Rituximab and/or Lenalidomide in Treating Patients With Follicular Non-Hodgkin's Lymphoma That is Not Refractory to Rituximab

Outline:

This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.
Please see the "Arms" section for a description of each treatment arm. The primary and
secondary objectives of the study are provided below.

Primary Objectives:

- To determine the response rate (overall and complete) after lenalidomide therapy and
rituximab + lenalidomide in follicular NHL patients who have relapsed.

- To determine time to progression after lenalidomide therapy and rituximab and
lenalidomide in follicular NHL patients who have relapsed.

Secondary Objectives:

- To compare the time to progression of the previous rituximab regimen to that obtained
subsequently to lenalidomide therapy and rituximab + lenalidomide.

- To determine the toxicity profile of lenalidomide therapy and of rituximab and
lenalidomide in follicular NHL patients who have received a previous rituximab regimen.

- To correlate Fc receptor polymorphism profiling with response to lenalidomide or
rituximab + lenalidomide in previously treated patients with follicular NHL who have
relapsed.

- To evaluate changes in Natural Killer (NK) cells, activated NK cells, activated T-cells
and several plasma cytokines followed by rituximab therapy and correlation of observed
changes to objective response rates.

After completion of study treatment, patients are followed for up to 10 years from study
entry.

- Documentation of Disease

- Previously treated, histologically confirmed follicle center cell lymphoma,
World Health Organization (WHO) classification, grade 1, 2, or 3a

- Institutional flow cytometry or immunohistochemistry must confirm Cluster of
Differentiation 20 (CD20) antigen expression.

- Prior Treatment

- Patient must have been treated with rituximab either alone or in combination
with chemotherapy.

- Patient must have a time to progression of ≥ 6 months from last rituximab dose.

- No corticosteroids within two weeks prior to study, except for maintenance
therapy for a non-malignant disease. Maintenance therapy dose may not exceed 20
mg/day prednisone or equivalent.

- No prior radioimmunotherapy within 12 months of study entry.

- Age ≥ 18 years.

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

- 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

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Bone marrow

- No known Central Nervous System (CNS) involvement by lymphoma.

- No known Human Immunodeficiency Virus (HIV) infection.

- Non-pregnant and non-nursing.

- Patients with a "currently active" second malignancy, other than non-melanoma skin
cancers, are not eligible.

- Patients with a recent history (within 3 months of study entry) of Deep Vein
Thrombosis/Pulmonary Embolism (DVT/PE) are not eligible.

- Required Initial Laboratory Values:

- Absolute Neutrophil Count (ANC) ≥ 1000/µL

- Platelet count ≥ 75,000/µL

- Creatinine < 1.5 x Upper Limit of Normal (ULN) unless attributed to lymphoma or
calculated clearance > 50 mL/min (patients on dialysis are not eligible)

- Total Bilirubin ≤ 2 x ULN unless attributed to lymphoma or Gilbert's disease