Efficacy and Safety of Romidepsin CHOP vs CHOP in Patients With Untreated Peripheral T-Cell Lymphoma

January 9, 2023 updated by: The Lymphoma Academic Research Organisation

Phase 3 Multi-center Randomized Study to Compare Efficacy and Safety of Romidepsin CHOP (Ro-CHOP) Versus CHOP in Patients With Previously Untreated Peripheral T-cell Lymphoma

Primary objective of the study is to compare the efficacy of romidepsin when administered with CHOP versus CHOP alone in subjects with previously untreated peripheral T-cell lymphoma (PTCL) in terms of progression-free survival (PFS) assessed according to Response criteria for malignant lymphoma 1999 by a Response Adjudication Committee (RAC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized multi-center phase III study, to compare efficacy and safety of Ro-CHOP with standard CHOP regimen in patients with previously untreated, histologically proven PTCL. Given the nature of the experimental agent, this study is an open-label study. Patients are randomized 1:1 to receive either (Arm A) cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles [22] or (Arm B) romidepsin CHOP (Ro-CHOP) administered in 3 week cycles for 6 cycles. In the Ro-CHOP arm, romidepsin will be administered at a dose of 12 mg/m² IV on day 1 and day 8 every 3 weeks. In this study, patients will advance through three phases of the study: screening phase, treatment phase and follow-up phase. Patients will receive study drug(s) for up to 6 cycles, or until unacceptable toxicity will develop or progression or voluntary withdrawal. Patients will be followed for survival until the earliest of either 80% of patients have died or 3 years from the last patient randomized. Three years after the primary analysis an update of the database will be done and a rerun of the analysis will be performed.

Study Type

Interventional

Enrollment (Actual)

421

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium
        • ZNA Stuivenberg
      • Brugge, Belgium
        • A.Z. Sint Jan AV
      • Bruxelles, Belgium
        • Institut Jules Bordet
      • Bruxelles, Belgium
        • UCL Louvain Saint Luc
      • Bruxelles, Belgium
        • ULB - Hôpital Erasme
      • Charleroi, Belgium
        • Grand Hopital De Charleroi
      • Haine Saint Paul, Belgium
        • Hopital Jolimont
      • Jette, Belgium
        • AZ VUB
      • Kortrijk, Belgium
        • AZ Groeninge
      • Liege, Belgium
        • CHU de Liège
      • Liege, Belgium
        • CHC - Clinique Saint Joseph
      • Yvoir, Belgium
        • Chu Mont Godinne
  • France
      • Amiens, France
        • CHU D'amiens
      • Angers, France
        • CHU d'Angers
      • Annecy, France
        • CH de Annecy
      • Avignon, France
        • CH Henri Duffaut
      • Bayonne, France
        • CH Côte Basque
      • Besançon, France
        • Chu Jean Minjoz
      • Bordeaux, France
        • Institut Bergonié
      • Bordeaux, France
        • Polyclinique Bordeaux Nord Aquitaine
      • Bordeaux, France
        • CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
      • Boulogne-sur-mer, France
        • CH du Dr Duchenne
      • Bourg en Bresse, France
        • CH de Bourg en Bresse
      • Béziers, France
        • CH de Béziers
      • Caen, France
        • Centre Francois Baclesse
      • Caen, France
        • Institut d'Hematologie de Basse-Normandie
      • Chalon sur Saône, France
        • CH de Chalon sur Saone
      • Chambéry, France
        • Ch De Chambery
      • Clamart, France
        • Hôpital Antoine Béclère
      • Clermont-Ferrand, France
        • CHU Estaing
      • Colmar, France
        • Hôpital Pasteur
      • Corbeil Essonnes, France
        • CH Sud Francilien de Corbeil
      • Créteil, France
        • Chu Henri Mondor
      • Dijon, France
        • Chu de Dijon
      • Dunkerque, France
        • CH de Dunkerque
      • Grenoble, France
        • Chu de Grenoble
      • La Roche sur Yon, France
        • CHD La Roche sur Yon
      • Le Chesnay, France, 78157
        • Centre Hospitalier de Versailles - André Mignot
      • Le Kremlin Bicêtre, France
        • Hôpital Kremlin Bicêtre
      • Le Mans, France
        • CH du Mans
      • Le Mans, France
        • Clinique Victor Hugo
      • Lens, France
        • CH de Lens
      • Lille, France, 59037
        • CHRU de Lille - Hôpital Claude Hurriez
      • Lille, France
        • Hôpital Saint Vincent de Paul
      • Lille, France
        • CH de Saint Quentin
      • Limoges, France
        • CHU de Limoges
      • Lyon, France
        • Centre Leon Berard
      • Mantes-La-Jolie, France
        • CH de Saint Germain
      • Mantes-la-Jolie, France
        • Chi Poissy /Saint- Germain-En-Laye
      • Marseille, France
        • Institut Paoli Calmettes
      • Meaux, France
        • CH de Meaux
      • Metz, France
        • CHR de Metz
      • Montpellier, France
        • Hopital Saint Eloi
      • Mulhouse, France
        • CHU de Mulhouse
      • Nancy, France
        • CHU Nancy Brabois
      • Nantes, France
        • CHU Hotel Dieu Nantes
      • Nice, France
        • Centre Antoine Lacassagne
      • Nice, France
        • CHU de Nice
      • Nimes, France
        • CHU de Nimes - Caremeau
      • Paris, France, 75743
        • Hopital Necker
      • Paris, France
        • Hopital de La Pitie Salpetriere
      • Paris, France
        • Hôpital Saint Antoine
      • Paris, France
        • Hopital Saint Louis
      • Paris, France
        • Institut Curie
      • Perpignan, France
        • CH de Perpignan
      • Pessac, France
        • Centre Francois Magendie
      • Pierre Bénite, France, 69495
        • Centre Hospitalier Lyon Sud
      • Poitiers, France
        • Chu de Poitiers
      • Reims, France
        • CHU Robert Debré
      • Rennes, France
        • Chu Pontchaillou
      • Roubaix, France
        • CH de Roubaix
      • Rouen, France
        • Centre Henri Becquerel
      • Saint Cloud, France
        • Institut Curie - Centre Rene Huguenin
      • Toulouse, France
        • CHU de Toulouse
      • Tours, France, 37044
        • Chu Bretonneau
      • Valence, France
        • CH Valence
      • Valenciennes, France
        • Ch de Valenciennes
      • Vannes, France
        • Ch de Bretagne Atlantique
      • Villejuif, France
        • Institut Gustave Roussy
  • Germany
      • Berlin, Germany
        • Vivantes Klinikum Neukölln
      • Berlin, Germany
        • Charité Medical School Campus Benjamin Franklin
      • Berlin, Germany
        • Charité Medical School Campus Virchow-Klinikum
      • Berlin, Germany
        • Helios Hospital Berlin-Buch
      • Dortmund, Germany
        • St Johannes-Hospital
      • Dresden, Germany
        • Universitätsklinikum Carl Gustav Carus der TU Dresden
      • Düsseldorf, Germany
        • Klinik Universitätsklinikum Düsseldorf
      • Essen, Germany
        • University of Duisburg-Essen
      • Frankfurt am Main, Germany
        • Krankenhaus Nordwest
      • Freiburg, Germany
        • Universitätklinikum Freiburg Klinik für Innere medizin I
      • Greifswald, Germany
        • Universitätsmedizin Greifswald
      • Göttingen, Germany
        • UniversitätsKrebszentrum Göttingen - G-CCC
      • Hamburg, Germany
        • Asklepios Klinik St. Georg
      • Homburg, Germany
        • Universitätsklinikum des Saarlandes
      • Köln, Germany
        • Uniklinik Koln
      • Leipzig, Germany
        • Klinikum St. Georg gGmbH
      • Oldenburg, Germany
        • Klinikum Oldenburg gGmbH
      • Ulm, Germany
        • Universitatsklinikum Ulm
  • Italy
      • Bologna, Italy
        • Istituto di Ematologia "Saragnoli" Policlinico San'Orsola-Malpighi, Bologna
      • Brescia, Italy
        • Azienda Ospedaliera Spedali Civili di Brescia
      • Catania, Italy
        • Ospedale Ferrarotto
      • Cuneo, Italy
        • Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo
      • Firenze, Italy
        • Azienda Ospedaliera Universitaria Careggi
      • Napoli, Italy
        • Ematologia Oncologica Istituto Pascale
      • Reggio Calabria, Italy
        • Azienda Ospedaliera Bianchi Melacrino Morelli
      • Roma, Italy
        • Ematologia Università La Sapienza
      • Torino, Italy
        • AOU San Giovanni Battista
      • Udine, Italy
        • Clinica Ematologica di Udine
  • Korea, Republic of
      • Busan, Korea, Republic of
        • Dong-A Univ. Hospital
      • Goyang-si, Korea, Republic of
        • National Cancer Center
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • Asian Medical Center
      • Seoul, Korea, Republic of
        • Korean Cancer Center Hospital
      • Seoul, Korea, Republic of
        • Severance Hospital Yonsei University
  • Portugal
      • Lisbon, Portugal
        • Instituto Português Oncologia
  • Singapore
      • Singapore, Singapore
        • Singapore General Hospital
      • Singapore, Singapore
        • National Cancer Centre Singapore
      • Singapore, Singapore
        • National University Cancer Hospital
  • Spain
      • Barcelona, Spain
        • Hospital Clinic De Barcelona
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • ICO L'Hospitalet
      • Barcelone, Spain
        • Hospital De La Santa Creu I Sant Pau
      • Girona, Spain
        • ICO - Institut Català d'Oncologia - Hospital Doctor Josep Trueta
      • Jerez de la Frontera, Spain
        • Hospital de Jerez de la Frontera
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Murcia, Spain
        • H. Morales Messeguer
      • Oviedo, Spain
        • Hospital Universitario Central de Asturias
      • Salamanca, Spain
        • Hospital Clínico Universitario de Salamanca
      • Sevilla, Spain
        • H. Virgen del Rocío
      • Valencia, Spain
        • Hospital Arnau de Vilanova de Valencia
      • Valencia, Spain
        • Hospital Universitario Dr. Peset de Valencia
      • Valladolid, Spain
        • Hospital Clinico Universitario de Valladolid

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Males and females of 18 years of age to 80 years of age.
  2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
  3. Able to adhere to the study visit schedule and other protocol requirements.

  4. Patients with histologically proven peripheral T-cell lymphoma (PTCL), not previously treated; the following subtypes as defined by the World Health Organization (WHO) classification (2008;2011) may be included, whatever the Ann Arbor stage (I - IV):

    a. Nodal types: i. PTCL, not otherwise specified ii. Angioimmunoblastic T-cell lymphoma iii. Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK)-negative type

    b. Extra-nodal types: i. Enteropathy-associated T-cell lymphoma ii. Hepato-splenic T-cell lymphoma iii. Subcutaneous panniculitis-like T-cell lymphoma iv. Primary cutaneous gamma-delta T-cell lymphoma v. Primary cutaneous cluster of differentiation 8 positive (CD8+) aggressive epidermotropic lymphoma vi. Primary cutaneous cluster of differentiation 4 positive (CD4+) small/medium T-cell lymphoma

    c. Other non classifiable peripheral T-cell lymphoma

  5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  6. Negative pregnancy test for Females of ChildBearing Potential (FCBP)
  7. Female patients of child bearing potential must use an effective method of birth control (i.e. hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide or abstinence) during treatment period and 1 month thereafter; Males must use an effective method of birth control during treatment period and 3 months thereafter.
  8. Life expectancy of ≥ 90 days (3 months).

Exclusion Criteria:

  1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
  2. Any condition that confounds the ability to interpret data from the study.
  3. Other types of lymphomas, e.g. B-cell lymphoma

  4. The following types of T cell lymphomas:

    1. Adult T-cell lymphoma/leukemia (HTLV-1 related T-cell lymphoma)
    2. Extranodal T-cell/Natural Killer (NK)-cell lymphoma, nasal type
    3. Anaplastic large cell lymphoma, ALK-positive type
    4. Cutaneous T cell lymphoma (mycosis fungoid, Sézary syndrome)
    5. Primary cutaneous cluster of differentiation antigen 30 positive (CD30+) T-cell lymphoproliferative disorder
    6. Primary cutaneous anaplastic T-cell lymphoma
  5. Previous treatment for PTCL with immunotherapy or chemotherapy except for short-term corticosteroids (duration of ≤ 8 days) before randomization
  6. Previous radiotherapy for PTCL except if localized to one lymph node area
  7. Patients planned for autologous or allogeneic transplant as consolidation in first line
  8. Central nervous system -meningeal involvement
  9. Contraindication to any drug contained in the chemotherapy regimen,
  10. Subjects with HIV positivity
  11. Subjects with active hepatitis B or C. Chronic carriers of Hepatitis B virus (HBV) without HBV DNA positive blood are eligible. Subjects with non-active hepatitis C (with normal transaminases) are eligible.

  12. Any of the following laboratory abnormalities, except if secondary to the lymphoma:

    1. Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L),
    2. Platelet count < 100,000/mm3 (100 x 109/L), or < 75,000/mm3 if bone marrow is involved,
    3. Serum Aspartate Aminotransferase (ASAT/AST) or Alanine Aminotransferase (ALAT/ALT) ≥ 3.0 x Upper Limit of Normal (ULN),
    4. Serum total bilirubin > 2 x ULN, except in case of hemolytic anemia,
    5. K+ and Mg2+ levels < Lower Limit of Normal (LLN), except if corrected per protocol guidance before beginning the romidepsin infusion
  13. Serum creatinine > 2.0 x ULN
  14. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast or untreated prostatic cancer without any plan for a treatment) unless the patient has been free of the disease for ≥ 3 years
  15. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form

  16. Any known cardiac abnormalities such as:

    1. Patients with congenital long QT syndrome
    2. Corrected QT interval > 480 msec (using the Fridericia formula)
    3. Myocardial infarction within 6 months of cycle 1 day 1
    4. History of or concomitant significant cardiovascular disease
    5. Ejection fraction <45% by multigated acquisition (MUGA) scan or by echocardiogram;
  17. Concomitant use of drugs that may cause a significant prolongation of the corrected QT interval (QTc)
  18. Patients who have received more than 200 mg/m2 doxorubicin
  19. Concomitant use of strong CYP3A4 inhibitors
  20. Concomitant use of therapeutic warfarin due to a potential drug interaction. Use of a low dose of warfarin or another anticoagulant to maintain patency of venous access port and cannulas is permitted.
  21. Clinically significant active infection
  22. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug
  23. Pregnant or lactating females or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental: Romidepsin plus CHOP

Patients in experimental arm receive romidepsin plus CHOP (Ro-CHOP) administered in 3 week cycles for 6 cycles.

Romidepsin is administered at a dose of 12 mg/m² IV on day 1 and day 8 every 3 weeks.
Drug: Romidepsin + CHOP
Ro-CHOP administered in 3 week cycles for 6 cycles or until progression Romidepsin is administered at a dose of 12 mg/m² IV on day 1 and day 8 every 3 weeks.
Active Comparator: Standard: CHOP
Patients in control Arm receive cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles.
Drug: CHOP
CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary efficacy endpoint is Progression Free Survival
Time Frame: 60 months
The primary efficacy endpoint is Progression Free Survival (PFS) using the response criteria for malignant lymphoma (1999) by a Response Adjudication Committee
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Lymphoma Academic Research Organisation

Investigators

  • Study Chair: Emmanuel BACHY, Professor, CH Lyon Sud, Pierre Bénite, France
  • Study Chair: Vincent CAMUS, MD, Centre Henri Becquerel, Rouen, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2013

Primary Completion (Actual)

December 13, 2019

Study Completion (Actual)

December 13, 2022

Study Registration Dates

First Submitted

January 31, 2013

First Submitted That Met QC Criteria

February 20, 2013

First Posted (Estimate)

February 21, 2013

Study Record Updates

Last Update Posted (Estimate)

January 10, 2023

Last Update Submitted That Met QC Criteria

January 9, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ro-CHOP Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Peripheral T-cell Lymphoma

Clinical Trials on Romidepsin + CHOP

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Canada

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe