A Phase II Trial of Lenalidomide (Revlimid (TM), CC-5013) (NSC #703813, IND#70116) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

Inclusion Criteria:

- Histologically* confirmed follicular non-Hodgkin lymphoma (NHL)

- WHO grade 1, 2, or 3a (> 15 centroblasts per high-power field with centrocytes
present) disease

- Stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional
measurement) stage II disease

- Previously untreated disease

- CD20-antigen expression as confirmed by institutional flow cytometry or IHC

- Low- or intermediate-risk disease by Follicular Lymphoma International Prognostic
Index (FLIPI) (i.e., 0-2 risk factors)

- Measurable disease on either physical examination or imaging studies

- Any tumor mass > 1 cm is allowed

- Non-measurable disease alone is not allowed

- Lesions that are considered non-measurable include, but are not limited to, 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 CNS involvement by lymphoma

- ECOG performance status 0-2

- ANC ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

- Creatinine clearance ≥ 30 mL/min (unless attributable to NHL)

- Total bilirubin ≤ 2 times upper limit of normal (unless attributable to NHL or
Gilbert disease)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use two effective methods of contraception for ≥ 28 days
before, during, and for ≥ 3 months after completion of study treatment

- No history of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson
syndrome

- No uncontrolled seizures

- No autoimmune disorder requiring active immunosuppression

- Patients with HIV infection are eligible, provided they meet the following criteria:

- 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 AIDS-defining conditions

- No evidence of active hepatitis B or C infection (i.e., no positive serology for
anti-HBc or anti-HCV antibodies)

- HBV-seropositive patients (HBsAg +) are eligible provided they are closely
monitored for evidence of active HBV infection by HBV DNA testing and receive
suppressive therapy with lamivudine or other HBV suppressive therapy until 6
months after the last dose of rituximab

- No known human anti-chimeric antibody (HACA) positivity

- Not on dialysis

- No other concurrent investigational or non-protocol therapy for lymphoma

- No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g.,
monoclonal antibody-based therapy)

- Prior involved-field radiotherapy allowed

- More than 2 weeks since prior corticosteroids, except for maintenance therapy for a
nonmalignant disease

- No concurrent dexamethasone and other steroids as antiemetics