Trial Information

A Phase II Study of Velcade (Bortezomib, PS-341) and Rituximab in Relapsed/Refractory Mantle Cell and Follicular Non-Hodgkin's Lymphoma

Rationale: Previous studies testing bortezomib and rituximab separately indicate these
agents have some efficacy against mantle cell lymphoma (MCL). Bortezomib is a targeted
cancer drug that blocks proteasomes. The proteasome is an enzyme complex existing in all
cells that influences proteins controlling cellular processes. By blocking the proteasome,
bortezomib disrupts biologic pathways such as those related to the growth and survival of
cancer cells. Rituximab is a monoclonal antibody that attaches to a protein called the CD20
antigen that is found almost exclusively on the surface of B-cells with leukemia. Once
rituximab attaches to the protein, the immune system activates to kill the malignant
B-cells. The current study combines bortezomib and rituximab in patients with relapsed or
refractory MCL.

Purpose: This study will evaluate the safety and efficacy of bortezomib and rituximab in
patients with relapsed or refractory MCL. Blood, molecular, and tumor analysis will be
conducted to provide researchers with information about areas such as rituximab resistance,
the effects of bortezomib on cells associated with immune function, and protein alterations
related to the cellular growth and death of MCL. In addition, the role of maintenance
therapy and timing of administration in MCL will be assessed.

Treatment: Patients in this study will receive bortezomib and rituximab. Both drugs will be
administered through intravenous infusions. There are two treatment periods in this study.
The first is considered induction therapy where patients will receive bortezomib and
rituximab intermittently over an eighteen week period. Lower dosages of rituximab will be
given to patients at the beginning of the study to ensure no severe toxicity occurs. Those
patients without disease growth after the eighteen weeks of treatments will continue with
maintenance therapy. During this time period, patients will be given bortezomib and
rituximab for up to one year and a half. Several tests and exams will be conducted
throughout the study to closely monitor patients. Treatments will be discontinued due to
disease growth or unacceptable side effects.