Belinostat in Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)

A Multicenter, Open-Label Trial of Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma

The purpose of this study is to assess efficacy and safety of belinostat in participants with relapsed or refractory peripheral T-cell lymphoma (PTCL), who failed at least one prior systemic therapy.

Study Overview

• Status: Completed
• Conditions: Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: Belinostat

Detailed Description

This is an open-label, multicenter, single arm efficacy and safety study in participants with relapsed or refractory peripheral T-cell lymphoma, who have failed at least one prior systemic therapy.

Approximately 120 participants will be enrolled. Participants will be treated with 1000 mg/m^2 belinostat administered as a 30-minute IV infusion on Days 1-5 of every 3-week cycle until there is disease progression or unmanageable treatment-related toxicities.

The primary study endpoint is objective response rate (ORR) based on the International Harmonization Project (IHP) revision International Working Group (IWG) criteria. Safety will be evaluated during the study and for 30 days after the last administration of study drug. Adverse events and laboratory studies will be graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 3.0.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2020
    • ZNA Middelheim
  • Antwerpen, Belgium, 2060
    • ZNA Stuivenberg
  • Bruxelles, Belgium, 1200
    • Clinique Universitaire Saint Luc, Service Hématologie
  • Brügge, Belgium, 8000
    • AZ St. Jan
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Liege, Belgium, 4000
    • University of Liege, Divisions of Hematology and Medical Oncology
  • Yvoir, Belgium, 5530
    • Cliniques Universitaires UCL Mont Godinne, Service Hématologie
• Canada
  • Montreal, Canada, H2W1S6
    • McGill University
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • University of British Columbia
  • Quebec
    • Quebec City, Quebec, Canada, G1J1Z4
      • CHA Hôpital de l'Enfant-Jésus
• Croatia
  • Split, Croatia, 21000
    • CHC Split Clinic of Internal Diseases
  • Zagreb, Croatia, 10000
    • CHC Zagreb Clinic of Internal Diseases
  • Zagreb, Croatia, 10000
    • UH Dubrava Clinic of Internal Diseases
  • Zagreb, Croatia, 1000
    • CHC Rijeka, Clinic of Internal Diseases
• Denmark
  • Copenhagen, Denmark, 2100
    • H:S Rigshospitalet, The Finsen Centre, KAT, Haematology Department 4241
• France
  • Nice, France, 6202
    • Hôpital de l'Archet, Centre Hospitalier Universitaire (CHU) de Nice, Hématologie Clinique
  • Saint-Pierre Cedex, France, 97448
    • Groupe Hospitalier Sud Réunion, Site Saint-Pierre
• Germany
  • Essen, Germany, 45239
    • Klinik Essen Süd, Evangelisches Krankenhaus
  • Frankfurt, Germany, 60488
    • Leitender Oberarzt/Klinik für Onkologie und Hämatologie
  • Göttingen, Germany, 37075
    • Universität Göttingen, Abteilung Hämatologie und Onkologie
  • Halle, Germany, 06120
    • Universitätsklinikum (AöR) der Martin-Luther-Universität Halle-Wittenberg
  • Hamburg, Germany, 20099
    • Asklepios Klinik St. Georg
  • Homburg/Saar, Germany, 66424
    • Universitatsklinikum des Saarlandes
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig AöR
  • Mainz, Germany, 55131
    • Universitätsmedizin der johannes Gutenberg -Universität Mainz
  • Marburg, Germany, 35043
    • University Hospital Marburg
  • München, Germany, 81675
    • Münchner Studienzentrum Klinikum Rechts der Isar
  • Nuernberg, Germany, 90419
    • Klinikum Nuernberg Nord
  • Rostock, Germany, 18057
    • Universitätsklinikum Rostock
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Hungary
  • Budapest, Hungary, 1097
    • Szt István és Szt. Laszlo
  • Debrecen, Hungary, 4032
    • Belgyógyászati Klinika
  • Györ, Hungary, 9042
    • Belgyógyászati Klinika Györ
  • Szeged, Hungary, 6720
    • Belgyógyászati Klinika es Kardiologial Központ
• Israel
  • Beer Sheva, Israel, 84101
    • The Soroka University Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center Department of Hematology
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital Sharet Building Department of Hematology
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center Belinson Campus
• Italy
  • Bologna, Italy, 40138
    • Ospedale Sant'Orsola, Instituto di Ematologia e Oncologia Medica
  • Firenze, Italy, 50134
    • Ospedale Policlinico Careggi
• Netherlands
  • Amsterdam, Netherlands, 7081 HV
    • VU Medical Center, Department of Haematology
  • Groningen, Netherlands, 9700
    • University Medical Center Groningen UMCG, Department of Haematologie
  • Rotterdam, Netherlands, 3015
    • Erasmus University Medical Center
  • Zwolle, Netherlands, 8025 AB
    • Isala Clinics, Department of Haematololgy
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne Klinika Hematologii I Transplantologii
  • Kraków, Poland, 30-510
    • Małopolskie Centrum Medyczne
  • Opole, Poland, 45-051
    • Szpital Wojewódzki w Opolu/Oddział Hematologii
  • Warszawa, Poland, 02-106
    • MTZ Clinical Research Sp z o.o.
  • Warszawa, Poland, 02-776
    • Instytut Hematologii I Transfuzjologii Klinika Hematologii
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny Klinika Chorób/Wewnętrznych i Hematologii Centralnego Szpitala
  • Łódź, Poland, 93-510
    • Wojewódzki Szpital Specjalistyczny im M. Kopernika w Łodzi Oddział Hematologii - Klinika Hematologii
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Klinika Nowotworów Ukladu Chlonnego Centrum Onkologii Instytut Marii Sklodowskiej-Curie
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • State Therapeutical and Prophylactic Institution Chelyabinsk Regional Clinical Oncology Dispensary
  • Moscow, Russian Federation, 115478
    • Russian Cancer Research Centre named after N.N. Blokhin of Russian Academy of Medical Sciences
  • Moscow, Russian Federation, 125167
    • Research Center of Haematology
• Slovakia
  • Bratislava, Slovakia, 83310
    • Narodny Onkologicky Ustav (NOU)
  • Kosice, Slovakia, 04066
    • Klinika Hematologie a Onkohematologie FNLP a LF UPJS
• South Africa
  • Bellville, South Africa, 7505
    • Tygerberg Hospital, Department of Radiation Oncology
  • Durban, South Africa, 4126
    • Drs pirjol, Szpak and Moodley Inc.
  • Pretoria, South Africa, 0002
    • Medical Oncology 2nd Floor Radiotherapy building Steve Biko Academic Hospital
  • Pretoria, South Africa, 0002
    • Pretoria Academic Hospital, Department of Radiation Oncology
• Spain
  • A Coruna, Spain, 15006
    • Complexo Hospitalario a Coruna
  • A Coruña, Spain, 15706
    • Hospital Clinico Universitario de Santiago
  • Badalona, Spain, 08918
    • ICO Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08007
    • Hospital Duran i Reinals
  • El Palmar, Spain, 30120
    • Hospital Universitario Virgen de la Arrixaca
  • Madrid, Spain, CP 28007
    • Hospital General Universitario Gregorio Marañon
  • Murcia, Spain, 30008
    • Hospital Universitario Morales Meseguer
  • Oviedo, Spain, 33006
    • Hospital Universitario Central de Asturias
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James's Institute of Oncology Bexley Wing
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • London, United Kingdom, EC1A 7BE
    • Institute of Cancer/ Centre for Medical Oncology/Barts and The London School of Medicine and Dentistry
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust, The Christie Hospital,
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Northern Centre for Cancer Care, Freeman Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Haemato-Oncology Wards
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • La Verne, California, United States, 91750
      • Wilshire Oncology Medical Group, Inc
    • Palm Springs, California, United States, 92262
      • Comprehensive Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center-Section of Medical Oncology
    • Trumbull, Connecticut, United States, 06611
      • Oncology Associates of Bridgeport
  • Florida
    • Boca Raton, Florida, United States, 33432
      • Boca Raton Clinical Research Associates
  • Georgia
    • Augusta, Georgia, United States, 30912-3125
      • Georgia Health Sciences University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Evanston, Illinois, United States, 60201
      • Kellogg Cancer Care Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists/Cancer Care & Hematology Specialists of Chicagoland
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare, P.C.
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancers and Blood Disorders
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northern New Jersey Cancer Associates
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital
  • New York
    • Bronx, New York, United States, 10467
      • Bronx River Medical Associates, PC
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center (Roswell Park)
    • Lake Success, New York, United States, 11067
      • Monter Cancer Center
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • New York University
    • New York, New York, United States, 10016
      • New York University Cancer Institute
    • Syracuse, New York, United States, 13210
      • Upstate Medical Univeristy Syracuse
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Bedford, Ohio, United States, 44146
      • Hematology Associates
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St Luke's Cancer Center
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Cancer Institute
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Associates in Oncology and Hematology
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Cancer Institute
    • Memphis, Tennessee, United States, 38138
      • Accelerated Community Oncology Reseaerch Network, Inc. (ACORN)
  • Texas
    • Houston, Texas, United States, 77030
      • UT - M. D. Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • The UT Health Science Centre at San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298-0035
      • Massey Cancer Center
  • Washington
    • Kirkland, Washington, United States, 98304
      • Cascade Cancer Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center - Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• A histologically confirmed diagnosis of PTCL
• Participants must have relapsed or refractory disease after at least one prior systemic anticancer regimen. Systemic anticancer therapy is defined as chemotherapy or immunotherapy administered systemically.
• Participants must have at least one site of disease measurable in two dimensions by computed tomography (CT).
• Age ≥ 18 years.
• Adequate bone marrow, liver, and renal functions.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Negative pregnancy test for women of childbearing potential.

Exclusion criteria:

• Relapse within 100 days of autologous or allogeneic bone marrow transplant.
• Prior histone deacetylase (HDAC) inhibitor therapy.
• Co-existing active infection or any medical condition likely to interfere with trial procedures.
• Severe cardiovascular disease.
• Clinically significant central nervous system disorders with altered mental status or psychiatric disorders precluding understanding of the informed consent process and/or completion of the necessary studies.
• Active concurrent malignancy (except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix).
• Symptomatic or untreated central nervous system (CNS) metastases.
• Pregnant or breast-feeding women.
• Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Belinostat; Belinostat 1000 mg/m^2 administered as a 30 minute IV infusion on Days 1-5 of every 3-week cycle until disease progression or unmanageable treatment-related toxicities.	Drug: Belinostat; Other Names: PXD101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to International Working Group (IWG) criteria. The response was assessed based on clinical and radiological criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites. As pre-defined, the primary endpoint analysis for this study was based on the Independent Review Committee (IRC) assessment of response.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Response	Time to response was defined as the time (in weeks) from first administration of treatment until first response. Response is defined as complete response (CR) or partial response (PR). CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites.	24 months
Duration of Response	The Duration of Response was assessed by IWG criteria per the IRC from the date the measurement criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that relapse or progression was documented. It was estimated by the Kaplan-Meier method. Response is defined as complete response (CR) or partial response (PR). CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites.	24 months
Time to Progression	Time to progression was defined as the time (in months) from first administration of treatment to the date of disease progression based on tumor assessments made according to the IWG criteria as assessed by the IRC. The progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.	24 months
Progression Free Survival	Progression-free survival (PFS) was the duration of time from first administration of study treatment to date of first documented progression or death from any cause. It was based on tumor assessments made according to the IWG criteria as assessed by the IRC. The progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.	24 months
Overall Survival	Overall Survival was the time from first administration of study treatment until the date of death.	24 months
Number of Participants With At Least One Serious Treatment-Emergent Adverse Event (TEAE)	A TEAE was defined as an event with an onset date and time on or after the first dosing start date and time, or on or after the first dosing start date if the onset time was missing. A serious TEAE was any untoward medical occurrence that at any dose results in death, prolonged hospitalization, persistent or significant disability or congenital abnormalities.	24 months

Other Outcome Measures

Outcome Measure	Time Frame
Population Pharmacokinetics	24 months

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc
• Collaborators: Onxeo
• Investigators: Principal Investigator: Peter Brown, MD, H:S Rigshospitalet, Department of Hematology, Denmark; Principal Investigator: Pier L Zinzani, MD, Università di Bologna, Italy; Principal Investigator: André Bosly, MD, Cliniques Universitaires UCL Mont Godinne, Belgium; Principal Investigator: Georges Fillet, MD, University of Liège, Belgium; Principal Investigator: Eric van den Neste, MD, Clinique Universitaier Saint Luc, Belgium; Principal Investigator: Nicolas Monier, MD, Hôpital de l'Archet 1 Centre Hospitalier Universitaire (CHU) de Nice, France; Principal Investigator: Elisabeth Perez, MD, Groupe Hospitalier Sud Réunion, France; Principal Investigator: Maria Delioukina, MD, City of Hope National Medical Center, USA; Principal Investigator: Adam Lerner, MD, Boston Medical Center, USA; Principal Investigator: Lydia Dreosti, MD, Pretoria Academic Hospital, South Africa; Principal Investigator: D. Moodley, MD, Drs Pirjol, Szpak and Moodley Inc, Durban, South Africa; Principal Investigator: Hanneke C. Kluin-Nelemans, MD, University Medical Center Groningen UMCG, The Netherlands; Principal Investigator: G. Sissolak, MD, Tygerberg Hospital, Cape Town, South Africa; Principal Investigator: L. Verdonk, MD, Isala Clinics, Zwolle, The Netherlands; Principal Investigator: O. Visser, MD, VU Medical Center, Amsterdam, The Netherlands; Principal Investigator: Owen A. O'Connor, MD, New York University Cancer Institute, USA; Principal Investigator: Sarit Assouline, MD, McGill University, Department of Oncology Clinical Research Program, Montreal, Canada; Principal Investigator: Juan Manuel Sancho Cia, MD, ICO Hospital Germans Trias i Pujol, Badalona, Spain; Principal Investigator: Consolación Rayon, MD, Hospital Universitario Central de Asturias, Oviedo, Spain; Principal Investigator: Sonia Gonzales, MD, Hospital Clinico Universitario de Santiago, Santiago de Compostella, Spain; Principal Investigator: Lorenz Trümper, MD, Universität Göttingen, Abteilung Hämatologie und Onkologie, Göttingen, Germany; Principal Investigator: Andreas Viardot, MD, Universitätsklinikum Ulm, Ulm, Germany; Principal Investigator: Georg Hess, MD, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany; Principal Investigator: Hans-Heinrich Wolf, MD, Universitätsklinikum (AöR) der Martin-Luther-Universität Halle-Wittenberg, Halle, Germany; Principal Investigator: Andreas Neubauer, MD, University Hospital Marburg, Marburg, Germany; Principal Investigator: Michele Frank, MD, Cascade Cancer Center; Principal Investigator: Madeleine Duvic, MD, UT - M. D. Anderson Cancer Center; Principal Investigator: Andrei Shustov, MD, Fred Hutchinson Cancer Research Center - Seattle Cancer Care Alliance; Principal Investigator: Melissa Runge-Morris, MD, Barbara Ann Karmanos Cancer Institute; Principal Investigator: Nalini Janakiraman, MD, Henry Ford Health System; Principal Investigator: Amanda Cashen, MD, Wasington University School of Medicine- Division of Oncology; Principal Investigator: Mohammad Tirgan, MD, Hematology Associates; Principal Investigator: Bernard Poiesz, MD, Upstate Medical Univeristy Syracuse; Principal Investigator: Charles Farber, MD, Morristown Memorial Hospital; Principal Investigator: Zale Bernstein, MD, Erie County Medical Center (Roswell Park); Principal Investigator: Ralph Boccia, MD, Center for Cancers and Blood Disorders; Principal Investigator: David Grinblatt, MD, Kellogg Cancer Care Center; Principal Investigator: Laura Blakely, MD, Accelerated Community Oncology Reseaerch Network, Inc. (ACORN); Principal Investigator: David Dennis, MD, Boca Raton Clinical Research Associates; Principal Investigator: Fernando Camacho, MD, Bronx River Medical Associates, PC; Principal Investigator: Eliot Epner, MD, Penn State Hershey Cancer Institute

Publications and helpful links

General Publications

• Campbell P, Thomas CM. Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. J Oncol Pharm Pract. 2017 Mar;23(2):143-147. doi: 10.1177/1078155216634178. Epub 2016 Jun 23.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2008
• Primary Completion (ACTUAL): November 5, 2013
• Study Completion (ACTUAL): October 27, 2014

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (ESTIMATE): March 20, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: PTCL; HDAC inhibitor; Histone deacetylase inhibitor; Peripheral T-cell lymphoma; Belinostat; PXD101
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Belinostat
• Other Study ID Numbers: PXD101-CLN-19; 2008-005843-40 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No