Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Prospective Controlled Trial in Clinical Stages I-II Supradiaphragmatic Hodgkin's Disease: Evaluation of Treatment Efficacy, (Long Term) Toxicity and Quality of Life in Two Different Prognostic Subgroups

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00005584
• Other study ID #: EORTC-20982
• Secondary ID: FRE-FNCLCC-98014
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 1998

Study information

• Verified date: February 2024
• 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. 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1649
• Est. primary completion date: May 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 70 Years

Eligibility

DISEASE CHARACTERISTICS:

• Randomized groups: Histologically proven previously untreated stage I or II supradiaphragmatic Hodgkin's lymphoma

• No prior staging laparotomy

• Favorable (closed to accrual as of 4/28/04) 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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• bleomycin sulfate

Drug:
• ABVD regimen

• BEACOPP regimen

• epirubicin hydrochloride

• prednisone

• vinblastine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Sint Augustinus Ziekenhuis	Antwerpen
Belgium	A.Z. St. Jan	Brugge
Belgium	C.H.U. Saint-Pierre	Brussels
Belgium	Centre Hospitalier Universitaire Brugmann	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir
Belgium	Clinique Saint-Pierre	Ottignies
France	Centre Hospitalier Annemasse Bonneville	Ambilly
France	Centre Hospitalier d'Annecy	Annecy
France	Centre Hospital General Robert Ballanger	Aulnay Sous Bois
France	Hopital Duffaut	Avignon
France	Centre Hospitalier de la Cote Basque	Bayonne
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Hopital de Beziers	Beziers
France	Hopital Saint Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	C.H. Bourg En Bresse	Bourg En Bresse
France	CMC Bligny	Briis Sous Forges
France	Centre Regional Francois Baclesse	Caen
France	CHU de Caen	Caen
France	Centre Hospitalier Regional de Chambery	Chambery
France	Hopital Fontenoy	Chartres
France	Centre d'Oncologie et de Radiotherapie de Chaumont le Bois	Chaumont
France	Hopital Antoine Beclere	Clamart
France	Hopital d'Instruction des Armees Percy	Clamart
France	Hopital Beaujon	Clichy
France	Hopital Louis Pasteur	Colmar
France	Centre Hospitalier Compiegne	Compiegne
France	Centre Hospitalier Sud Francilien - Site Corbeil	Corbeil
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	Centre de Lutte Contre le Cancer, Georges-Francois Leclerc	Dijon
France	Hopital Du Bocage	Dijon
France	Institut Prive de Cancerologie	Grenoble
France	Centre Hospitalier	Juvisy sur Orge
France	Hopital Andre Mignot	Le Chesnay
France	C.H.G. Du Havre - Hopital J. Monod	Le Havre
France	Centre Hospitalier Universitaire de Bicetre	Le Kremlin Bicetre
France	Clinique Victor Hugo	Le Mans
France	Centre Hospitalier Lens	Lens
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	Centre Hospitalier General	Lons le Saunier
France	Centre Leon Berard	Lyon
France	Clinique Saint Jean	Lyon
France	Hopital Edouard Herriot	Lyon
France	Institut J. Paoli and I. Calmettes	Marseille
France	Centre Hospitalier de Meaux	Meaux
France	Hopital Notre-Dame de Bon Secours	Metz
France	Intercommunal Hospital	Montfermeil
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Clinique Gui de Chauliac	Montpellier
France	Centre Hospitalier de Mulhouse	Mulhouse
France	Centre Antoine Lacassagne	Nice
France	Hopital Pasteur	Nice
France	C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau	Nimes
France	CHU Pitie-Salpetriere	Paris
France	Hopital Cochin	Paris
France	Hopital de la Croix Rouge Francaise des Peupliers	Paris
France	Hopital Lariboisiere	Paris
France	Hopital Necker	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Saint-Louis	Paris
France	Hotel Dieu de Paris	Paris
France	Institut Curie - Section Medicale	Paris
France	C.H.G. De Pau	Pau
France	Hopital Haut Leveque	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Centre Hospitalier Intercommunal de Poissy	Poissy
France	Hopital Rene Dubos	Pontoise
France	Polyclinique De Courlancy	Reims
France	CHG Roanne	Roanne
France	Centre Henri Becquerel	Rouen
France	Centre Rene Huguenin	Saint Cloud
France	C.H.U. Saint Etienne Hospital Nord	Saint Etienne
France	Hopital de Saint Germain-en-Laye	Saint Germain-en-Laye
France	Centre Medico-Chirurgical Foch	Suresnes
France	Centre Hospitalier Regional de Purpan	Toulouse
France	Centre Hospitalier Valence	Valence
France	Centre Hospitalier de Valenciennes	Valenciennes
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	CHU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy
France	Hopital Paul Brousse	Villejuif
France	Institut Gustave Roussy	Villejuif
Italy	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
Netherlands	Leyenburg Ziekenhuis	's-Gravenhage
Netherlands	Groot Ziekengasthuis 's-Hertogenbosch	's-Hertogenbosch
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Comprehensive Cancer Center Amsterdam	Amsterdam
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Streekziekenhuizen Gooi-Noord	Blaricum
Netherlands	Amphia Ziekenhuis - locatie Molengracht	Breda
Netherlands	Atrium Medisch Centrum - Brunssum	Brunssum
Netherlands	Reinier de Graaf Group	Delft
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Netherlands	Atrium Medical Centre	Heerlen
Netherlands	Radiotherapeutisch Instituut	Leeuwarden
Netherlands	Diaconessenhuis Leiden	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam
Netherlands	Maasland Hospital	Sittard
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Portugal	Instituto Portugues de Oncologia Centro do Porto, SA	Porto
Slovakia	National Cancer Institute - Bratislava	Bratislava
Slovenia	Institute of Oncology, Ljubljana	Ljubljana
Spain	Hospital Universitario 12 de Octubre	Madrid
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (3)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Lymphoma Study Association, UNICANCER

Countries where clinical trial is conducted

Belgium,  France,  Italy,  Netherlands,  Poland,  Portugal,  Slovakia,  Slovenia,  Spain,  Switzerland, 

References & Publications (8)

Eghbali H, Brice P, Creemers GY, et al.: Comparison of three radiation dose levels after EBVP regimen in favorable supradiaphragmatic clinical stages (CS) I-II Hodgkin's lymphoma (HL): preliminary results of the EORTC-GELA H9-F trial. [Abstract] Blood 106

Ferme C, Diviné M, Vranovsky A, et al.: Four ABVD and involved-field radiotherapy in unfavorable supradiaphragmatic clinical stages (CS) I-II Hodgkin's lymphoma (HL): preliminary results of the EORTC-GELA H9-U trial. [Abstract] Blood 106 (11): A-813, 2005

Girinsky T, Gargi T, Carrie C, et al.: Quality assurance program in the EORTC-GELA H9 randomized study results on 282 patients. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A77, S47, 2005.

Noordijk EM, Thomas J, Fermé C, et al.: First results of the EORTC-GELA H9 randomized trials: the H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgki

Thomas J, Ferme C, Noordijk EM, et al.: Six cycles of ABVD + IF-RT vs. four cycles of ABVD + IF-RT vs. four cycles of BEACOPP + IF-RT in unfavourable supradiaphragmatic clinical stages I-II Hodgkin's lymphoma: the EORTC-GELA H9-U randomized clinical trial

Thomas J, Ferme C, Noordijk EM, et al.: Six cycles of EBVP followed by 36 Gy involved-field irradiation vs. no irradiation in favourable supradiaphragmatic clinical stages I-II Hodgkin's lymphoma: the EORTC-GELA strategy in 771 patients (H9-F trial-20982)

van der Kaaij MA, Heutte N, Le Stang N, Raemaekers JM, Simons AH, Carde P, Noordijk EM, Ferme C, Thomas J, Eghbali H, Kluin-Nelemans HC, Henry-Amar M; European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group; Groupe d'Etude des Lymphomes de l'Adulte. Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Jul 1;25(19):2825-32. doi: 10.1200/JCO.2006.10.2020. Epub 2007 May 21. — View Citation

van der Kaaij MA, Heutte N, van Echten-Arends J, Raemaekers JM, Carde P, Noordijk EM, Ferme C, Thomas J, Eghbali H, Brice P, Bonmati C, Henry-Amar M, Kluin-Nelemans HC. Sperm quality before treatment in patients with early stage Hodgkin's lymphoma enrolled in EORTC-GELA Lymphoma Group trials. Haematologica. 2009 Dec;94(12):1691-7. doi: 10.3324/haematol.2009.009696. Epub 2009 Oct 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse-free rate	with events defined as lack of CR/CRu at the end of treatment or relapse	5 years
Secondary	Overall Survival		Till withdrawal criteria met
Secondary	Failure Free Survival		Till withdrawal criteria met
Secondary	Relapse Free Survival		Till withdrawal criteria met