Clinical Drug Experience Knowledgebase

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

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.)