Single Agent Ofatumumab Vs. Single Agent Rituximab in Indolent B-Cell Non Hodgkin Lymphoma Relapsed After Rituximab-Containing Therapy

Inclusion Criteria: 1. Indolent NHL subtypes defined according to World Health Organization guidelines: 1. Follicular lymphoma Grades 1, 2, 3 A 2. Small lymphocytic lymphoma (SLL) 3. Marginal zone lymphoma 4. Lymphoplasmacytic lymphoma 2. Rituximab-sensitive iNHL, defined as a partial or complete response to their last prior treatment with rituximab or a rituximab-containing regimen lasting at least 6 months following completion of rituximab treatment. 3. Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 RRCML criteria, which requires therapy. 4. Radiographically measurable disease, defined as: 2 or more clearly demarcated lesions/nodes with a long axis \>1.5 cm and short axis ≥1.0cm. OR 1 clearly demarcated lesion/node with a long axis \>2.0 cm and short axis ≥1.0cm. 5. ECOG Performance Status of 0, 1, or 2. 6. Age ≥18 years. 7. Life expectancy of at least 6 months in the opinion of the investigator. 8. The patient or their legally acceptable representative must be capable of giving written informed consent prior to performing any study-specific tests or procedures. 9. All prior treatment related non-hematologic toxicities (with the exception of alopecia) must have resolved to CTCAE (Version 4.0) ≤ Grade 2 at the time of randomization. 10. One or more of the following indications for treatment: 1. Cytopenias 2. One or more of the following lymphoma-related symptoms: * Night sweats without signs of infection * Unintentional weight loss (10% within the previous 6 months) * Recurrent, unexplained fever of greater than 100.5F (38C) without signs of infection * Fatigue which interferes with the patient's quality of life 3. Progressive or massive lymphadenopathy OR 4. Progressive or massive organomegaly French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Exclusion Criteria: 1. Previous treatment with ofatumumab. 2. Previous anti-CD20 radioimmunotherapy (RIT) or non-rituximab anti-CD20 therapy (such as obinutuzumab) within 6 months prior to randomization. Patients who have received previous anti-CD20 RIT or non-rituximab anti-CD20 therapy (such as obinutuzumab) must have attained a partial or complete response lasting at least 6 months, and must have recovered from any hematologic or other toxicity. 3. Previous autologous stem cell transplantation within 6 months prior to randomization. 4. Previous allogeneic stem cell transplantation. 5. Previous anti-lymphoma monoclonal antibody therapy (excluding anti-CD20 therapy and anti-CD20 RIT), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months prior to randomization. 6. Current or previous participation in the treatment phase of another interventional clinical study within 4 weeks prior to randomization. Patients may continue in the follow-up phase of another interventional clinical study, but may not have undergone any treatment on the other study within 4 weeks prior to randomization. 7. Current or previous other malignancy within 2 years prior to randomization. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ, are eligible. 8. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known HIV disease. All HIV-positive patients are excluded from this study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy. Prophylactic antiviral and/or antibacterial antibiotics to prevent recurrence of previous infections are permitted. 9. Clinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, and uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmias such as atrial fibrillation whose cardiac disease is well controlled on a stable medical regimen are eligible. 10. Other significant concurrent, uncontrolled medical conditions including, but not limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which, in the investigator's opinion, will impact study participation. 11. Screening laboratory values: 1. Neutrophils \< 1.5 x 10\^9/L (unless due to iNHL involvement of the bone marrow) 2. Platelets \< 50 x 10\^9/L (unless due to iNHL involvement of the bone marrow) 3. ALT or AST \> 3 x ULN 4. Alkaline phosphatase \> 1.5 x ULN (unless due to lymphoma or a non-malignant, non-hepatic cause such as Paget's disease) 5. Total bilirubin \> 1.5 x ULN (unless due to lymphoma or isolated, predominantly indirect hyperbilirubinemia due to Gilbert's syndrome) 12. Known or suspected inability to fully comply with study protocol 13. Because the effects of ofatumumab on fetuses and nursing infants are not known, the following are ineligible for study entry: 1. Lactating women. 2. Women with a positive pregnancy test at study entry. 3. Men with partners of childbearing potential and women of childbearing potential who are not willing to use adequate contraception from study entry through one year following last treatment dose. (Adequate contraception is defined as abstinence, oral hormonal birth control, hormonal birth control injections, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilization if male partner is the sole partner for a female subject. The double barrier method can be used in regions where considered acceptable and adequate, defined as condom or occlusive cap plus spermicidal agent). 14. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones). 15. 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 HB DNA test will be performed and if positive the subject will be excluded.