A Phase III Group-Wide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease

Trial Information

A Phase III Group-Wide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease

OBJECTIVES:

- Compare response-based therapy with doxorubicin, bleomycin, vincristine, etoposide,
prednisone, and cyclophosphamide with or without dexamethasone, etoposide, cytarabine,
cisplatin, and/or radiotherapy in children with intermediate-risk Hodgkin's lymphoma.

- Determine whether radiotherapy can be eliminated from this regimen based upon early and
complete response to multiagent chemotherapy in these patients.

- Determine whether the addition of dexamethasone, etoposide, cytarabine, cisplatin, and
filgrastim (G-CSF) improves outcome in those patients with a slow early response to
standard chemotherapy.

- Compare the frequency and severity of late effects of this therapy, including thyroid
dysfunction, infertility, cardiotoxicity, pulmonary toxicity, and second malignant
neoplasms, in patients treated with these regimens.

- Correlate results from biology and late effects studies with response to therapy,
event-free survival, and overall survival in these patients.

OUTLINE: This is a randomized, multicenter study.

- Initial chemotherapy (ABVE-PC): Patients receive doxorubicin IV over 10-30 minutes on
days 1-2, bleomycin IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on
days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily
on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim
(G-CSF) SC beginning on day 4 and continuing until blood counts recover (G-CSF is held
on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive
disease.

At the end of initial chemotherapy, patients undergo evaluation for response. Patients with
less than 60% disease reduction are considered to have slow early response (SER). Patients
with 60% or more disease reduction are considered to have rapid early response (RER).

- RER: Patients with RER receive 2 additional courses of ABVE-PC chemotherapy. After the
additional course, patients with less than a complete response undergo radiotherapy 5
days a week. Patients with a complete response are randomized to receive either
radiotherapy or no further treatment.

- SER: Patients with SER are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3
hours, and cytarabine IV over 3 hours on days 1-2 and cisplatin IV over 6 hours on
day 1. Patients also receive G-CSF SC beginning on day 3 and continuing until
blood counts recover. Treatment repeats every 21 days for 2 courses in the absence
of disease progression or unacceptable toxicity. After these 2 courses, patients
then receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo
radiotherapy.

- Arm II: Patients receive 2 additional courses of ABVE-PC chemotherapy. Patients
then undergo radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5-5.5
years.