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

Sponsor

The Lymphoma Academic Research Organisation (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01796002

Collaborator

(none)

421

Enrollment

131

Locations

Arms

119.4

Anticipated Duration (Months)

3.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Peripheral T-cell Lymphoma	Drug: Romidepsin + CHOP Drug: CHOP	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

421 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Dec 13, 2019

Anticipated Study Completion Date :

Dec 13, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

The primary efficacy endpoint is Progression Free Survival [60 months]
The primary efficacy endpoint is Progression Free Survival (PFS) using the response criteria for malignant lymphoma (1999) by a Response Adjudication Committee

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Negative pregnancy test for Females of ChildBearing Potential (FCBP)
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.
Life expectancy of ≥ 90 days (3 months).

Exclusion Criteria:

Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
Any condition that confounds the ability to interpret data from the study.
Other types of lymphomas, e.g. B-cell lymphoma
The following types of T cell lymphomas:
Adult T-cell lymphoma/leukemia (HTLV-1 related T-cell lymphoma)
Extranodal T-cell/Natural Killer (NK)-cell lymphoma, nasal type
Anaplastic large cell lymphoma, ALK-positive type
Cutaneous T cell lymphoma (mycosis fungoid, Sézary syndrome)
Primary cutaneous cluster of differentiation antigen 30 positive (CD30+) T-cell lymphoproliferative disorder
Primary cutaneous anaplastic T-cell lymphoma
Previous treatment for PTCL with immunotherapy or chemotherapy except for short-term corticosteroids (duration of ≤ 8 days) before randomization
Previous radiotherapy for PTCL except if localized to one lymph node area
Patients planned for autologous or allogeneic transplant as consolidation in first line
Central nervous system -meningeal involvement
Contraindication to any drug contained in the chemotherapy regimen,
Subjects with HIV positivity
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.
Any of the following laboratory abnormalities, except if secondary to the lymphoma:
Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L),
Platelet count < 100,000/mm3 (100 x 109/L), or < 75,000/mm3 if bone marrow is involved,
Serum Aspartate Aminotransferase (ASAT/AST) or Alanine Aminotransferase (ALAT/ALT) ≥ 3.0 x Upper Limit of Normal (ULN),
Serum total bilirubin > 2 x ULN, except in case of hemolytic anemia,
K+ and Mg2+ levels < Lower Limit of Normal (LLN), except if corrected per protocol guidance before beginning the romidepsin infusion
Serum creatinine > 2.0 x ULN
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
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
Any known cardiac abnormalities such as:
Patients with congenital long QT syndrome
Corrected QT interval > 480 msec (using the Fridericia formula)
Myocardial infarction within 6 months of cycle 1 day 1
History of or concomitant significant cardiovascular disease
Ejection fraction <45% by multigated acquisition (MUGA) scan or by echocardiogram;
Concomitant use of drugs that may cause a significant prolongation of the corrected QT interval (QTc)
Patients who have received more than 200 mg/m2 doxorubicin
Concomitant use of strong CYP3A4 inhibitors
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.
Clinically significant active infection
Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	ZNA Stuivenberg	Antwerpen	Belgium
2	A.Z. Sint Jan AV	Brugge	Belgium
3	Institut Jules Bordet	Bruxelles	Belgium
4	UCL Louvain Saint Luc	Bruxelles	Belgium
5	ULB - Hôpital Erasme	Bruxelles	Belgium
6	Grand Hôpital de Charleroi	Charleroi	Belgium
7	Hôpital Jolimont	Haine Saint Paul	Belgium
8	AZ VUB	Jette	Belgium
9	AZ Groeninge	Kortrijk	Belgium
10	CHC - Clinique Saint Joseph	Liege	Belgium
11	CHU de Liege	Liege	Belgium
12	CHU Mont Godinne	Yvoir	Belgium
13	CHU d'Amiens	Amiens	France
14	CHU d'Angers	Angers	France
15	CH de Annecy	Annecy	France
16	CH Henri Duffaut	Avignon	France
17	CH Côte Basque	Bayonne	France
18	CHU Jean Minjoz	Besançon	France
19	CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie	Bordeaux	France
20	Institut Bergonié	Bordeaux	France
21	Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France
22	CH du Dr Duchenne	Boulogne-sur-mer	France
23	CH de Bourg en Bresse	Bourg en Bresse	France
24	CH de Béziers	Béziers	France
25	Centre François Baclesse	Caen	France
26	Institut d'Hématologie de Basse-Normandie	Caen	France
27	CH de Chalon sur Saône	Chalon sur Saône	France
28	CH de Chambéry	Chambéry	France
29	Hôpital Antoine Béclère	Clamart	France
30	CHU Estaing	Clermont-Ferrand	France
31	Hôpital Pasteur	Colmar	France
32	CH Sud Francilien de Corbeil	Corbeil Essonnes	France
33	CHU Henri Mondor	Créteil	France
34	CHU de Dijon	Dijon	France
35	CH de Dunkerque	Dunkerque	France
36	CHU de Grenoble	Grenoble	France
37	CHD La Roche sur Yon	La Roche sur Yon	France
38	Centre Hospitalier de Versailles - André Mignot	Le Chesnay	France	78157
39	Hôpital Kremlin Bicêtre	Le Kremlin Bicêtre	France
40	CH du Mans	Le Mans	France
41	Clinique Victor Hugo	Le Mans	France
42	CH de Lens	Lens	France
43	CHRU de Lille - Hôpital Claude Hurriez	Lille	France	59037
44	CH de Saint Quentin	Lille	France
45	Hôpital Saint Vincent de Paul	Lille	France
46	CHU de Limoges	Limoges	France
47	Centre Léon Bérard	Lyon	France
48	CH de Saint Germain	Mantes-La-Jolie	France
49	Chi Poissy /Saint- Germain-En-Laye	Mantes-la-Jolie	France
50	Institut Paoli Calmettes	Marseille	France
51	CH de Meaux	Meaux	France
52	CHR de Metz	Metz	France
53	Hôpital Saint Eloi	Montpellier	France
54	CHU de Mulhouse	Mulhouse	France
55	CHU Nancy Brabois	Nancy	France
56	CHU Hôtel Dieu Nantes	Nantes	France
57	Centre Antoine Lacassagne	Nice	France
58	CHU de Nice	Nice	France
59	CHU de Nîmes - Caremeau	Nimes	France
60	Hôpital Necker	Paris	France	75743
61	Hôpital de la Pitié Salpétrière	Paris	France
62	Hôpital Saint Antoine	Paris	France
63	Hôpital Saint Louis	Paris	France
64	Institut Curie	Paris	France
65	CH de Perpignan	Perpignan	France
66	Centre François Magendie	Pessac	France
67	Centre Hospitalier Lyon Sud	Pierre Bénite	France	69495
68	CHU de Poitiers	Poitiers	France
69	CHU Robert Debré	Reims	France
70	CHU Pontchaillou	Rennes	France
71	CH de Roubaix	Roubaix	France
72	Centre Henri Becquerel	Rouen	France
73	Institut Curie - Centre René Huguenin	Saint Cloud	France
74	CHU de Toulouse	Toulouse	France
75	CHU Bretonneau	Tours	France	37044
76	CH Valence	Valence	France
77	CH de Valenciennes	Valenciennes	France
78	CH de Bretagne Atlantique	Vannes	France
79	Institut Gustave Roussy	Villejuif	France
80	Charité Medical School Campus Benjamin Franklin	Berlin	Germany
81	Charité Medical School Campus Virchow-Klinikum	Berlin	Germany
82	HELIOS Hospital Berlin-Buch	Berlin	Germany
83	Vivantes Klinikum Neukölln	Berlin	Germany
84	St Johannes-Hospital	Dortmund	Germany
85	Universitätsklinikum Carl Gustav Carus der TU Dresden	Dresden	Germany
86	Klinik Universitätsklinikum Düsseldorf	Düsseldorf	Germany
87	University of Duisburg-Essen	Essen	Germany
88	Krankenhaus Nordwest	Frankfurt am Main	Germany
89	Universitätklinikum Freiburg Klinik für Innere medizin I	Freiburg	Germany
90	Universitätsmedizin Greifswald	Greifswald	Germany
91	UniversitätsKrebszentrum Göttingen - G-CCC	Göttingen	Germany
92	Asklepios Klinik St. Georg	Hamburg	Germany
93	Universitätsklinikum des Saarlandes	Homburg	Germany
94	Uniklinik Köln	Köln	Germany
95	Klinikum St. Georg gGmbH	Leipzig	Germany
96	Klinikum Oldenburg gGmbH	Oldenburg	Germany
97	Universitätsklinikum Ulm	Ulm	Germany
98	Istituto di Ematologia "Saragnoli" Policlinico San'Orsola-Malpighi, Bologna	Bologna	Italy
99	Azienda Ospedaliera Spedali Civili di Brescia	Brescia	Italy
100	Ospedale Ferrarotto	Catania	Italy
101	Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo	Cuneo	Italy
102	Azienda Ospedaliera universitaria Careggi	Firenze	Italy
103	Ematologia Oncologica Istituto Pascale	Napoli	Italy
104	Azienda Ospedaliera Bianchi Melacrino Morelli	Reggio Calabria	Italy
105	Ematologia Università La Sapienza	Roma	Italy
106	AOU San Giovanni Battista	Torino	Italy
107	Clinica Ematologica di Udine	Udine	Italy
108	Dong-A Univ. Hospital	Busan	Korea, Republic of
109	National Cancer Center	Goyang-si	Korea, Republic of
110	Asian Medical Center	Seoul	Korea, Republic of
111	Korean Cancer Center Hospital	Seoul	Korea, Republic of
112	Samsung Medical Center	Seoul	Korea, Republic of
113	Severance Hospital Yonsei University	Seoul	Korea, Republic of
114	Instituto Português Oncologia	Lisbon	Portugal
115	National Cancer Centre Singapore	Singapore	Singapore
116	National University Cancer Hospital	Singapore	Singapore
117	Singapore General Hospital	Singapore	Singapore
118	Hospital Clínic de Barcelona	Barcelona	Spain
119	Hospital del Mar	Barcelona	Spain
120	ICO l'Hospitalet	Barcelona	Spain
121	Hospital de la Santa Creu i Sant Pau	Barcelone	Spain
122	ICO - Institut Català d'Oncologia - Hospital Doctor Josep Trueta	Girona	Spain
123	Hospital de Jerez de la Frontera	Jerez de la Frontera	Spain
124	Hospital Universitario 12 de Octubre	Madrid	Spain
125	H. Morales Messeguer	Murcia	Spain
126	Hospital Universitario Central de Asturias	Oviedo	Spain
127	Hospital Clínico Universitario de Salamanca	Salamanca	Spain
128	H. Virgen del Rocío	Sevilla	Spain
129	Hospital Arnau de Vilanova de Valencia	Valencia	Spain
130	Hospital Universitario Dr. Peset de Valencia	Valencia	Spain
131	Hospital Clinico Universitario de Valladolid	Valladolid	Spain

Sponsors and Collaborators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.

Responsible Party:

The Lymphoma Academic Research Organisation

ClinicalTrials.gov Identifier:

NCT01796002

Other Study ID Numbers:

Ro-CHOP Study

First Posted:

Feb 21, 2013

Last Update Posted:

Aug 19, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by The Lymphoma Academic Research Organisation

PTCL

Additional relevant MeSH terms:

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Romidepsin

Study Results

No Results Posted as of Aug 19, 2022