Background: Combination of the immunomodulatory agent lenalidomide (Revlimid) with rituximab (R²) is a promising therapeutic option for patients with R/R NHL. As frontline therapy, R² provided a 90% overall response rate (ORR) in patients with follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (Fowler, Lancet Oncol, 2014) and 89% ORR in MCL patients (Ruan, ASH, 2014). In phase 2 trials of R², patients with R/R MZL, FL, and MCL achieved ORRs of 80% (55% complete response [CR]), 73% (36% CR), and 57% (36% CR), respectively (Raderer, EHA, 2014; Leonard, ASCO, 2012; Wang, Lancet Oncol, 2012). These trials support further investigation of R² therapy in R/R NHL. Methods: The efficacy and safety of 12 cycles of combination R² for induction with randomization to R² (Arm A) vs R (Arm B) maintenance will be compared in R/R FL, MCL, or MZL patients as part of the phase 3b MAGNIFY trial. Approximately 500 patients will be randomized 1:1 to 28-day (d) treatment cycles (C). Both patient groups will receive R² induction with lenalidomide (20 mg/d on d 1-21; 12 C) + R (375 mg/m² on d 1, 8, 15, 22 in C1; d1 of C 3, 5, 7, 9, 11). Patients in Arm A will receive R² maintenance with lenalidomide (10 mg/d on d 1-21; C 13-30) + R (375 mg/m² on d1 of every other C from 13 to 29), followed by lenalidomide (10 mg/d on d 1-21) until progression. Following 12 cycles of induction with R², patients in Arm B will receive maintenance R (375 mg/m² on d1 of every other C from 13 to 29). Eligibility criteria include R/R FL grades 1-3b, transformed FL, MZL, or MCL; previous systemic therapy; ≥ 1 measurable lesion; and adequate bone marrow, liver, and renal function. Progression-free survival is the primary endpoint. Secondary endpoints include rate of CR/CR unconfirmed (CRu), overall survival, ORR, duration of response, duration of CR/CRu, and safety. An exploratory endpoint, health-related quality of life will be measured using the FACT-Lym questionnaire. The MAGNIFY trial is currently enrolling; 38 patients have been enrolled as of January 30, 2015 (NCT01996865). Clinical trial information: NCT01996865