Trial Information

Pilot Study for the Treatment of Children With Newly Diagnosed Advanced Stage Hodgkin's Disease: Upfront Dose Intensive Chemotherapy

OBJECTIVES: I. Determine the feasibility and toxicity of bleomycin, etoposide, doxorubicin,
cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) induction in pediatric
patients with previously untreated stage II, stage III, or stage IV Hodgkin's disease. II.
Determine rates of complete response and rapid early partial response (defined as greater
than 70% reduction in the size of a bulky mediastinal mass or nodal aggregate and a negative
gallium scan) in these patients treated with 4 courses of BEACOPP. III. Determine whether
thallium scans effectively measure response to therapy in these patients treated with this
regimen. IV. Evaluate the expression of markers of apoptosis in tumor samples from these
patients at diagnosis and at time of relapse, and correlate expression of these markers with
response to therapy and overall outcome. V. Determine the utility of seven molecular genetic
markers as surrogate markers of genotoxic damage caused by this regimen in these patients.
VI. Estimate the incidence of therapy related late effects, including second malignant
neoplasms, sterility, cardiac dysfunction, pulmonary restrictive disease, growth
abnormalities, and thyroid disease in these patients.

OUTLINE: Induction: On day 0, patients receive cyclophosphamide IV over 30 minutes,
doxorubicin IV over 15-30 minutes, etoposide IV over 1 hour, oral prednisone every 12 hours,
and oral procarbazine. On days 1 and 2, patients receive etoposide IV over 1 hour, oral
prednisone every 12 hours, and oral procarbazine. On days 3-6, patients receive oral
prednisone every 12 hours and oral procarbazine. On day 7, patients receive vincristine IV,
bleomycin IV over 5 minutes, and oral prednisone every 12 hours. On days 8-13, patients
receive oral prednisone every 12 hours. Beginning on day 8, patients receive filgrastim
(G-CSF) subcutaneously until absolute neutrophil counts recover. Treatment repeats every 3
weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Consolidation therapy begins on week 12 or when blood counts recover. Consolidation for
rapid early responders (patients with complete response (CR) or rapid early partial response
(PR-1) to induction therapy): Females - Patients receive vincristine IV, cyclophosphamide IV
over 30 minutes, oral prednisone every 12 hours, and oral procarbazine on day 0. On days
1-6, patients receive oral prednisone every 12 hours and oral procarbazine. On day 7,
patients receive vinblastine IV, bleomycin IV over 5 minutes, doxorubicin IV over 15-30
minutes, and oral prednisone every 12 hours. On days 8-13, patients receive oral prednisone
every 12 hours. Treatment repeats every 28 days for a total of 4 courses in the absence of
disease progression or unacceptable toxicity. Males - Patients receive doxorubicin IV over
15-30 minutes, bleomycin IV over 5 minutes, vinblastine IV, and dacarbazine IV on days 0 and
14. Treatment repeats every 28 days for a total of 2 courses in the absence of disease
progression or unacceptable toxicity. Beginning 3 weeks after completion of chemotherapy,
male patients with CR or PR-1 receive radiotherapy 5 days per week to areas of initial
disease involvement (total duration of radiotherapy is dependent on initial extent of
disease). Consolidation for slow early responders: Patients with slow partial response
(PR-2) or stable disease (SD) after 4 courses of induction therapy receive 4 additional
courses of induction therapy in the absence of disease progression or unacceptable toxicity.
Beginning on day 8, patients receive G-CSF subcutaneously until blood counts recover.
Patients should be off G-CSF for more than 24 hours prior to the next course of
chemotherapy. Beginning 3 weeks after completion of chemotherapy, male and female patients
with PR-2 or SD receive radiotherapy 5 days per week to areas of initial disease involvement
(total duration of radiotherapy is dependent on initial extent of disease). Patients are
followed every 3 months for 2 years, every 6 months for 1 year, annually for 2 years and
then at years 10 and 20.

PROJECTED ACCRUAL: Approximately 25-50 patients will be accrued for this study.