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 chemotherapyregimen is most effective in treating Hodgkin's lymphoma.

PURPOSE: Randomizedphase 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.

Condition	Treatment or Intervention	Phase
stage I adult Hodgkin's lymphoma stage II adult Hodgkin's lymphoma adult lymphocyte predominant Hodgkin's lymphoma	Drug: bleomycin  Drug: epirubicin  Drug: prednisone  Drug: vinblastine  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

Further Study Details: 

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.
• 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.)
• 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 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.) 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.)
• 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:
• 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.
• 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.
• 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, oralprocarbazine 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): 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.)

Ages Eligible for Study:  15 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Randomized groups: Histologically proven previously untreated stage I or II supradiaphragmatic Hodgkin's lymphoma
• No prior staging laparotomy
• Favorable or unfavorable (closed to accrual as of 9/2002) prognosis
• Nonrandomized group: Histologically proven lymphocyte predominant Hodgkin's lymphoma, nodular subtype (nodular paragranuloma)
• Stage I with complete or incomplete resection OR
• Stage II

PATIENT CHARACTERISTICS: Age:

• 15 to 70

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No severe cardiac disease that would interfere with normal life expectancy or study treatment

Pulmonary:

• No severe pulmonary disease that would interfere with normal life expectancy or study treatment

Other:

• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No severe neurologic or metabolic disease that would interfere with normal life expectancy or study treatment
• No psychologic, familial, socioeconomic, or geographic circumstances that would preclude proper staging or compliance
• HIV negative
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy for this malignancy

Chemotherapy

• No prior chemotherapy for this malignancy

Endocrine therapy

• No prior endocrine therapy for this malignancy

Radiotherapy

• No prior radiotherapy for this malignancy

Surgery

• No prior surgery for this malignancy

Belgium
      A.Z. St. Jan, Brugge,  8000,  Belgium
      C.H.U. Saint-Pierre, Brussels,  1000,  Belgium
      Centre Hospitalier Universitaire Brugmann, Brussels,  B 1020,  Belgium
      Clinique Saint-Pierre, Ottignies,  B-1340,  Belgium
      Clinique Universitaire De Mont-Godinne, Mont-Godinne Yvoir,  5530,  Belgium
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      Sint Augustinus Ziekenhuis, Antwerpen,  2610,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
France
      C.H. Bourg En Bresse, Bourg-en-Bresse,  01012,  France
      C.H.G. De Pau, Pau,  64046 Universite Cedex,  France
      C.H.G. Du Havre - Hopital J. Monod, Le Havre,  76083,  France
      C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau, Nimes,  30000,  France
      C.H.U. Saint Etienne Hospital Nord, Saint-Etienne,  42055,  France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre de Lutte Contre le Cancer, Georges-Francois Leclerc, Dijon,  21079,  France
      Centre d'Oncologie et de Radiotherapie de Chaumont le Bois, Chaumont,  52000,  France
      Centre Henri Becquerel, Rouen,  76038,  France
      Centre Hospital General Robert Ballanger, Aulnay-sous-Bois,  93602,  France
      Centre Hospital Regional Universitaire de Limoges, Limoges,  87042,  France
      Centre Hospital Universitaire Hop Huriez, Lille,  59037,  France
      Centre Hospitalier Annemasse Bonneville, Ambilly,  74100,  France
      Centre Hospitalier Compiegne, Compiegne,  60321,  France
      Centre Hospitalier d'Annecy, Annecy,  74011 Cedex,  France
      Centre Hospitalier de la Cote Basque, Bayonne,  64109,  France
      Centre Hospitalier de Meaux, Meaux,  77104,  France
      Centre Hospitalier de Mulhouse, Mulhouse,  68051,  France
      Centre Hospitalier de Valenciennes, Valenciennes,  59300,  France
      Centre Hospitalier General, Lons-le-Saunier,  39000,  France
      Centre Hospitalier Intercommunal de Poissy, Poissy,  78498,  France
      Centre Hospitalier Lens, Lens,  Cedex 62307,  France
      Centre Hospitalier Lyon Sud, Pierre-Benite,  69310,  France
      Centre Hospitalier Regional de Chambery, Chambery,  73011,  France
      Centre Hospitalier Regional de Purpan, Toulouse,  31059,  France
      Centre Hospitalier Regional et Universitaire de Lille, Lille,  59037,  France
      Centre Hospitalier Sud Francilien - Site Corbeil, Corbeil,  91100,  France
      Centre Hospitalier Universitaire de Bicetre, Le Kremlin-Bicetre,  94275,  France
      Centre Hospitalier Universitaire Henri Mondor, Creteil,  94010,  France
      Centre Hospitalier Valence, Valence,  26000,  France
      Centre Hospitalier, Juvisy-sur-Orge,  91260,  France
      Centre Leon Berard, Lyon,  69373,  France
      Centre Medico-Chirurgical Foch, Suresnes,  92151,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Regional Francois Baclesse, Caen,  14076,  France
      Centre Rene Huguenin, Saint Cloud,  92211,  France
      CHG Roanne, Roanne,  F-42300,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHU de Caen, Caen,  14033,  France
      CHU de Nancy - Hopitaux de Brabois, Vandoeuvre-les-Nancy,  54511,  France
      CHU Pitie-Salpetriere, Paris,  75651,  France
      Clinique Gui de Chauliac, Montpellier,  34295,  France
      Clinique Saint Jean, Lyon,  69008,  France
      Clinique Victor Hugo, Le Mans,  F-72000,  France
      CMC Bligny, Briis-sous-Forges,  91640,  France
      Hopital Andre Mignot, Le Chesnay,  78157,  France
      Hopital Antoine Beclere, Clamart,  92141,  France
      Hopital Beaujon, Clichy,  92110,  France
      Hopital Cochin, Paris,  75674,  France
      Hopital de Beziers, Beziers,  34500,  France
      Hopital de la Croix Rouge Francaise des Peupliers, Paris,  75013,  France
      Hopital de Saint Germain-en-Laye, Saint-Germain-en-Laye,  78104,  France
      Hopital d'Instruction des Armees Percy, Clamart,  92140,  France
      Hopital Du Bocage, Dijon,  21034,  France
      Hopital Duffaut, Avignon,  84902,  France
      Hopital Edouard Herriot, Lyon,  69437,  France
      Hopital Fontenoy, Chartres,  28018,  France
      Hopital Haut Leveque, Pessac,  33604,  France
      Hopital Lariboisiere, Paris,  75475,  France
      Hopital Louis Pasteur, Colmar,  68024,  France
      Hopital Necker, Paris,  75743,  France
      Hopital Notre-Dame de Bon Secours, Metz,  55038,  France
      Hopital Pasteur, Nice,  06002,  France
      Hopital Paul Brousse, Villejuif,  94804,  France
      Hopital Rene Dubos, Pontoise,  95300,  France
      Hopital Saint Andre, Bordeaux,  33075,  France
      Hopital Saint Antoine, Paris,  75012,  France
      Hopital Saint-Louis, Paris,  75475,  France
      Hotel Dieu de Paris, Paris,  75181,  France
      Institut Bergonie, Bordeaux,  33076,  France
      Institut Curie - Section Medicale, Paris,  75248,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
      Institut J. Paoli and I. Calmettes, Marseille,  13273,  France
      Institut Prive de Cancerologie, Grenoble,  38100,  France
      Intercommunal Hospital, Montfermeil,  93370,  France
      Polyclinique De Courlancy, Reims,  F-51100,  France
Italy
      Centro di Riferimento Oncologico - Aviano, Aviano,  33081,  Italy
      Ospedale S. Giovanni A.S. Dipartimente di Oncologia di Turin, Turin,  10123,  Italy
      Ospedale Sta. Maria Delle Croci, Ravenna,  48100,  Italy
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
      Academisch Ziekenhuis Utrecht, Utrecht,  3584 CX,  Netherlands
      Amphia Ziekenhuis - locatie Molengracht, Breda,  4818 CK,  Netherlands
      Atrium Medical Centre, HEERLEN,  6419 PC,  Netherlands
      Atrium Medisch Centrum - Brunssum, Brunssum,  6442 BE,  Netherlands
      Catharina Ziekenhuis, Eindhoven,  5602 ZA,  Netherlands
      Comprehensive Cancer Center Amsterdam, Amsterdam,  1006 CX,  Netherlands
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands
      Diaconessenhuis Leiden, Leiden,  2300 RD,  Netherlands
      Groot Ziekengasthuis 's-Hertogenbosch, 's-Hertogenbosch,  5211 NL,  Netherlands
      Leyenburg Ziekenhuis, 's-Gravenhage,  2545 CH,  Netherlands
      Maasland Hospital, Sittard,  6131 BK,  Netherlands
      Meander Medisch Centrum, Amersfoort,  3816 CP,  Netherlands
      Medisch Centrum Alkmaar, Alkmaar,  1815 JD,  Netherlands
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands
      Radiotherapeutisch Instituut, Leeuwarden,  8934 AD,  Netherlands
      Reinier de Graaf Group, Delft,  NL 2600 GA,  Netherlands
      Sint Antonius Ziekenhuis, Nieuwegein,  3435 CM,  Netherlands
      Streekziekenhuizen Gooi-Noord, Blaricum,  1261 AN,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland
Portugal
      Instituto Portugues de Oncologia Centro do Porto, SA, Porto,  4200,  Portugal
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia
Slovenia
      Institute of Oncology, Ljubljana, LJUBLJANA,  Sl-1000,  Slovenia
Spain
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
      Hopital Cantonal Universitaire de Geneve, Geneva,  CH-1211,  Switzerland

Study chairs or principal investigators

Jose Thomas, MD,  U.Z. Gasthuisberg   
H. Eghbali, MD,  Institut Bergonie   
E.M. Noordijk, MD,  Leiden University Medical Center   
Christophe Ferme,  CMC Bligny   
Christian Gisselbrecht, MD,  Hopital Saint-Louis   
Thierry O. Philip, MD,  Centre Leon Berard   

Study ID Numbers:  CDR0000067652; EORTC-20982; FRE-FNCLCC-98014; GELA-H9
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00005584
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08