Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma

Inclusion Criteria

• All patients must have previously untreated Stage III, IV, or bulky Stage II diffuse large B-cell non-Hodgkin's lymphoma which is positive for CD20; a report providing confirmation of CD20 expression must be submitted
• Pathology Review: Adequate sections from the original diagnostic specimen must be available for submission for review by the SWOG Lymphoma Pathology Laboratory; an adequate biopsy requires sufficient tissue to establish the architecture and a REAL or WHO histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies may be adequate; whereas, needle aspirations or cytologies are not adequate
• Specimens for analysis of angiogenic markers must be submitted to the University of Arizona
• All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all nonmeasurable disease assessed within 42 days prior to registration
• Patients must have a unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
• Patients must have a CT scan of the chest/abdomen and pelvis performed within 28 days prior to registration
• Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration
• Patients may not have a previous diagnosis of indolent lymphoma (histologic transformation or mixed histologies with an indolent or nodular component are ineligible)
• Patients must not have received prior chemotherapy, radiation, or antibody-based therapy for lymphoma
• Patients must have a Zubrod performance status of 0 - 2
• Serum LDH must be measured within 28 days prior to registration
• Patients must have a cardiac ejection fraction >= 45% by MUGA scan or a 2-d ECHO with no significant abnormalities within 42 days prior to registration
• Absolute neutrophil count > 1, 000/mcL obtained within 28 days prior to registration
• Platelet count > 100, 000/mcL obtained within 28 days prior to registration
• Serum creatinine = +1 or urine protein:creatinine ratio >= 1.0, a 24 hour urine protein should be obtained and the level < 1gm/24 hours to be eligible
• Patients must not have a history of hypersensitivity reaction to products containing Polysorbate 20 (Tween 20), Chinese hamster ovary cell products, or recombinant human antibodies
• Patients known to be HIV-positive, or who have a history of solid organ transplantation are ineligible due to the concern over immunosuppression associated with B-cell depletion; patients at high risk of Hepatitis B virus infection should be screened before initiation of rituximab
• Patients must not have uncontrolled hypertension
• Patients with a history of prior myocardial infarction, unstable angina, stroke, or arterial thrombosis within 6 months are ineligible
• Patients with clinically significant peripheral vascular disease, a serious or non-healing wound, ulcer, or bone fracture, or a bleeding diathesis/coagulopathy are ineligible
• Patients with a history of venous thrombosis requiring full-dose anticoagulation or currently receiving anticoagulation therapy may be eligible provided that the following criteria are met:
• The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on a stable dose of LMW heparin
• The patient must not have bleeding or pathological conditions that carry a high risk of bleeding (e.g. tumor involving major vessels, known varices)
• Patients who have had a major surgical procedure or traumatic injury within 28 days prior to registration or anticipation of major surgical procedure during the course of therapy are ineligible
• Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months are ineligible
• Patients requiring cont