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

ABSTRACT:

Background

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).

Methods

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.

Results

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.

Conclusions

Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing.

Trial registration

ClinicalTrials.gov Identifier: NCT01839097.

SUBMITTER: Johnston PB 

PROVIDER: S-EPMC7893947 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature