Background: Salvage therapy followed by autologous stem cell transplantation improves outcomes for patients with primary refractory Hodgkin lymphoma (HL) or early relapse. Brentuximab vedotin (Bv) and gemcitabine each produce high overall response rates in this context. Compared to alternate retrieval regimens, this combination offers the advantage of avoiding agents that are associated with late treatment sequelae, such as anthracyclines, alkylators, or epipodophyllotoxins. This phase 1 trial was conducted to describe the toxicity of the combination and to define a recommended phase 2 dose (RP2D) for Bv when given with gemcitabine. Methods: Patients ≤ 30 years old with primary refractory HL or early relapse were eligible. Bv was given on day 1 of each 21-day cycle, at two dose levels (DL): DL1, 1.4 mg/kg and DL2, 1.8 mg/kg. Gemcitabine 1000mg/m² was given on day 1 and 8. Dose limiting toxicity (DLT) was assessed during cycle 1 to define the RP2D, and response after every 2 cycles. Results: Fifteen patients have enrolled (14 evaluable for hematologic toxicity), with median age of 17 years (range 5-28). No DLTs were seen among 3 patients treated at DL1. Two of six patients experienced non-hematologic DLT at DL2: one with grade 3 hypotension and one with asymptomatic Grade 3 elevation of liver enzymes. Both had resolution of all toxicity and continued on study treatment with dose reduction of Bv to 1.2 mg/kg. An expansion cohort of six patients was enrolled at DL2; none experienced DLT. Grade 3-4 neutropenia was common (13 of 14 patients during cycle 1) but self-limited. No grade 4 non-hematologic toxicity occurred. No cases of interstitial pneumonitis or pulmonary toxicity attributable to study therapy were observed. Conclusions: Bv can be safely given in combination with gemcitabine. The RP2D of Bv is 1.8 mg/kg. The ongoing Phase 2 trial will describe the complete response rate observed within four cycles of Bv with gemcitabine. Clinical trial information: NCT01780662. Clinical trial information: NCT01780662