AUGMENT: A randomized, phase 3 trial in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) to compare efficacy and safety of lenalidomide plus rituximab (R2) versus placebo plus rituximab.

Background: The immunomodulatory drug, lenalidomide (Revlimid), has both anti-inflammatory and antiangiogenic properties. In preclinical studies, the immunological function of tumor-infiltrating lymphocytes is reduced in patients with follicular lymphoma (FL); lenalidomide can restore this response (Ramsay, Blood, 2009). In a phase 2 trial of frontline lenalidomide + rituximab (R²), the overall response rate (ORR) reached 90% (Fowler, Lancet Oncol, 2014) in iNHL patients; in a second study, patients with FL achieved 93% ORR (Martin, ICML, 2013). After treatment with R² in phase 2 investigations, patients with R/R iNHL achieved clinical responses: ORRs of 73% (36% complete response [CR]) in R/R FL (Leonard, ASCO 2012 oral presentation), and 80% (55% CR) in marginal zone lymphoma (MZL; Raderer, EHA 2014 oral presentation) patients. Based on the results of these preclinical and phase 2 studies, further investigation of R² in iNHL is warranted.Methods: This multicenter, double-blind, phase 3, randomized study (AUGMENT) is designed to evaluate the efficacy and safety of R² versus placebo + rituximab (P+R) in patients with R/R iNHL. Eligibility criteria for patients include: grade 1, 2, or 3a FL or MZL; previous treatment with systemic therapy; considered refractory to or relapsed after last treatment; rituximab-sensitivity if prior rituximab therapy was administered; presentation of ≥ 1 measurable lesion; and adequate function in bone marrow, liver, and kidneys. An estimated 350 patients will be randomized 1:1 to either experimental or control groups. Patients enrolled in the R² experimental study arm will receive lenalidomide (20 mg/day; days 1 to 21 up to 12 cycles) + rituximab (375 mg/m²; days 1, 8, 15, 22 of cycle 1 and day 1 of cycles 2 to 5) in 28-day cycles. Patients in the control study arm will receive P+R (375 mg/m²) following the same schedule. Progression-free survival is the primary endpoint, and key secondary endpoints will include rate of durable CR, overall survival, ORR, safety, and time to next anti-lymphoma treatment. Patients are currently being enrolled for this trial (NCT01938001). Clinical trial information: NCT01938001

Citation:
J Clin Oncol 33, 2015 (suppl; abstr TPS8603)

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