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.

Inclusion Criteria:

- Histologically confirmed mantle cell or follicular lymphoma

- Relapsed or refractory disease

- ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, 2 or 3

Exclusion Criteria:

- Pre-existing sensory or motor peripheral neuropathy

- No active or untreated CNS (Central Nervous System) lymphoma

- History of severe, life-threatening hypersensitivity or infusion reactions prior
rituximab treatment.