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

• Published in: Experimental hematology & oncology Vol. 10; no. 1; pp. 15 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.02.2021; BioMed Central; BMC
• Subjects: Anthracyclines; Antimitotic agents; Antineoplastic agents; Belinostat; Bone marrow; Care and treatment; Cell cycle; Chemotherapy; CHOP; Corticosteroids; Cyclophosphamide; Histone deacetylase inhibitor (HDACi); Laboratories; Lymphoma; Nausea; Non-Hodgkin's lymphomas; Patients; Peripheral T-cell lymphoma (PTCL); Prednisone; Response rates; Stem cells; T cells; United States > US; CHOP; Peripheral T-cell lymphoma (PTCL); Histone deacetylase inhibitor (HDACi); Belinostat
• ISSN: 2162-3619; 2162-3619
• DOI: 10.1186/s40164-021-00203-8

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/m 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/m 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.