This is single-center, open-label, prospective phase I/II clinical trial evaluating the safety, efficacy, and pharmacokinetics of Carfilzomib + standard R-ICE combination therapy in adult patients with relapsed/refractory diffuse large B-cell lymphoma. The statistical design is based on a dose-finding algorithm to determine the maximal tolerated dose (MTD) of the study regimen and an assessment of the efficacy of the treatment for patients as compared to an external standard, i.e. R-ICE historical control. All enrolled patients will receive the study drug and initiation of the treatment should take place as soon as possible following study enrollment. A total of up to 36 evaluable patients will be enrolled in the Phase I component, and a total of up to 37 evaluable patients will be enrolled in the Phase II portion of the study.