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.