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.