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Johnston PB , Cashen AF , Nikolinakos PG , Beaven AW , Barta SK , Bhat G , Hasal SJ , De Vos S , Oki Y , Deng C , Foss FM
Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma
Exp Hematol Oncol. 2021 Feb 18;10(1) :15
PMID: 33602316    PMCID: PMC7893947   
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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/m(2) 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/m(2) 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.
Notes
2162-3619 Johnston, Patrick B Cashen, Amanda F Nikolinakos, Petros G Beaven, Anne W Barta, Stefan Klaus Bhat, Gajanan Hasal, Steven J De Vos, Sven Oki, Yasuhiro Deng, Changchun Foss, Francine M Journal Article Exp Hematol Oncol. 2021 Feb 18;10(1):15. doi: 10.1186/s40164-021-00203-8.