Inclusion Criteria:

Registration: Patients having both diffuse and follicular architectural elements will be
considered eligible if the histology is predominantly follicular (≥ 50% of the
cross-sectional area), and there is no evidence of transformation to a large cell
histology.

- Biopsy-proven diagnosis of Grade 1 or 2 follicular non-Hodgkin's lymphoma with no
evidence of transformation to large cell histology.

- Meet criteria for Low Tumor Burden:

- No nodal or extra nodal mass ≥ 7 centimeter (cm)

- <3 nodal masses >3 cm in diameter

- No systemic symptoms or B symptoms

- No splenomegaly >16 cm by CT scan

- No risk of compression of a vital organ.

- No leukemic phase with >5000/mm³ circulating lymphocytes.

- No cytopenias defined as:

- Platelets <100,000/mm³

- Hemoglobin (Hgb) <10 g/dL

- Absolute Neutrophil Count (ANC) <1500/mm³

- Must have Stage III or Stage IV disease.

- Baseline measurements/evaluations obtained within 6 weeks of registration. Patient
must have at least one objective measurable disease parameter.

- Age ≥ 18 years.

- Eastern Oncology Cooperative Group Performance Status 0-1.

- Must not have received investigational agents within 30 days of registration.

- Signed Institutional Review Board (IRB)-approved informed consent.

- Willing to provide blood samples for research purposes.

- Women must not be pregnant or breastfeeding.

- Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception.

- No prior chemotherapy, radiotherapy or immunotherapy for lymphoma.

- No prior treatment with cytotoxic drugs or rituximab for another condition (e.g.
rheumatoid arthritis) or prior use of an anti-CD20 antibody.

- No prior use of any monoclonal antibody within 3 months of randomization.

- No history of severe allergic/anaphylactic reactions to humanized/murine monoclonal
antibodies or known sensitivity/allergy to murine products.

- No history of prior malignancy except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
been disease-free for at least 2 years.

- No major surgery within 4 weeks prior to randomization, other than for diagnosis.

- Must be Human Immunodeficiency Virus (HIV) negative.

- Have adequate organ function without growth factor and/or transfusion support within
≤ 2 weeks prior to registration:

- ANC ≥ 1500/mm³

- Hgb ≥ 10 g/dL

- Platelets ≥ 100,000/mm³

- Serum Creatinine ≤ 2x Upper Limit Normal (ULN)

- Total Bilirubin ≤ 2x ULN

- AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ≤ 5x ULN

- PTT (Partial Thromboplastin Time) or aPTT (activated Partial Thromboplastin
Time) >1.5x the ULN in the absence of a lupus anticoagulant

- INR (International Normalized Ratio) >1.5x the ULN in the absence of therapeutic
anticoagulation

- No active, uncontrolled infections (afebrile for ≥ 48 hours off antibiotics).

- Must not receive immunization with attenuated live vaccines within 28 days prior to
registration or during the study period.

- Must be tested for hepatitis B surface antigen (HBsAg) and total hepatitis B core
antibody (anti-HBc) within 2 weeks of registration. Patients who are chronic carriers
of HBsAg and anti-HBc are excluded.

- Must be tested for hepatitis C antibody within 2 week of registration. If this test
is positive, patients are excluded unless a hepatitis C virus ribonucleic acid (HCV
RNA) is negative.

- No evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (i.e., severe arrhythmia, myocardial infarction within the
previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease.