Patrick B Johnston1, Amanda F Cashen2, Petros G Nikolinakos3, Anne W Beaven4, Stefan Klaus Barta5, Gajanan Bhat6, Steven J Hasal6, Sven De Vos7, Yasuhiro Oki8, Changchun Deng9, Francine M Foss10. 1. Mayo Clinic, 200 first St SW, Rochester, MN, 55905, USA. johnston.patrick@mayo.edu. 2. Division of Oncology, Washington University Medical School, 660 S. Euclid Ave, Campus, Box 8007, St Louis, MO, 63110, USA. 3. University Cancer and Blood Center, 3320 Old Jefferson Rd #700, Athens, GA, 30607, USA. 4. Duke University School of Medicine, 2592 Morris Bldg, Box 3406, Durham, NC, 27710, USA. 5. Dept of Hematology/Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. 6. Spectrum Pharmaceuticals, 157 Technology Dr, Irvine, CA, 92618, USA. 7. Cancer Care, Ronald Reagan University of California At Los Angeles Medical Center, 2020 Santa Monica Blvd, Santa Monica, CA, 90404, USA. 8. Dept of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0429, Houston, TX, 77030, USA. 9. Center for Lymphoid Malignancies, Columbia University Medical Center, 51 West 51st St, New York, NY, 10019, USA. 10. Medical Oncology, Yale Cancer Center, 333 Cedar St, TMP 3, PO Box 208028, New Haven, CT, 06510, USA.
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.
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.
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