title: Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m(2) 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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA. oo2130@columbia.edu.
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Steven
authors.initials: S
authors.lastname: Horwitz
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Tamás
authors.initials: T
authors.lastname: Masszi
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Achiel
authors.initials: A
authors.lastname: Van Hoof
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Doorduijn
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jurczak
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Poul
authors.initials: P
authors.lastname: Knoblauch
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Shanta
authors.initials: S
authors.lastname: Chawla
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Gajanan
authors.initials: G
authors.lastname: Bhat
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Mi Rim
authors.initials: MR
authors.lastname: Choi
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Jan
authors.initials: J
authors.lastname: Walewski
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Savage
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Francine
authors.initials: F
authors.lastname: Foss
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Lee F
authors.initials: LF
authors.lastname: Allen
authors.affiliation: Owen A. O'Connor, Columbia University Medical Center; Steven Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Tamás Masszi, St Istvan and St Laszlo Hospital, Budapest, Hungary; Achiel Van Hoof, General Hospital St-Jan, Brugge, Belgium; Peter Brown, Rigshospitalet; Poul Knoblauch, Topotarget, Copenhagen, Denmark; Jeannette Doorduijn, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Georg Hess, Johannes Gutenberg-University, Mainz, Germany; Wojciech Jurczak, Jagiellonian University, Krakow; Jan Walewski, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland; Shanta Chawla, Gajanan Bhat, Mi Rim Choi, and Lee F. Allen, Spectrum Pharmaceuticals, Irvine, CA; Kerry Savage, British Columbia Cancer Agency Centre, Vancouver, British Columbia, Canada; Francine Foss, Yale Cancer Center, New Haven, CT; and Andrei Shustov, University of Washington Medical Center, Seattle, WA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Shustov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013449:Sulfonamides; C487081:belinostat