Lenalidomide in Combination With Rituximab in Treating Participants With Stage III/IV Indolent Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To evaluate the overall response rate of lenalidomide in combination with rituximab in
previously untreated indolent non-Hodgkin's lymphoma (NHL).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of lenalidomide in combination with rituximab in previously
untreated indolent non-Hodgkin's lymphoma.

OUTLINE: Participants are assigned to 1 of 2 drug schedules.

SCHEDULE A: Participants receive lenalidomide orally (PO) on days 1-21 and rituximab
intravenously (IV) over 4-8 hours on day 1 of courses 1-12. Courses repeat every 28 days for
up to 12 courses in the absence of disease progression or unacceptable toxicity.

SCHEDULE B: Participants receive lenalidomide PO on days 2-22 and rituximab IV over 4-8 hours
on days 1, 8, 15, and 22 of course 1 and on day 1 of all subsequent courses. Courses repeat
every 28 days for up to 12 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, participants are followed up every 6 months.

Inclusion Criteria:

- Understand and voluntarily sign an informed consent form.

- Able to adhere to the study visit schedule and other protocol requirements.

- Untreated indolent non-Hodgkin's lymphoma stage III-IV including small lymphocytic
lymphoma, marginal zone lymphoma, grade 1 or 2 follicular lymphoma. (Prior radiation
for localized disease allowed).

- At least one measurable lesion according to the International workshop standardized
response criteria for non-Hodgkin's lymphomas (IWG) greater than 1.5 cm.

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry.

- Absolute neutrophil count >= 1.5 x 10^9/L.

- Platelet count >= 100 x 10^9/L.

- Serum creatinine =< 2.0 mg/dL.

- Total bilirubin =< 1.5 mg/dL.

- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and
alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2 x
upper limit of normal (ULN) or =< 5 x ULN if hepatic metastases are present.

- Disease free of prior malignancies for >= 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
or breast, or localized prostate cancer treated with curative intent.

- All study participants must be registered into the mandatory RevAssist program, and be
willing and able to comply with the requirements of RevAssist.

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10 -14 days prior to and again
within 24 hours of prescribing lenalidomide and 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 4 weeks before she starts taking lenalidomide. FCBP must also agree to
ongoing pregnancy testing.

- Men must agree to use a latex condom during sexual contact with a female of child
bearing potential even if they have had a successful vasectomy.

- For patients with bulky disease (tumors > 5 cm) must be able to take aspirin (81 mg or
325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin [ASA]
may use warfarin or low molecular weight heparin).

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

- Pregnant or breast feeding females.

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

- Use of any chemotherapy or experimental therapy within 28 days of enrollment.

- Known hypersensitivity to thalidomide.

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

- Any prior use of lenalidomide.

- Concurrent use of other anti-cancer agents or experimental treatments.

- Known positive for human immunodeficiency virus (HIV) or infectious hepatitis type B
or C. (Hepatitis B core antibody can be positive if hepatitis [Hep] B surface antigen
is negative and no hepatitis B virus [HBV] deoxyribonucleic acid [DNA] in blood,
indicating a cleared infection.)