Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study Journal Article


Authors: O'Connor, O. A.; Horwitz, S.; Masszi, T.; Van Hoof, A.; Brown, P.; Doorduijn, J.; Hess, G.; Jurczak, W.; Knoblauch, P.; Chawla, S.; Bhat, G.; Choi, M. R.; Walewski, J.; Savage, K.; Foss, F.; Allen, L. F.; Shustov, A.
Article Title: Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study
Abstract: Purpose: Peripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL. Patients and Methods: Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m2 as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included duration of response (DoR) and progression-free and overall survival. Results: A total of 129 patients were enrolled, with a median of two prior systemic therapies. Overall response rate in the 120 evaluable patients was 25.8% (31 of 120), including 13 complete (10.8%) and 18 partial responses (15%). Median DoR by International Working Group criteria was 13.6 months, with the longest ongoing patient at ≥ 36 months. Median progression-free and overall survival were 1.6 and 7.9 months, respectively. Twelve of the enrolled patients underwent stem-cell transplantation after belinostat monotherapy. The most common grade 3 to 4 adverse events were anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), and neutropenia (6.2%). Conclusion: Monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication. © 2015 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; treatment response; aged; major clinical study; overall survival; prednisone; drug tolerability; neutropenia; cancer recurrence; doxorubicin; cancer combination chemotherapy; drug dose reduction; drug efficacy; drug withdrawal; gastrointestinal hemorrhage; monotherapy; side effect; systemic therapy; cancer patient; progression free survival; multiple cycle treatment; phase 2 clinical trial; thrombocytopenia; qt prolongation; creatinine; cyclophosphamide; vincristine; creatinine blood level; hematopoietic stem cell transplantation; dyspnea; febrile neutropenia; fever; pneumonia; liver failure; peripheral t cell lymphoma; heart failure; multicenter study; shock; cancer fatigue; open study; corticosteroid; lung infection; drug treatment failure; pralatrexate; belinostat; corticosteroid therapy; toxic hepatitis; chemotherapy induced anemia; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 33
Issue: 23
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2015-08-10
Start Page: 2492
End Page: 2499
Language: English
DOI: 10.1200/jco.2014.59.2782
PROVIDER: scopus
PUBMED: 26101246
PMCID: PMC5087312
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Steven M Horwitz
    344 Horwitz