Trial Information

A Randomised Phase III Study On The Effect Of The Chimeric Anti-CD20 Monoclonal Antibody (Mabthera) During Sequential Chemotherapy Followed By Autologous Stem Cell Transplantation In Patients With Relapse B-Cell Non-Hodgkin Lymphoma(HOVON 44 STUDY)

OBJECTIVES:

- Compare the partial and complete response rates in patients with relapsed, CD20
positive, aggressive B-cell non-Hodgkin's lymphoma treated with dexamethasone,
cisplatin, and cytarabine in combination with etoposide, ifosfamide, and methotrexate
with or without rituximab followed by carmustine, etoposide, cytarabine, melphalan, and
autologous peripheral blood stem cell transplantation (APBSCT).

- Compare the effect of APBSCT with or without rituximab on the overall and event-free
survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center. Patients are randomized to one of two treatment arms.

- Arm I: Patients receive DHAP induction chemotherapy comprising dexamethasone orally or
IV on days 1-4, cisplatin IV continuously over 24 hours on day 1, and cytarabine IV
over 3 hours every 12 hours on day 2. Beginning 3-4 weeks after DHAP, patients receive
VIM induction chemotherapy comprising etoposide IV over 2 hours on days 1, 3, and 5;
ifosfamide IV over 1 hour on days 1-5; and methotrexate IV on days 1 and 5. Beginning
3-4 weeks after VIM, patients with partial or complete response after DHAP and VIM
receive a second course of DHAP (patients with progressive or unresponsive disease
after DHAP but responsive disease after VIM receive a second course of VIM) followed by
filgrastim (G-CSF) subcutaneously beginning on day 10 and continuing until a target
number of cells are collected.

- Arm II: Patients receive induction chemotherapy and G-CSF as in arm I. At 1 day after
the last dose of each chemotherapy course, patients also receive rituximab IV once for
a maximum of 3 courses.

At 4-5 weeks after the completion of the last induction chemotherapy course, responsive
patients in both arms receive BEAM conditioning chemotherapy comprising carmustine IV over
60 minutes on day -6, etoposide IV over 60 minutes and cytarabine IV over 30 minutes on days
-5 to -2, and melphalan IV over 15 minutes on day -1. Patients undergo autologous peripheral
blood stem cell transplantation on day 0. After transplantation, patients in partial
remission may undergo radiotherapy to nodal sites with residual tumor mass.

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

PROJECTED ACCRUAL: A total of 296-340 patients (148-170 per treatment arm) will be accrued
for this study within 4-5 years.