Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	15 to 70	Other	EORTC-20982 FRE-FNCLCC-98014, GELA-H9, NCT00005584

Objectives

1. 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.)
2. 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.)
3. 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.
4. 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.
5. 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).

Entry Criteria

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

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

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

Expected Enrollment

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.)

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.

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 (11): A-814, 2005.

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 Hodgkin's lymphoma (HL) . [Abstract] J Clin Oncol 23 (Suppl 16): A-6505, 561s, 2005.

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). [Abstract] Eur J Haematol 75 (Suppl 65): A-E11a, 40, 2004.

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 (20982) in 808 patients. [Abstract] Eur J Haematol 73 (Supp 65): A-E12, 40, 2004.

van der Kaaij MA, Heutte N, Le Stang N, et al.: 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 25 (19): 2825-32, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Jose Thomas, MD, Study coordinator		Ph: 32-16-347670 Email: jose.thomas@uz.kuleuven.ac.be
H. Eghbali, MD, Study coordinator		Ph: 33-55-633-3214 Email: eghbali@bergonie.org
E.M. Noordijk, MD, Study coordinator		Ph: 31-71-526-3057 Email: e.m.noordijk@lumc.nl
Christophe Ferme, Study coordinator		Ph: 33-1-6926-3000

Groupe d'Etudes de Lymphomes de L'Adulte

Christian Gisselbrecht, MD, Study coordinator		Ph: 33-1-4249-9296

Federation Nationale des Centres de Lutte Contre le Cancer

Thierry Philip, MD, Study coordinator		Ph: 33-4-78-78-26-45 Email: philip@lyon.fnclcc.fr

Registry Information
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
Trial Start Date		1998-10-15
Registered in ClinicalTrials.gov		NCT00005584
Date Submitted to PDQ		2000-02-11
Information Last Verified		2001-07-25