Bevacizumab + CHOP-Rituximab in Untreated Mantle Cell Lymphoma

Bevacizumab administered at 15 mg/kg on day 1 of each of 6 cycles

Rituximab administered 375 mg/m2 on day 3 of each of 6 cycles (with usual premedications)

Standard CHOP chemotherapy administered on day 3 every 21 days (full dose) for 6 cycles of
treatment

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 mantle cell Non-Hodgkin's Lymphoma with
characteristic immunophenotypic profile: CD5(+), CD19(+) or CD20(+), cyclin D1(+),
CD23(-) and CD10(-)

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

- Laboratory parameters (unless considered by investigator to be due to lymphoma):

Absolute neutrophil count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Hemoglobin > 7
gm/dL Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN

- Patient has at least one tumor mass > 1.5 cm in one dimension

- Available tumor tissue for correlative studies (rebiopsy to be performed if needed)

- Patient is > 18 years old

- Patient has KPS > 50%

- Patient has signed IRB-approved informed consent

- Patient agrees to use birth control for duration of study

Exclusion Criteria:

- Known central nervous system (CNS) involvement by lymphoma

- Known hepatitis infection

- Known HIV positivity

- Known history of renal disease with proteinuria; urine protein:creatinine ratio ³1.0
at screening

- Uncontrolled hypertension: blood pressure of >150/100 mmHg at screening

- Unstable angina

- History of myocardial infarction within 6 months

- History of stroke within 6 months

- Clinically significant peripheral vascular disease

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- Patient has ejection fraction < 50%

- Patient is taking coumadin, or has known history of thrombosis within last 6 months

- Evidence of bleeding diathesis or coagulopathy

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1, anticipation of need for major surgical procedure during the course of
the study

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 1

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months prior to Day 1

- Serious, non-healing wound, ulcer, or bone fracture

- Concomitant malignancies or previous malignancies within the last five years, with the
exception of adequately treated basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix.

- Patient is pregnant or nursing

- Patient is receiving other investigational drugs