The purpose of this study is to determine safety and tolerability of combination therapy of SGN-40 with gemcitabine and rituximab for the treatment of lymphoma. This study is also intended to estimate how well your disease responds to this treatment.

Inclusion Criteria:

• Have a histologic diagnosis of DLBCL, including transformed histology and follicular grade 3 disease.
• Must have at least one site of biopsy-proven disease demonstrating both of the following: bidimensional measurable disease with the longest axis >= 1.5cm by radiographic imaging or positive FDG-PET scan at baseline.
• Patients with DLBCL and who have either relapsed, refractory, or progressive disease following salvage therapy, OR relapsed, refractory, or progressive disease following initial therapy and be medically unfit to receive aggressive therapy.
• Either fresh or archived tumor specimen must be available.

Exclusion Criteria:

• Documented history within 6 months of registration of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms.
• Patients who have received allogeneic stem cell transplant.
• Patients with evidence of another invasive primary malignancy within the past three years other than non-melanoma skin cancer, cervical carcinoma in situ, in situ carcinoma of the breast, or fully resected prostate cancer with normal PSA within 8 weeks of registration.
• Patients with any active systemic viral, bacterial, or fungal infection requiring intravenous anti-infectives within 4 weeks prior to first dose of study drug.
• Patients with a history or clinical evidence of leptomeningeal or central nervous system (CNS) lymphoma.