Trial Information

Protocol H8 for a Prospective Controlled Trial in Clinical Stage I-II Supradiaphragmatic Hodgkin's Disease. Evaluation of Treatment Efficacy and (Long Term) Toxicity in Three Different Prognostic Subgroups [H8 Trial]

OBJECTIVES:

- Evaluate the efficacy of mantle field radiotherapy, in terms of overall survival, in
patients with previously untreated stage I or II Hodgkin's lymphoma (HL) with a very
favorable prognosis.

- Compare late treatment-related toxicity in patients with stage I or II HL with a
favorable prognosis treated with standard subtotal nodal radiotherapy vs a combination
of 3 courses of mechlorethamine, vincristine, procarbazine hydrochloride,
prednisone/doxorubicin hydrochloride, bleomycin, and vinblastine (MOPP/ABV) followed by
involved field radiotherapy.

- Compare overall survival and late treatment-related toxicity in patients with stage I
or II HL with an unfavorable prognosis treated with 6 courses of MOPP/ABV followed by
involved field radiotherapy vs 4 courses of MOPP/ABV followed by involved field
radiotherapy vs subtotal nodal radiotherapy.

- Maintain the failure-free survival rate that was reached in previous studies, with a
reduction of the acute side effects of the treatment, particularly severe late
toxicity.

OUTLINE: This is a randomized, controlled, prospective, multicenter study. Patients are
stratified according to prognosis (favorable vs unfavorable vs very favorable).

- Stratum 1 (very favorable prognosis): Patients undergo mantle field radiotherapy 5 days
a week for at least 4 weeks.

- Stratum 2 (favorable prognosis): Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo subtotal nodal radiotherapy 5 days a week for at least 4
weeks.

- Arm II: Patients receive mechlorethamine IV and vincristine IV on day 1; oral
procarbazine hydrochloride on days 1-7; oral prednisone on days 1-14; and
doxorubicin hydrochloride IV, bleomycin intramuscularly (IM) or IV, and
vinblastine IV on day 8. Treatment repeats every 4 weeks for 3 courses in the
absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks after
completion of chemotherapy, patients undergo involved field radiotherapy 5 days a
week for at least 4 weeks.

- Stratum 3 (unfavorable prognosis): Patients are randomized to 1 of 3 treatment arms.

- Arm I: Patients receive mechlorethamine IV and vincristine IV on day 1; oral
procarbazine hydrochloride on days 1-7; oral prednisone on days 1-14; and
doxorubicin hydrochloride IV, bleomycin IM or IV, and vinblastine IV on day 8.
Treatment repeats every 4 weeks for 6 courses in the absence of disease
progression or unacceptable toxicity. Beginning 3-4 weeks after completion of
chemotherapy, patients undergo involved field radiotherapy 5 days a week for at
least 4 weeks.

- Arm II: Patients receive chemotherapy as in arm I. Treatment repeats every 4 weeks
for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients then undergo involved field radiotherapy as in arm I.

- Arm III: Patients receive chemotherapy as in arm I. Treatment repeats every 4
weeks for 4 courses in the absence of disease progression or unacceptable
toxicity. Beginning 3-4 weeks after completion of chemotherapy, patients undergo
subtotal nodal radiotherapy 5 days a week for at least 4 weeks.

Quality of life is assessed after completion of study treatment and then annually for 10
years.

After completion of study treatment, 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 1,158 patients will be accrued for this study.