Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of carfilzomib, both as a single agent as well as in combination with romidepsin, in patients with cutaneous T-cell lymphoma (CTCL). SECONDARY OBJECTIVES: I. Overall response rate (ORR). II. Duration of response. III. Time to progression (TTP). TERTIARY OBJECTIVES: I. Measure proteasome activity concurrently in peripheral blood mononuclear cells (PBMCs) and tumor tissue biopsy specimens in order to gather pilot data on proteasome inhibition in CTCL patients treated with carfilzomib alone as well as carfilzomib with romidepsin. OUTLINE: This is a dose-escalation study of carfilzomib. Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16. ARM B: Patients receive carfilzomib as in Arm A and romidepsin IV over 4 hours on days 1, 8, and 15. In both arms, treatment repeats every 28 days for at least 2-4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 1 year.