Inclusion Criteria:

• Patients must have a histological diagnosis of B cell non-Hodgkin's lymphoma, including diffuse large B-cell, mantle cell, follicular, small lymphocytic, and marginal zone lymphoma by the World Health Organization criteria.
• Patients must have an archived paraffin or fresh tumor specimen available for immunohistologic evaluation of CD40, CD20, & CD79a.
• Patients must have relapsed lymphoma and must have failed frontline chemotherapy.
• Patients who have not received autologous stem cell transplant must have refused or be ineligible for it.
• Patients must have completed radiotherapy, chemotherapy, and/or treatment with investigational anti-cancer agents 4 weeks prior to registration. Patients must have completed any monoclonal antibody treatment, including rituximab, 6 months prior to registration.
• Patients must have completed autologous bone marrow transplant 4 months prior to registration.
• Patient must have at least one site of measurable disease defined by unidimensional lesion ≥ 2 cm by conventional CT scan.
• Patients must have an ECOG performance status ≤ 2 and a life expectancy > 3 months.

• Patients must have the following required baseline laboratory data:

  • Platelet count ≥ 75,000/mm3,
  • Hemoglobin ≥ 9.0 g/dL,
  • Absolute neutrophil count ≥ 1,250/mm3,
  • ALT/AST ≤ 2.5 times ULN,
  • Total bilirubin ≤ 1.5 times ULN,
  • Creatinine < 1.5 mg/dL,
• Females of childbearing potential must have a negative serum β-hCG pregnancy test result within 3 days prior to the first dose of SGN-40 and must agree to use an effective contraceptive method during the course of the study and for 6 months following the last dose of study drug.
• If a deep venous thrombosis or other vascular even has required medical or surgical intervention in the past year, patients must either be on stable dose of anticoagulant therapy for at least 3 weeks or have completed anticoagulant therapy at least 3 months prior to registration with radiographic confirmation that thrombosis is resolved.
• Patients must be at least 18 years of age.
• Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution.

Exclusion Criteria:

• Patients with history or clinical evidence of leptomeningeal or central nervous system (CNS) lymphoma.
• Patients with a documented history within 6 months of registration of a cerebral vascular event, myocardial infarction, deep venous thrombosis or other vascular event that has required medical or surgical intervention. Patients must have completed anticoagulant therapy at least 3 months prior to registration. Prophylactic anticoagulant therapy for indwelling catheters is acceptable.
• Patients who have received an allogeneic stem cell transplant.
• Patients who have had major surgery within 4 weeks prior to registration.
• Patients with a known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
• Patients with a history of another primary malignancy that has not been in remission for at least 5 years (non-melanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear are exempt from the five year limit).
• Patients with any active systemic viral, bacterial, or fungal infection within four weeks prior to registration.
• Patients with known positivity for HIV, hepatitis B or hepatitis C infection.
• Patients with a history of significant chronic or recurrent infections requiring treatment.
• Patients with a history of migraines or severe headaches requiring medical therapy within 12 months of enrollment.
• Patients on systemic steroids who have not been on a stable daily dose (not exceeding 10 mg prednisone or equivalent) during 4 weeks prior to the first dose of SGN 40.
• Patients who are pregnant or breastfeeding.
• Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment.
• Patients with dementia or altered mental status that would preclude the understanding and/or rendering of informed consent.