This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV1CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD301 peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.81 to 66.01 months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV1CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789.