This Phase 3B multicenter, randomized (stratified by histology, lines of anti-lymphoma therapy and age), open label study will enroll subjects with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL) or mantle cell lymphoma (MZL). All subjects will receive 12 Cycles of lenalidomide plus rituximab induction therapy. The study is designed to compare the efficacy and safety of two maintenance regimens following induction therapy. Subjects will be randomized at study start to lenalidomide plus rituximab combination therapy (for 18 Cycles) followed by lenalidomide single-agent maintenance (to progression; Arm A, experimental) versus rituximab single-agent maintenance (for 18 Cycles; Arm B, control). The study is divided into a Screening Period, a Treatment Period (induction and maintenance), and a Follow up Period. Approximately 500 subjects are planned to be randomized.
Follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) are cancers of the B lymphocyte, a type of white blood cell. Lenalidomide is an immunomodulatory drug (a drug that affects the immune system) which alters the body's immune system and it may also interfere with the development of tiny blood vessels involved in tumor growth. Therefore, lenalidomide may reduce or prevent the growth of cancer cells. Lenalidomide has also been shown to restore the immune cells' ability to attack and kill tumor cells, an ability that may be inhibited by FL and other lymphomas. The combination of rituximab and lenalidomide may eliminate the cancer while restoring the immune system's ability to attack tumor cells.
Subjects must have an investigator assessed diagnosis of relapsed/refractory Grade 1, 2, or 3a follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), Stage I to IV, have been previously treated for their lymphoma with at least one prior line of systemic chemotherapy, immunotherapy, or chemoimmunotherapy; have at least one measurable nodal or extranodal lesion by computed axial tomography (CT) or magnetic resonance imaging (MRI) scan, and have adequate bone marrow function, liver function, and renal function.
Subjects with either follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) will be randomized to Arm A will receive lenalidomide plus rituximab for up to 30 Cycles (12 induction Cycles then 18 maintenance Cycles) followed by lenalidomide single-agent maintenance (to disease progression [PD]).
Subjects with either follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) will be randomized to Arm B will receive lenalidomide plus rituximab for 12 Cycles (induction) followed by rituximab single-agent for 18 Cycles (maintenance). Cycle length in both arms is 28-days.
Efficacy determination for the primary endpoint will be based upon progression free survival (PFS).