Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

Inclusion Criteria:

Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass >= 7 cm in any uni-dimensional measurement) stage II

Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable for diagnosis
Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression
Low or intermediate risk by Follicular Lymphoma International Prognostic Index (FLIPI): 0-2 risk factors
No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy); patients may have received involved-field radiation therapy
No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease
Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable

Lesions that are considered non-measurable include the following:

Bone lesions (lesions if present should be noted)
Ascites
Pleural/pericardial effusion
Lymphangitis cutis/pulmonis
Bone marrow (involvement by NHL should be noted)
No known central nervous system (CNS) involvement by lymphoma

Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following

No evidence of coinfection with hepatitis B or C
CD4+ cell count >= 400/mm^3
No evidence of resistant strains of HIV
If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL
If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
No history of acquired immune deficiency syndrome (AIDS)-defining conditions
No evidence of active hepatitis B or C infection (i.e., no positive serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV] antibodies); hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen positive [HBsAg +]) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose
Patients with a history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome are not eligible
Patients with uncontrolled seizures are not eligible
Patients with an autoimmune disorder requires active immunosuppression are not eligible
Non-pregnant and non-nursing; females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
No known human anti-chimeric antibody (HACA) positivity
Absolute neutrophil count (ANC) >= 1,000/microliter
Platelet count >= 75,000/microliter
Creatinine clearance >= 30 mL/min unless attributable to NHL; to be calculated by method of Cockcroft-Gault, using actual weight; maximum creatinine clearance (CrCl) 125 mL/min
Total bilirubin =< 2 times upper limit of normal (ULN) unless attributable to NHL or Gilbert disease