Brentuximab Vedotin in CD30 Positive Epstein Barr Virus (EBV) Positive DLBCL of Elderly

The main purpose of this study is to test if brentuximab vedotin has an effect on cancer in patients with a certain type of large B-Cell Lymphoma. The side effects (unwanted effects) of SGN-35 in patients with this certain type of large B-Cell Lymphoma will also be studied. It is not known if brentuximab vedotin is better or worse than other treatment that might be given.

Brentuximab vedotin is a type of drug called an antibody drug conjugate (ADC). ADCs usually have 2 parts; a part that targets cancer cells (the antibody) and a cell killing part (the chemotherapy). Antibodies are proteins that are part of the immune system. They can stick to and attack specific targets on cells. The antibody part of brentuximab vedotin sticks to a target called CD30. CD30 is an important molecule on some cancer cells (including non-Hodgkin lymphoma) and some normal cells of the immune system. The cell killing part of brentuximab vedotin is a chemotherapy called monomethyl auristatin E (MMAE). After the brentuximab vedotin attaches to the CD30 part of the cell, the MMAE enters the cell and kills it.

More than 350 people with cancer have already been given brentuximab vedotin in research studies. These research studies were done to test the safety of different doses of brentuximab vedotin and to find out if brentuximab vedotin is active against cancer.

Eligibility Criteria:
Inclusion Criteria:

* Confirmed diagnosis of CD30+EBV+DLBCLE (EDLBCLE). Diagnosis will be based on identification of diffuse large cell lymphoma (DLBCL) in biopsy specimens characterized by positivity in the malignant cell population of 2 principal markers:

  * CD30 by immunohistochemistry (IHC) and
  * Epstein-Barr virus (EBV) by EBER in situ hybridization (ISH)
* Histology slides and pathology material must be available at the site for each patient before enrollment in order to be sent to the Leading Institution of the study for central pathology review and pharmacodynamic studies.
* Patients must have progressive, relapsed or refractory disease after:

  * At least one prior systemic anti-lymphoma regimen (chemotherapy or immunotherapy)
  * Relapsed or failed autologous or allogeneic stem cell transplant.
* Understand and voluntarily sign an Institutional Review Board (IRB) approved informed consent form
* Must have at least one site of disease (index lesion) measurable in two dimensions by computed tomography (CT)
* At least 4 weeks since the last chemotherapy, radiation therapy, immunotherapy or any investigational non-immunotherapy products with clinical evidence of recovery from any toxicity associated with such treatment
* Must meet the following criteria within 4 days before the first dose of study drug:

  * Neutrophils ≥1,000/ul
  * Hemoglobin ≥ 8 g/dL
  * Platelets≥ 50.0x10\^9 /L
  * Total bilirubin ≤ 1.5 x upper normal limit, or ≤ 5 x upper normal limit if documented hepatic involvement with lymphoma or history of Gilbert's Syndrome
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper normal limit (≤ 5 x upper normal limit if documented hepatic involvement with lymphoma)
  * Calculated creatinine clearance ≥ 40 mL/min/1.73 m\^2 based on Cockcroft and Gault method
  * Prothrombin time (PT) or international normalization ratio (INR), and activated partial thromboplastin time (APTT) ≤ 1.5 x upper limit of normal (ULN) unless patient is receiving anticoagulants. If patient is on anticoagulation therapy, levels should be within therapeutic range.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Negative pregnancy test for women of childbearing potential
* Recovered (≤ Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy

Exclusion Criteria:

* Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug: Myocardial infarction and the New York Heart Association (NYHA) Class III or IV heart failure.
* History of another primary malignancy not in remission for at least 3 years; except adequately treated patients with completely resected in situ carcinoma, such as nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear
* Known active cerebral/meningeal involvement with lymphoma. Asymptomatic patients with previously treated and resolved central nervous system (CNS) lymphoma involvement are permitted.
* Prior administration of Brentuximab vedotin
* Corticosteroid monotherapy for lymphoma within 2 weeks of the first dose of study drug
* Radioimmunotherapy administration within 8 weeks before the first dose of study drug
* Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair the ability to receive or tolerate the planned treatment
* Known hypersensitivity to recombinant proteins, or any component contained in the drug formulation
* Female patients who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug