Background: Front-line therapy for B-cell NHL incorporates chemotherapy and Rituximab (R). Unfortunately, pts often relapse. Bendamustine (B) and Lenalidomide (L) each have efficacy in lymphoma, but their combination has yet to be studied. In this 2-stage phase I study, we proposed combining BL in relapsed/refractory lymphoid malignancies (Stage I) in order to determine the MTD of L for future combination of BLR in B-cell NHL (Stage II). Methods: Pts with relapsed/refractory NHL or Hodgkin lymphoma (HL) with adequate performance status and organ function were eligible. This phase I study utilized a 3 + 3 dose-escalation design. In Stage I pts received B 90 mg/m² IV on D1, 2 with escalating doses of L (5, 10, 15, 20 mg) po daily of each 28-day cycle. Pts received 6 cycles of BL followed by 6 cycles of L as long as tolerated or until progressive disease (PD). As many pts were noted to have PD, an unplanned interim analysis of Stage I was done. Safety is under evaluation by the DSMB. Results: Of the 7 pts on study, the median age was 52 years, 43% were male, and all were Ann Arbor Stage III/IV. Histologies included DLBCL (3), HL (2), follicular with transformation (1), and cutaneous T-cell (1). An MTD has not yet been reached for L. The second pt enrolled had a DLT of grade 3 rash. Thus, the third pt started at a lower dose of 5 mg every other day. As rash is common with L, the protocol was subsequently amended so that L was given only 21 days of each cycle. In addition, only grade 4 rash or grade 3 rash that did not resolve to < grade 2 within 10 days despite steroids were to be considered DLTs. After these amendments, the trial was reset and 3 new pts were enrolled into Cohort 1 at L 5 mg daily. The first pt in this cohort died during cycle 1 due to PD and was replaced by a fourth. No further DLTs or grade 3/4 rash were noted. Common grade 3/4 toxicities were anemia (57%), leucopenia (57%), and neutropenia (43%). Six of the 7 pts had PD on BL. One pt (DLBCL) had a CR by 2 months and went to transplant. Pts completed a median of 2 cycles of therapy. Most pts withdrew for PD. Conclusions: BL appears to be tolerable in relapsed/refractory lymphoma. Preliminary data suggests limited efficacy but further evaluation is necessary. Additional pts are being accrued to determine the MTD of L prior to adding R in B-cell NHL.