Brentuximab Vedotin, Bendamustine, and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Inclusion Criteria:

CD30 detectable B lineage relapsed refractory NHL including the following histologies:

Aggressive lymphomas: diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, grey zone lymphomas, high grade B cell lymphomas, and transformed indolent lymphomas

Indolent lymphoma: follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma; indolent lymphoma patients eligible for this trial should have high tumor burden and high risk disease, as defined by:

The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
Intermediate or high risk by Follicular Lymphoma International Prognostic Index (FLIPI) score or elevated lactose dehydrogenase (LDH)/ beta-2 microglobulin (B2M)
Subjects between 18 and 75 years old. Subjects older than 75 years old to be discussed with PI prior to subject consent; consensus between PI and treating physician is required.
Karnofsky performance status (KPS) >= 70%, Eastern Cooperative Oncology Group (ECOG) =< 2
At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
Patients must have received at least one but no more than 4 prior lines of systemic therapy
American Heart Association (AHA) class 1 without significant limitation of physical activity
Ejection fraction (EF) of at least >= 40% by multigated acquisition (MUGA) or echocardiography (ECHO)
Total bilirubin =< 1.5 mg/dl
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 2.5 times the upper limit of normal without evidence of active infectious hepatitis
Creatinine clearance >= 40 ml/min
Platelets > 75,000 cells/ul
Absolute neutrophil count (ANC) > 1,000 cells/ul
Ability to provide informed consent
Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) pregnancy test at screening; pregnancy testing is not required for: (a) women who have been post-menopausal for at least 2 years without menses; or (b) women who are surgically sterile (e.g. by means of hysterectomy, tubal ligation, etc.)
Males and females of childbearing potential must be able and willing to use an effective contraceptive method during treatment and for three months after completing treatment

Exclusion Criteria:

Active infections (bacterial, fungal, or viral)
Evidence of sanctuary site involvement by disease, e.g., central nervous system, ocular, testicular involvement
Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
Recent chemotherapy within 3 weeks of screening
Major surgery within 4 weeks of screening
Diagnosed or treated for malignancy other than NHL for which patient will be treated, except: malignancy treated with curative intent and with no known active disease present for >= 3 years before subject registration; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease
History of stroke or intracranial hemorrhage within 6 months prior to registration
Requires anticoagulation with warfarin or equivalent vitamin K antagonists
Requires treatment with strong cytochrome (CYP3A4/5) inhibitors
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
Women who are pregnant or breastfeeding
Prior use of brentuximab vedotin
Prior use of bendamustine for indolent lymphoma allowed if > 2 years, CR to bendamustine and well tolerated with no residual > grade 1 toxicity; no prior use of bendamustine for aggressive lymphoma allowed
Prior allogeneic transplant
Patients with Child-Pugh B or C hepatic impairment