Ofatumumab In Older Patients With Untreated Low Or Intermediate Risk Indolent B-Cell Lymphomas

Inclusion Criteria: * Stage II, III, or IV follicular or marginal zone B-cell CD20+ lymphomas not previously treated with systemic therapy * Low/intermediate risk grade 1 or 2 follicular NHL or marginal zone lymphoma defined by 2004 Follicular Lymphoma International Prognostic Index (FLIPI) scores * Measurable disease as assessed by 2 dimensional measurement by CT and/or by bone marrow histopathology. * Age ≥ 70 years at time of informed consent * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Life expectancy of at least 3 months * Documented negative serologic testing for human immunodeficiency virus (HIV) * Documented negative serologic testing for Hepatitis B (HB); this is defined as negative for HBsAg; * If negative for HBsAg but HBcAb positive (regardless of HBsAb status), an hepatitis B virus (HBV) DNA test will be performed and must be negative for eligibility. Those with negative HBV DNA may be included but must undergo HBV DNA PCR testing every 2 months (see Time and Events table). Prophylactic antiviral therapy may be initiated at the discretion of the investigator in these patients. * Adequate bone marrow function (without transfusion support within four weeks of screening) as demonstrated by: * Hemoglobin ≥ 8 g/dL * Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 * Platelet count ≥ 50,000/mm3 * Adequate hepatic and renal function as demonstrated by: * Aspartate aminotransferase (AST/ALT) ≤ 2.5 × upper limit of normal (ULN) * Total serum bilirubin ≤ 1.5 × ULN * Alkaline phosphatase ≤ 2.5 × ULN * Serum creatinine ≤ 1.5 × ULN * If sexually active male with female partner of reproductive capability, has agreed to use a medically accepted form of contraception from time of enrollment to completion of initial follow-up study visit. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method, or total abstinence. * Signed an institutional review board (IRB)-approved informed consent document for this protocol Exclusion Criteria: * Prior therapies for lymphoma except involved field radiation therapy * Prior anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to first infusion of ofatumumab for any reason * Evidence of transformation to aggressive lymphoma * More than 10 x 109/L circulating CD20+ lymphoma cells * History of previous allergic reactions to compounds of similar biological or chemical composition as ofatumumab * Medical or other condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective * Other past or current malignancies with the exception of: * Patients who have been free of malignancy for at least 5 years * Completely resected, non-melanoma skin cancer * Successfully treated in situ carcinoma * Patients who have current active hepatic or biliary disease (with exception Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) * Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to first infusion of ofatumumab, whichever is longer, or currently participating in any other interventional clinical study * Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. * History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to first infusion of ofatumumab, congestive heart failure (NYHA III-IV), and arrhythmia (unless controlled by therapy), with the exception of extra systoles or minor conduction abnormalities. * Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. * Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the patient will be excluded.