Trial Information

A Randomized Trial Of BEAM Plus PBSCT Versus Single Agent High-Dose Therapy Followed By BEAM Plus PBSCT In Patients With Relapsed Hodgkin's Disease

OBJECTIVES:

- Compare the efficacy of induction chemotherapy followed by combination chemotherapy and
autologous peripheral blood stem cell transplantation with or without high-dose
sequential chemotherapy in terms of freedom from treatment failure in patients with
relapsed Hodgkin's lymphoma.

- Compare the toxicity of these regimens in these patients.

- Compare the complete remission/unconfirmed complete remission rate at 3 months,
relapse-free survival, and overall survival of patients treated with these regimens.

- Compare the frequency of severe toxic effects and secondary neoplasia in patients
treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center, type of relapse (early first relapse [remission duration 3-12 months]
vs late first relapse [remission duration more than 12 months] vs second relapse without
prior high-dose chemotherapy salvage [remission duration after salvage at least 3 months]),
disease status at relapse (stage I or II vs stage III or IV), age (18 to 49 vs 50 to 60),
and response after 2 courses of study induction chemotherapy (complete remission vs partial
remission vs no change).

All patients receive induction chemotherapy comprising dexamethasone IV over 30 minutes on
days 1-4 and 15-18, cisplatin IV continuously over 24 hours on days 1 and 15, cytarabine IV
over 3 hours every 12 hours on days 2 and 16, and filgrastim (G-CSF) subcutaneously (SC)
once daily on days 5-12 and days 19-26. Patients with complete remission (CR), unconfirmed
CR, partial remission, or no change are randomized to one of two treatment arms.

- Arm I: Patients receive BEAM chemotherapy comprising carmustine IV over 30 minutes and
melphalan IV over 30 minutes on day 37 and etoposide IV over 30 minutes every 12 hours
and cytarabine IV over 30 minutes every 12 hours on days 37-40. Patients also receive
G-CSF SC twice daily beginning on day 41 and continuing until blood counts recover.
Autologous peripheral blood stem cells (PBSCs) are reinfused on day 42.

- Arm II: Patients receive high-dose cyclophosphamide IV over 8 hours on day 37,
high-dose methotrexate IV over 6 hours and high-dose vincristine IV on day 51, and
high-dose etoposide IV over 8 hours on days 58-61. Patients then receive BEAM
chemotherapy comprising carmustine IV over 30 minutes and melphalan IV over 30 minutes
on day 80 and etoposide IV over 30 minutes every 12 hours and cytarabine IV over 30
minutes every 12 hours on days 80-83. Patients also receive G-CSF SC once on days 38
and 62 and twice daily beginning on day 84 and continuing until blood counts recover.
Autologous PBSCs are reinfused on day 85.

Patients with residual lymphoma at 100 days after completion of BEAM chemotherapy may
receive radiotherapy.

Patients are followed at 100 days after PBSC transplantation, every 3 months for 2 years,
every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A minimum of 220 patients (110 per treatment arm) will be accrued for
this study within 5 years.