Background: Salvage regimens for Hodgkin lymphoma (HL) can be challenging due to either need for inpatient admission or frequent dosing. Based on previously reported single agent activity of bendamustine (benda) and gemcitabine (gem), we conducted a phase I study of benda and gem in patients (pts) with relapsed/refractory classical HL who failed at least 1 prior therapy to determine the maximum tolerated dose. Methods: Utilizing a cohorts of 3 design, pts received gem dosed at 1000mg/m² on day 1 and benda doses of 60mg/m² to 120mg/m²on days 1 and 2 of each cycle for up to 6 cycles, with cycle lengths of 28 (dose levels [DL] 1-3) and 21 (DL 4-5) days. Dose limiting toxicity (DLT) was determined during cycle 1. Results: Fourteen pts (8 males) with a median age of 38.5 years (range: 23-60) and a median of 4 (range: 1-7) prior lines of therapy have completed a median of 4 cycles at DL 1 (n = 3), 2 (n = 3), 3 (n = 3), 4 (n = 4), and 5 (n = 1). Seven pts had a prior autologous transplant (ASCT), and 1 pt had a prior ASCT and allogeneic transplant. One pt only received day 1 of therapy in cycle 1 at DL 4 and was thus not considered in dose escalation determination. The benda dose was 60mg/m² for 3 pts, 90mg/m² for 6 pts, and 120mg/m² for 4 pts. No DLTs have been observed. Four pts have required hospitalization, including 2 heavily pretreated pts with pulmonary symptoms after cycle 2. One underwent a biopsy that was consistent with a drug-induced pneumonitis likely gem-related, while the other had grade 5 respiratory failure that was deemed secondary to infection although a relationship with gem could not be ruled out. Additional grade 3-4 toxicities include: lymphopenia (n = 10) thrombocytopenia (n = 2), atrial fibrillation (n = 1), fever (n = 1), renal failure (n = 1), hypotension (n = 1), pneumonia (n = 1), hypoalbuminemia (n = 1), hypokalemia (n = 1), and rash (n = 1). In 13 evaluable pts, the response rate was 77% (CR, n = 3; PR, n = 7; SD, n = 2; PD, n = 1). Two pts have had an ASCT with collection of 5.1 x 10⁶ CD34+ cells over 2 days and 4.94 x 10⁶CD34+ cells over 3 days. Conclusions: The combination of benda 120mg/m² with gem 1000mg/m² is tolerable and appears efficacious. We continue to monitor closely for additional pulmonary toxicity as we complete accrual to our final dose level using a 21-day cycle. Clinical trial information: NCT01535924