The purpose of this clinical trial is to see if increased doses of rituximab are safe and effective for the initial treatment of indolent B-cell lymphomas. Rituximab (Rituxan) is a type of drug called an "antibody" that specifically targets B-cell lymphoma cells, and is approved by the FDA for the treatment of indolent B-cell non-hodgkin lymphomas and certain other types of non-hodgkin lymphomas. Standard doses currently used may not be achieving maximal efficacy. Higher doses have been shown to be safe in other clinical trials, and may offer superior efficacy to the current standard dose. This trial also employs intermittent maintenance doses of rituximab at the standard dose, which has been shown to prolong remissions and survival in patients with relapsed indolent B-cell lymphomas. This trial is designed to show that higher dose rituximab plus maintenance rituximab can achieve similarly good results to chemotherapy approaches, but without chemotherapy-related toxicity.

• All participants will receive increased-dose rituximab through a vein in the arm once a week for 4 weeks (on Days 1, 8, 15, and 22 of the initial 28-day study cycle). This first cycle of study treatment is called the Induction Phase. If the participant responds well to the Induction Phase, they then may continue to the Maintenance Therapy Phase, where they will receive a lower dose of rituximab once every three months for up to 2 years.
• During the Induction Phase, the following procedures will take place before the participant receives each dose of rituximab: medical review, physical exam, performance status, and ECG. Blood tests will be drawn about 30-60 minutes after the first dose of rituximab on Day 1. Samples will be drawn immediately before each dose and again 30-60 minutes after each dose on Days 1, 8, 15 and 22.
• During the Maintenance Therapy Phase, the following procedures will take place before the participant receives each dose of rituximab: medical review, physical exam, performance status, ECG, blood tests and response assessments by CT scan.

Inclusion Criteria:

• Indolent B-Cell NHL of the following histologies:

  1. Follicular lymphoma (grades 1-3A);

  2. marginal zone lymphoma (extranodal, nodal or splenic):

     • Extranodal marginal zone lymphomas (MALT lymphomas) may not be candidates for cure with antibiotics or local radiotherapy. Patients who have failed antibiotics or local therapy are eligible for the protocol as long as they have measurable disease and are naive to chemotherapy and monoclonal antibody;
     • splenic marginal zone lymphoma patients may have received prior splenectomy as long as they have measureable disease and are naive to chemotherapy and monoclonal antibody therapy;

  3. Small lymphocytic lymphoma (must have less than 5000 circulating clonal B-lymphocytes);

  4. Indolent CD20+ 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 (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan

• No previous chemotherapy, antibody therapy or radioimmunotherapy for NHL. Patients previously treated with external bean radiation alone, surgery, or with antibiotics are eligible

• 18 years of age or older

• Life expectancy of greater than 3 months

• ECOG performance status of 2 or less

• Adequate bone marrow function

• Use of adequate contraception

Exclusion Criteria:

• Prior chemotherapy, monoclonal antibody therapy or radioimmunotherapy for lymphoma

• Receiving any other investigational agent

• Known brain metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab

• HIV positivity

• Active hepatitis B infection

• Candidate for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient

• NYHA Classification III or IV 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 women

• Individuals with a history of a different malignancy except for the following circumstances:

  1. disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy;
  2. localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ; and
  3. non-melanoma skin cancers