Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma

Patrick B. Johnston, Amanda F. Cashen, Petros G. Nikolinakos, Anne W. Beaven, Stefan Klaus Barta, Gajanan Bhat, Steven J. Hasal, Sven De Vos, Yasuhiro Oki, Changchun Deng, Francine M. Foss

Belinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK). Patients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose. Twenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1-3 schedule, resulting in escalation to Day 1-5 schedule (n = 3). No DLTs were observed and Day 1-5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent. Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing. ClinicalTrials.gov Identifier: NCT01839097.