Phase I/II Trial of VELCADE + CHOP-Rituximab in Untreated DLCBL or Mantle Cell NHL

Standard CHOP chemotherapy administered every 21 days (full dose) for six cycles

Rituximab administered (375 mg/m2) day 1 of each cycle (with usual premedications)

VELCADE is administered prior to rituximab and CHOP on day 1 of each cycle. The dose of
VELCADE will be determined by the following dose escalation schedule:

Once completed six cycles of therapy (~18 weeks), patients will be evaluated every 3 months
for the first year post treatment, then every 6 months until disease progression or death for
years 2 through 5 post treatment. Patients who have disease progression will be contacted
every 6 months until death to assess for survival status.

Inclusion Criteria:

- Histologically confirmed diagnosis of diffuse large B cell or mantle cell
Non-Hodgkin's Lymphoma with characteristic immunophenotypic profiles. For mantle cell:
CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-).

- Patient has not received any prior anti-cancer therapy for lymphoma

- Tumor tissue confirmed to express the CD20 antigen

- Available frozen tumor tissue(rebiopsy if needed)

- Patient has measurable disease as defined by a tumor mass > 1.5 cm

- Patient has Stage II, III, or IV disease

- Age > 18 years

- Absolute granulocyte count > 1000 cells/mm3

- Platelet count > 50,000 cells/mm3

- Creatinine < 2.0 x ULN

- Total bilirubin < 2.0 x ULN

Exclusion Criteria:

- Known central nervous system (CNS) involvement by lymphoma

- Known HIV disease

- Patient is pregnant or nursing

- Patient has had major surgery within the last 3 weeks

- Patient is receiving other investigational drugs

- Known peripheral neuropathy > Grade 2