This phase II trial studies the side effects and how well giving pegfilgrastim together with rituximab works in treating patients with untreated, relapsed, or refractory follicular lymphoma, small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL). Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of therapy. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or tumor cancer-killing substances to them. Giving pegfilgrastim together with rituximab may kill more cancer cells

PRIMARY OBJECTIVES:

I. To evaluate the safety of Pegfilgrastim in combination with rituximab in patients with untreated or relapsed/refractory follicular, SLL or MZL.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy (including overall response rate and durability of objective responses) of Pegfilgrastim in combination with rituximab in patients with untreated or relapsed/refractory follicular, SLL or MZL.

II. To evaluate functional and phenotypic characteristics of host neutrophils undergoing treatment with Pegfilgrastim and rituximab.

III. To evaluate changes in cluster of differentiation (CD)20 antigen expression and density of expression in patients receiving Pegfilgrastim and rituximab.

IV. To evaluate changes in serum levels of tumor necrosis factor (TNF), interferon alpha (INFalpha) and free radical levels in patients undergoing treatment with Pegfilgrastim and rituximab.

OUTLINE:

Patients receive pegfilgrastim subcutaneously (SC) followed by rituximab intravenously (IV) 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and then yearly for 1 year.

Inclusion Criteria:

• Untreated or relapsed/refractory follicular, SLL or MZL (i.e. no limit to number of prior treatments as long as patients meet other study criteria)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Measurable tumor size (at least one node measuring 4 cm^2 in bidimensional measurement)
• Expected survival of > 6 months
• Prior rituximab or other monoclonal immunotherapy permitted and eligible for rituximab monotherapy
• Full recovery from any significant toxicity associated with prior surgery, radiation therapy, chemotherapy, or immunotherapy
• Absolute neutrophil count > 1.0 x 10^9/L
• Platelets > 50 x 10^9/L
• Patients may receive erythropoietin growth factors to maintain adequate hemoglobin levels (>= 8.0 mg/dl)
• Creatinine < 1.5 x upper normal levels (UNL)
• Total bilirubin < 1.5 mg/dL (> 25.65 umol/L)
• Aspartate aminotransferase < 5 x UNL
• Alkaline phosphatase < 5 x UNL
• Informed consent approved in institutional review board (lRB)
• CD20+ B-cell lymphoma

Exclusion Criteria:

• Prior history of human immunodeficiency virus (HIV)-positivity (routine HIV testing is required pretreatment)
• Serious non-malignant disease (e.g. active uncontrolled bacterial, viral, or fungal infections) or other conditions which, in the opinion of the principal investigator would compromise other protocol objectives
• Presence of central nervous system (CNS) lymphoma
• Chemotherapy within 4 weeks of the first scheduled study treatment
• Another primary malignancy (other than squamous or basal cell carcinoma of the skin or in-situ carcinoma of the cervix) for which the patient has not been disease-free for at least five years
• Major surgery, other than diagnostic surgery, within four weeks
• Patients with non-Hodgkin lymphoma (NHL) other than relapsed/refractory follicular, MZL or SLL
• Patients must not have a history of cardiac disease, defined as New York Heart Association Class II or greater or clinical evidence of congestive heart failure
• Concurrent use of other investigational agents
• Pregnant or breast feeding
• Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator
• Known hypersensitivity to any recombinant E coli-derived product, murine proteins, or any components of the study medications
• Concerns for the subject's compliance with the protocol
• Any premalignant myeloid condition or any malignancy with myeloid characteristics (e.g. myelodysplastic syndromes, acute or chronic myelogenous leukemia)
• Patient is currently enrolled in, or has not yet completed at least 30 days since ending another investigational device or drug trial