hodgkin's lymphoma, favorable prognosis, and complete remission (CR) or CR unconfirmed after completion of chemotherapy. (Favorable prognosis group \[group 1\] closed to accrual as of 4/28/04.)
* Compare 6 courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) vs 4 courses of ABVD vs 4 courses of cyclophosphamide, doxorubicin, vincristine, bleomycin, etoposide, procarbazine, and prednisone (BEACOPP) followed by IF-RT, with respect to overall survival and late treatment-related toxicity, in patients with supradiaphragmatic Hodgkin's lymphoma and unfavorable prognosis. (Unfavorable prognosis group \[group 2\] closed to accrual as of 9/2002.) (Favorable prognosis group \[group 1\] closed to accrual as of 4/28/04.)
* Maintain the failure-free survival and relapse-free survival rates that were reached in the previous EORTC studies (H5 to H8), with a reduction in acute and delayed side effects of the treatment, in particular that of severe late radiotherapy and chemotherapy-related toxicity.
* Compare the quality of life, overall survival, treatment quality control, and duration of treatment in patients with favorable (closed to accrual as of 4/28/04) or unfavorable (closed to accrual as of 9/2002) prognoses treated with these regimens.
* Determine the efficacy of conservative therapy comprised of observation until disease progression (DP) and administration of IF-RT at the time of DP in patients with lymphocyte-predominant Hodgkin's lymphoma, nodular subtype (nodular paragranuloma).
OUTLINE: This is a randomized, multicenter study.
Patients with classical Hodgkin's lymphoma are assigned to 1 of 2 randomized groups. (Group 2 \[unfavorable prognosis\] closed to accrual as of 9/2002.) (Group 1 \[favorable prognosis\] closed to accrual as of 4/28/04.) Patients with lymphocyte-predominant Hodgkin's lymphoma are assigned to the nonrandomized group.
Randomized groups
* Patients are stratified by prognosis (favorable vs unfavorable). Patients are assigned to 1 of 2 treatment groups based on prognosis. (Group 2 \[unfavorable prognosis\] closed to accrual as of 9/2002.) (Group 1 \[favorable prognosis\] closed to accrual as of 4/28/04.)
* Group 1 (favorable prognosis) (closed to accrual as of 4/28/04): Patients receive epirubicin IV over 5 minutes, bleomycin intramuscularly (IM) (or IV if necessary), and vinblastine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 3 weeks for 6 courses. Patients are then assigned to 1 of 3 involved-field radiotherapy (IF-RT) groups based on response to chemotherapy:
* Group A (complete remission (CR) or CR unconfirmed \[CRu\]) Patients are randomized to 1 of 3 radiotherapy arms. (Arm III closed to accrual as of 6/2002.)
* Arm I (36 Gy): Patients undergo IF-RT 5 days a week for 3.5 weeks.
* Arm II (20 Gy): Patients undergo IF-RT 5 days a week for 2 weeks.
* Arm III (closed to accrual as of 6/2002): Patients undergo no IF-RT.
* Group B (partial remission \[PR\]): Patients undergo IF-RT 5 days a week for 3.5 weeks and boost radiotherapy.
* Group C (stable disease or disease progression \[DP\]): Patients receive no IF-RT and are taken off study.
* Group 2 (unfavorable prognosis) (closed to accrual as of 9/2002): Patients are randomized to 1 of 3 treatment arms.
* Arm I: Patients receive doxorubicin IV over 5 minutes, bleomycin IM (or IV if necessary), vinblastine IV, and dacarbazine IV over 5-10 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses.
* Arm II: Patients receive chemotherapy as in arm I. Treatment repeats every 4 weeks for 4 courses.
* Arm III: Patients receive cyclophosphamide IV and doxorubicin IV over 5 minutes on day 1, vincristine IV and bleomycin IM (or IV if necessary) on day 8, etoposide IV over a minimum of 30 minutes on days 1-3, oral procarbazine on days 1-7, and oral prednisone on days 1-14. Treatment repeats every 3 weeks for 4 courses.
Patients on all arms who achieve CR or CRu undergo IF-RT 5 days a week for 3 weeks. Patients who achieve PR undergo IF-RT 5 days a week for 3.5 weeks and boost radiotherapy.
* Groups 1 and 2 (group 2 closed to accrual as of 9/2002) (group 1 closed to accrual as of 4/28/04): IF-RT begins within 3-4 weeks after completion of the last course of chemotherapy.
Nonrandomized group
* Patients with completely resected stage I disease undergo observation until DP and undergo IF-RT after documentation of DP. Patients with stage II or incompletely resected stage I disease undergo IF-RT immediately.
Quality of life is assessed before starting study therapy, immediately after completion of study, and then annually for 10 years.
Patients are followed at 2, 4, 6, 9, and 12 months; every 4 months for 1 year; every 6 months for 3 years; and then annually thereafter.
PROJECTED ACCRUAL: A total of 903 patients (group 1) will be accrued for this study within 7.7 years. A total of 723 patients (group 2) will be accrued for this study within 3.8 years. (Group 2 \[unfavorable prognosis\] closed to accrual as of 9/2002.) (Group 1 \[favorable prognosis\] closed to accrual as of 4/28/04.)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1649
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Relapse-free rate 5 years with events defined as lack of CR/CRu at the end of treatment or relapse
- Secondary Outcome Measures
Name Time Method Failure Free Survival Till withdrawal criteria met Relapse Free Survival Till withdrawal criteria met Overall Survival Till withdrawal criteria met
Trial Locations
- Locations (121)
Sint Antonius Ziekenhuis
🇳🇱Nieuwegein, Netherlands
Centre Hospitalier Universitaire Vaudois
🇨ðŸ‡Lausanne, Switzerland
Leyenburg Ziekenhuis
🇳🇱's-Gravenhage, Netherlands
Institut Bergonie
🇫🇷Bordeaux, France
Hopital de Saint Germain-en-Laye
🇫🇷Saint Germain-en-Laye, France
Centre Hospitalier Universitaire Brugmann
🇧🇪Brussels, Belgium
Centre Hospital General Robert Ballanger
🇫🇷Aulnay Sous Bois, France
Centre Hospitalier de la Cote Basque
🇫🇷Bayonne, France
Hopital Saint Antoine
🇫🇷Paris, France
Hopital Pasteur
🇫🇷Nice, France
CHU de Caen
🇫🇷Caen, France
Clinique Gui de Chauliac
🇫🇷Montpellier, France
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Centre Hospitalier d'Annecy
🇫🇷Annecy, France
Centre Hospitalier Annemasse Bonneville
🇫🇷Ambilly, France
Hopital Notre-Dame de Bon Secours
🇫🇷Metz, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hotel Dieu de Paris
🇫🇷Paris, France
Hopital Rene Dubos
🇫🇷Pontoise, France
Centre Hospitalier Lens
🇫🇷Lens, France
Centre Hospitalier General
🇫🇷Lons le Saunier, France
Hopital Haut Leveque
🇫🇷Pessac, France
Centre Hospitalier Intercommunal de Poissy
🇫🇷Poissy, France
Hopital de la Croix Rouge Francaise des Peupliers
🇫🇷Paris, France
Polyclinique De Courlancy
🇫🇷Reims, France
Meander Medisch Centrum
🇳🇱Amersfoort, Netherlands
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
University Medical Center Nijmegen
🇳🇱Nijmegen, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Maasland Hospital
🇳🇱Sittard, Netherlands
Academisch Ziekenhuis Utrecht
🇳🇱Utrecht, Netherlands
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
🇵🇱Warsaw, Poland
Institute of Oncology, Ljubljana
🇸🇮Ljubljana, Slovenia
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Academisch Ziekenhuis Groningen
🇳🇱Groningen, Netherlands
Instituto Portugues de Oncologia Centro do Porto, SA
🇵🇹Porto, Portugal
National Cancer Institute - Bratislava
🇸🇰Bratislava, Slovakia
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hopital de Beziers
🇫🇷Beziers, France
Hopital Saint Andre
🇫🇷Bordeaux, France
CMC Bligny
🇫🇷Briis Sous Forges, France
Centre Hospitalier Regional de Chambery
🇫🇷Chambery, France
Hopital Louis Pasteur
🇫🇷Colmar, France
Centre Hospital Universitaire Hop Huriez
🇫🇷Lille, France
Centre Hospitalier Regional et Universitaire de Lille
🇫🇷Lille, France
Centre Hospital Regional Universitaire de Limoges
🇫🇷Limoges, France
Institut J. Paoli and I. Calmettes
🇫🇷Marseille, France
Institut Curie - Section Medicale
🇫🇷Paris, France
Hopital Lariboisiere
🇫🇷Paris, France
Hopital Saint-Louis
🇫🇷Paris, France
CHU Pitie-Salpetriere
🇫🇷Paris, France
CHG Roanne
🇫🇷Roanne, France
Hopital Duffaut
🇫🇷Avignon, France
Sint Augustinus Ziekenhuis
🇧🇪Antwerpen, Belgium
A.Z. St. Jan
🇧🇪Brugge, Belgium
C.H.U. Saint-Pierre
🇧🇪Brussels, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Clinique Universitaire De Mont-Godinne
🇧🇪Mont-Godinne Yvoir, Belgium
CHR de Besancon - Hopital Jean Minjoz
🇫🇷Besancon, France
C.H. Bourg En Bresse
🇫🇷Bourg En Bresse, France
Centre Regional Francois Baclesse
🇫🇷Caen, France
Centre d'Oncologie et de Radiotherapie de Chaumont le Bois
🇫🇷Chaumont, France
Hopital Fontenoy
🇫🇷Chartres, France
Hopital Antoine Beclere
🇫🇷Clamart, France
Hopital d'Instruction des Armees Percy
🇫🇷Clamart, France
Hopital Beaujon
🇫🇷Clichy, France
Centre Hospitalier Sud Francilien - Site Corbeil
🇫🇷Corbeil, France
Centre Hospitalier Compiegne
🇫🇷Compiegne, France
Centre Hospitalier Universitaire Henri Mondor
🇫🇷Creteil, France
Hopital Du Bocage
🇫🇷Dijon, France
Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
🇫🇷Dijon, France
Institut Prive de Cancerologie
🇫🇷Grenoble, France
Centre Hospitalier
🇫🇷Juvisy sur Orge, France
Hopital Andre Mignot
🇫🇷Le Chesnay, France
Centre Hospitalier Universitaire de Bicetre
🇫🇷Le Kremlin Bicetre, France
C.H.G. Du Havre - Hopital J. Monod
🇫🇷Le Havre, France
Clinique Victor Hugo
🇫🇷Le Mans, France
Clinique Saint Jean
🇫🇷Lyon, France
Centre Leon Berard
🇫🇷Lyon, France
Hopital Edouard Herriot
🇫🇷Lyon, France
Centre Hospitalier de Meaux
🇫🇷Meaux, France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
🇫🇷Montpellier, France
Intercommunal Hospital
🇫🇷Montfermeil, France
Centre Hospitalier de Mulhouse
🇫🇷Mulhouse, France
C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau
🇫🇷Nimes, France
Hopital Cochin
🇫🇷Paris, France
Hopital Necker
🇫🇷Paris, France
C.H.G. De Pau
🇫🇷Pau, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
Centre Henri Becquerel
🇫🇷Rouen, France
Centre Rene Huguenin
🇫🇷Saint Cloud, France
Centre Hospitalier Regional de Purpan
🇫🇷Toulouse, France
Centre Hospitalier Valence
🇫🇷Valence, France
C.H.U. Saint Etienne Hospital Nord
🇫🇷Saint Etienne, France
Centre Medico-Chirurgical Foch
🇫🇷Suresnes, France
Centre Hospitalier de Valenciennes
🇫🇷Valenciennes, France
Centre Alexis Vautrin
🇫🇷Vandoeuvre-les-Nancy, France
Hopital Paul Brousse
🇫🇷Villejuif, France
CHU de Nancy - Hopitaux de Brabois
🇫🇷Vandoeuvre-Les-Nancy, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centro di Riferimento Oncologico - Aviano
🇮🇹Aviano, Italy
Ospedale Sta. Maria Delle Croci
🇮🇹Ravenna, Italy
Ospedale S. Giovanni A.S. Dipartimente di Oncologia di Turin
🇮🇹Turin, Italy
Comprehensive Cancer Center Amsterdam
🇳🇱Amsterdam, Netherlands
Groot Ziekengasthuis 's-Hertogenbosch
🇳🇱's-Hertogenbosch, Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
🇳🇱Amsterdam, Netherlands
Medisch Centrum Alkmaar
🇳🇱Alkmaar, Netherlands
Streekziekenhuizen Gooi-Noord
🇳🇱Blaricum, Netherlands
Amphia Ziekenhuis - locatie Molengracht
🇳🇱Breda, Netherlands
Atrium Medisch Centrum - Brunssum
🇳🇱Brunssum, Netherlands
Reinier de Graaf Group
🇳🇱Delft, Netherlands
Atrium Medical Centre
🇳🇱Heerlen, Netherlands
Radiotherapeutisch Instituut
🇳🇱Leeuwarden, Netherlands
Diaconessenhuis Leiden
🇳🇱Leiden, Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Hopital Cantonal Universitaire de Geneve
🇨ðŸ‡Geneva, Switzerland