6591 Background: Rituximab is a chimeric murine/human monoclonal antibody that binds to CD20 on B-lymphocytes. Interleukin-12 (IL-12) facilitates cytolytic T-cell responses and enhances the lytic activity of NK cells. This study was performed to determine the efficacy and toxicity of the combination of IL-12 and rituximab in patients with B-cell non-Hodgkin lymphoma (NHL). Methods: 52 patients with previously treated, histologically confirmed CD20+ low-grade B-cell NHL or mantle cell NHL have been enrolled in this phase 2 study. Patients were randomized to one of two arms: concurrent treatment with rituximab+IL-12 (Arm A) or rituximab with subsequent treatment with IL-12 after documented non-response, defined as less than a partial response (Arm B). Treatment consisted of rituximab 375 mg/m2 on days 1, 8, 15, and 22; and IL-12 300 ng/kg given SQ twice weekly starting on day 2 of cycle 1 for Arm A or upon progression or non-response for Arm B. We focus here on the interim analyses of the first 21 evaluable patients in each arm. Results: To date, 14 of 21 patients on Arm A and 9 of 21 patients on Arm B have discontinued treatment. 8 patients on Arm B have progressed, and have gone on to receive IL-12. On Arm A, 8 patients had grade 3 and 2 patients grade 4 toxicities vs. 2 patients on Arm B with grade 3 toxicities. Of the first 21 evaluable patients accrued to Arm A, 8 responses (38%) have been observed to date. Eight responses (38%) have also been observed on Arm B. All responses observed in Arm B were due to rituximab and none from subsequent treatment with IL-12. Based on these results, accrual to Arm B was closed. However, the subset of mantle cell NHL patients on Arm A had a higher response rate (3/5 patients). As a result, mantle cell NHL patients will continue to be accrued to Arm A. Conclusions: The combination of IL-12 and rituximab was well tolerated. The sequential administration of IL-12 at the time of disease progression after treatment with rituximab did not result in any clinical responses. The concomitant use of IL-12 and rituximab had moderate disease activity in this study; however, promising clinical activity was seen in patients with mantle cell NHL. No significant financial relationships to disclose.