Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma
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, over...
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Published in | Experimental hematology & oncology Vol. 10; no. 1; pp. 15 - 11 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BioMed Central Ltd
18.02.2021
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 2162-3619 2162-3619 |
DOI: | 10.1186/s40164-021-00203-8 |