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

NCT ID: NCT01796002

Last Updated: 2023-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 421 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2022-12-13

Brief Summary

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).

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.

Conditions

Peripheral T-cell Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Romidepsin + CHOP

Intervention Type: DRUG

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.

Standard: CHOP

Patients in control Arm receive cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles.

Group Type: ACTIVE_COMPARATOR

CHOP

Intervention Type: DRUG

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 6 cycles.

Interventions

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.

Intervention Type: DRUG

CHOP

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) administered in 3 week cycles for 6 cycles.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel BACHY, Professor

Role: STUDY_CHAIR

CH Lyon Sud, Pierre Bénite, France

Vincent CAMUS, MD

Role: STUDY_CHAIR

Centre Henri Becquerel, Rouen, France

Locations

ZNA Stuivenberg

Antwerp, , Belgium

A.Z. Sint Jan AV

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

UCL Louvain Saint Luc

Brussels, , Belgium

ULB - Hôpital Erasme

Brussels, , Belgium

Grand Hôpital de Charleroi

Charleroi, , Belgium

Hôpital Jolimont

Haine-Saint-Paul, , Belgium

AZ VUB

Jette, , Belgium

AZ Groeninge

Kortrijk, , Belgium

CHC - Clinique Saint Joseph

Liège, , Belgium

CHU de Liege

Liège, , Belgium

CHU Mont Godinne

Yvoir, , Belgium

CHU d'Amiens

Amiens, , France

CHU d'Angers

Angers, , France

CH de Annecy

Annecy, , France

CH Henri Duffaut

Avignon, , France

CH Côte Basque

Bayonne, , France

CHU Jean Minjoz

Besançon, , France

CH de Béziers

Béziers, , France

CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie

Bordeaux, , France

Institut Bergonié

Bordeaux, , France

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

CH du Dr Duchenne

Boulogne-sur-Mer, , France

CH de Bourg en Bresse

Bourg-en-Bresse, , France

Centre François Baclesse

Caen, , France

Institut d'Hématologie de Basse-Normandie

Caen, , France

CH de Chalon sur Saône

Chalon-sur-Saône, , France

CH de Chambéry

Chambéry, , France

Hôpital Antoine Béclère

Clamart, , France

CHU Estaing

Clermont-Ferrand, , France

Hôpital Pasteur

Colmar, , France

CH Sud Francilien de Corbeil

Corbeil-Essonnes, , France

CHU Henri Mondor

Créteil, , France

CHU de Dijon

Dijon, , France

CH de Dunkerque

Dunkirk, , France

CHU de Grenoble

Grenoble, , France

CHD La Roche sur Yon

La Roche-sur-Yon, , France

Centre Hospitalier de Versailles - André Mignot

Le Chesnay, , France

Hôpital Kremlin Bicêtre

Le Kremlin-Bicêtre, , France

CH du Mans

Le Mans, , France

Clinique Victor Hugo

Le Mans, , France

CH de Lens

Lens, , France

CHRU de Lille - Hôpital Claude Hurriez

Lille, , France

CH de Saint Quentin

Lille, , France

Hôpital Saint Vincent de Paul

Lille, , France

CHU de Limoges

Limoges, , France

Centre Léon Bérard

Lyon, , France

CH de Saint Germain

Mantes-la-Jolie, , France

Chi Poissy /Saint- Germain-En-Laye

Mantes-la-Jolie, , France

Institut Paoli Calmettes

Marseille, , France

CH de Meaux

Meaux, , France

CHR de Metz

Metz, , France

Hôpital Saint Eloi

Montpellier, , France

CHU de Mulhouse

Mulhouse, , France

CHU Nancy Brabois

Nancy, , France

CHU Hôtel Dieu Nantes

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

CHU de Nice

Nice, , France

CHU de Nîmes - Caremeau

Nîmes, , France

Hôpital Necker

Paris, , France

Hôpital de la Pitié Salpétrière

Paris, , France

Hôpital Saint Antoine

Paris, , France

Hôpital Saint Louis

Paris, , France

Institut Curie

Paris, , France

CH de Perpignan

Perpignan, , France

Centre François Magendie

Pessac, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHU de Poitiers

Poitiers, , France

CHU Robert Debré

Reims, , France

CHU Pontchaillou

Rennes, , France

CH de Roubaix

Roubaix, , France

Centre Henri Becquerel

Rouen, , France

Institut Curie - Centre René Huguenin

Saint-Cloud, , France

CHU de Toulouse

Toulouse, , France

CHU Bretonneau

Tours, , France

CH Valence

Valence, , France

CH de Valenciennes

Valenciennes, , France

CH de Bretagne Atlantique

Vannes, , France

Institut Gustave Roussy

Villejuif, , France

Charité Medical School Campus Benjamin Franklin

Berlin, , Germany

Charité Medical School Campus Virchow-Klinikum

Berlin, , Germany

HELIOS Hospital Berlin-Buch

Berlin, , Germany

Vivantes Klinikum Neukölln

Berlin, , Germany

Uniklinik Köln

Cologne, , Germany

St Johannes-Hospital

Dortmund, , Germany

Universitätsklinikum Carl Gustav Carus der TU Dresden

Dresden, , Germany

Klinik Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

University of Duisburg-Essen

Essen, , Germany

Krankenhaus Nordwest

Frankfurt am Main, , Germany

Universitätklinikum Freiburg Klinik für Innere medizin I

Freiburg im Breisgau, , Germany

UniversitätsKrebszentrum Göttingen - G-CCC

Göttingen, , Germany

Universitätsmedizin Greifswald

Greifswald, , Germany

Asklepios Klinik St. Georg

Hamburg, , Germany

Universitätsklinikum des Saarlandes

Homburg, , Germany

Klinikum St. Georg gGmbH

Leipzig, , Germany

Klinikum Oldenburg gGmbH

Oldenburg, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Istituto di Ematologia "Saragnoli" Policlinico San'Orsola-Malpighi, Bologna

Bologna, , Italy

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, , Italy

Ospedale Ferrarotto

Catania, , Italy

Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo

Cuneo, , Italy

Azienda Ospedaliera universitaria Careggi

Florence, , Italy

Ematologia Oncologica Istituto Pascale

Napoli, , Italy

Azienda Ospedaliera Bianchi Melacrino Morelli

Reggio Calabria, , Italy

Ematologia Università La Sapienza

Roma, , Italy

AOU San Giovanni Battista

Torino, , Italy

Clinica Ematologica di Udine

Udine, , Italy

Instituto Português Oncologia

Lisbon, , Portugal

National Cancer Centre Singapore

Singapore, , Singapore

National University Cancer Hospital

Singapore, , Singapore

Singapore General Hospital

Singapore, , Singapore

Dong-A Univ. Hospital

Busan, , South Korea

National Cancer Center

Goyang-si, , South Korea

Asian Medical Center

Seoul, , South Korea

Korean Cancer Center Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Severance Hospital Yonsei University

Seoul, , South Korea

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

ICO l'Hospitalet

Barcelona, , Spain

ICO - Institut Català d'Oncologia - Hospital Doctor Josep Trueta

Girona, , Spain

Hospital de Jerez de la Frontera

Jerez de la Frontera, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

H. Morales Messeguer

Murcia, , Spain

Hospital Universitario Central de Asturias

Oviedo, , Spain

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

H. Virgen del Rocío

Seville, , Spain

Hospital Arnau de Vilanova de Valencia

Valencia, , Spain

Hospital Universitario Dr. Peset de Valencia

Valencia, , Spain

Hospital Clinico Universitario de Valladolid

Valladolid, , Spain

Countries

Belgium; France; Germany; Italy; Portugal; Singapore; South Korea; Spain

References

Camus V, Thieblemont C, Gaulard P, Cheminant M, Casasnovas RO, Ysebaert L, Damaj GL, Guidez S, Pica GM, Kim WS, Lim ST, Andre M, Gutierrez N, Penarrubia MJ, Staber PB, Trotman J, Huttmann A, Stefoni V, Tucci A, Fogarty P, Farhat H, Abraham J, Abarah W, Belmecheri F, Ribrag V, Delfau-Larue MH, Cottereau AS, Itti E, Li J, Delarue R, de Leval L, Morschhauser F, Bachy E. Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial. J Clin Oncol. 2024 May 10;42(14):1612-1618. doi: 10.1200/JCO.23.01687. Epub 2024 Feb 16.

Reference Type: DERIVED

PMID: 38364196 (View on PubMed)

Bachy E, Camus V, Thieblemont C, Sibon D, Casasnovas RO, Ysebaert L, Damaj G, Guidez S, Pica GM, Kim WS, Lim ST, Andre M, Garcia-Sancho AM, Penarrubia MJ, Staber PB, Trotman J, Huttmann A, Stefoni V, Re A, Gaulard P, Delfau-Larue MH, de Leval L, Meignan M, Li J, Morschhauser F, Delarue R. Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA). J Clin Oncol. 2022 Jan 20;40(3):242-251. doi: 10.1200/JCO.21.01815. Epub 2021 Nov 29.

Reference Type: DERIVED

PMID: 34843406 (View on PubMed)

Related Links

http://www.nlm.nih.gov/medlineplus/lymphoma.html

MedlinePlus related topics: Lymphoma

http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=0128517077&QV1=ROMIDEPSIN

Drug Information available for: Romidepsin

Other Identifiers

Ro-CHOP Study

Identifier Type: -

Identifier Source: org_study_id