PS-341 Alone and PS-341 Plus EPOCH Chemotherapy to Treat Non-Hodgkin's Lymphoma

Inclusion Criteria

• •ELIGIBILITY CRITERIA:
• •Large B-cell lymphoma (subtypes: DLBCL (diffuse large B-cell lymphoma);
• •mediastinal (thymic) large B-cell lymphoma;
• •transformed large B-cell lymphoma;
• •follicular grade IIIB large B-cell lymphoma;
• •intravascular large B-cell lymphoma).
• •Confirmed pathological diagnosis at the treating institution.
• •Prior anthracycline-based treatment.
• •Age greater than or equal to 18 years.
• •Available tumor tissue for biopsy.
• •Eastern Cooperative Oncology Group (ECOG) performance 2 or better.
• •Major organ function: Absolute neutrophil count (ANC) greater than or equal to 1,000/microliters,
• •Platelet greater than or equal to 50,000/microliters,
• •creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 60 cc/min;
• •serum glutamic pyruvic transaminase (SGPT) less than 5 x upper limit of normal;
• •bilirubin less than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80 percent unconjugated; unless impairment due to organ involvement by lymphoma.
• •Informed consent and willingness to use contraception by both men and women.
• •Not pregnant or nursing because of an unknown potential for teratogenic or abortifacient effects.
• •Both male and female patients must be willing to use adequate contraception.
• •Human immunodeficiency virus (HIV) serology negative.
• •HIV positive patients receiving combination anti-retroviral therapy are excluded from the study because of positive pharmacokinetic interactions with PS-341 or the combination of PS-341 and EPOCH.
• •Additionally, the biology of HIV associated DLBCL's is often quite different from HIV negative disease due to involvement of Epstein Barr Virus (EBV).
• •Hepatitis B surface antigen negative.
• •No symptomatic cardiac disease or cardiac ejection fraction less than 40 percent (in patients receiving EPOCH).
• •No active central nervous system (CNS) lymphoma.
• •No systemic cytotoxic or experimental treatments within 4 weeks of treatment.