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

Peripheral T-cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01796002
• Other study ID #: Ro-CHOP Study
• Status: Completed
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: December 13, 2022

Study information

• Verified date: January 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 421
• Est. completion date: December 13, 2022
• Est. primary completion date: December 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-cell Lymphoma

Intervention

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

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	A.Z. Sint Jan AV	Brugge
Belgium	Institut Jules Bordet	Bruxelles
Belgium	UCL Louvain Saint Luc	Bruxelles
Belgium	ULB - Hôpital Erasme	Bruxelles
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	Liege
Belgium	CHU de Liege	Liege
Belgium	CHU Mont Godinne	Yvoir
France	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	Dunkerque
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	CH de Saint Quentin	Lille
France	CHRU de Lille - Hôpital Claude Hurriez	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	Nimes
France	Hôpital de la Pitié Salpétrière	Paris
France	Hôpital Necker	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
Germany	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	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
Germany	UniversitätsKrebszentrum Göttingen - G-CCC	Göttingen
Germany	Universitätsmedizin Greifswald	Greifswald
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitätsklinikum des Saarlandes	Homburg
Germany	Uniklinik Köln	Köln
Germany	Klinikum St. Georg gGmbH	Leipzig
Germany	Klinikum Oldenburg gGmbH	Oldenburg
Germany	Universitätsklinikum Ulm	Ulm
Italy	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	Firenze
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
Korea, Republic of	Dong-A Univ. Hospital	Busan
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asian Medical Center	Seoul
Korea, Republic of	Korean Cancer Center Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University	Seoul
Portugal	Instituto Português Oncologia	Lisbon
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Cancer Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	ICO l'Hospitalet	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelone
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	Sevilla
Spain	Hospital Arnau de Vilanova de Valencia	Valencia
Spain	Hospital Universitario Dr. Peset de Valencia	Valencia
Spain	Hospital Clinico Universitario de Valladolid	Valladolid

Sponsors (1)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Portugal,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary efficacy endpoint is Progression Free Survival	The primary efficacy endpoint is Progression Free Survival (PFS) using the response criteria for malignant lymphoma (1999) by a Response Adjudication Committee	60 months

External Links

•   Drug Information available for: Romidepsin
•   MedlinePlus related topics: Lymphoma