Ofatumumab is a drug that works by attaching to the CD20 molecule found on the surface of cancerous B cells, and then triggering the death of those cells. It is approved by the FDA for treatment of another B-cell cancer, chronic lymphocytic leukemia, and also has evidence of success in people who's B-cell lymphomas have relapsed after initial treatments. In this research study we are looking to see if ofatumumab is effective and safe in treating previously untreated B-cell NHL.

• Participants will receive ofatumumab once a week for 8 weeks by intravenous infusion (Days 1, 8, 15, 22, 29, 36, 43, and 50).
• Participants will be seen weekly during the 8 week treatment period and will have the following tests and procedures performed: Blood tests, performance status and physical examination.

Inclusion Criteria:

• Histologically confirmed indolent CD20+B-cell NHL of the following histologies: follicular lymphoma, grades 1-2; Marginal zone lymphoma (extranodal, nodal or splenic); small lymphocytic lymphoma; low-grade B-cell lymphoma not otherwise specified with CD20+ expression
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater CT scan or MRI
• No previous chemotherapy, antibody therapy or radioimmunotherapy for this disease. Patients previously treated with external beam radiation alone are eligible
• 18 years of age or older
• Life expectancy of greater than 3 months
• ECOG Performance status of 0, 1 or 2
• Organ function as described in the protocol
• Women of child-bearing potential and men must agree so use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Prior chemotherapy, antibody therapy or radioimmunotherapy for lymphoma
• Participants may not be receiving any other investigational agent
• Participants with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab
• Prior exposure to ofatumumab or other targeted anti-CD20 therapies including rituximab
• Known HIV positivity
• Positive serology for Hepatitis B
• Positive serology for Hepatitis C
• Participants who are candidates for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient
• New York Heart Association Classification III of IV heart disease
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection that is not optimally treated with antibiotics, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women
• History of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancy are eligible if they have been disease-free for at least one year and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible even if diagnosed and treated within the past 1 year: localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ, breast ductal carcinoma in situ and non-melanoma skin cancers.