Clinical trial NCT01796002: Efficacy and Safety of Romidepsin CHOP vs CHOP in Patients With Untreated Peripheral T-Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peripheral T-cell Lymphoma
Keywords: PTCL
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
First posted: 2013-02-21
Enrollment: 421
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The primary efficacy endpoint is Progression Free Survival
timeFrame: 60 months
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Brugge
country: Belgium
facility: A.Z. Sint Jan AV
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: UCL Louvain Saint Luc
city: Bruxelles
country: Belgium
facility: ULB - Hôpital Erasme
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Haine Saint Paul
country: Belgium
facility: Hôpital Jolimont
city: Jette
country: Belgium
facility: AZ VUB
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liege
country: Belgium
facility: CHC - Clinique Saint Joseph
city: Liege
country: Belgium
facility: CHU de Liege
city: Yvoir
country: Belgium
facility: CHU Mont Godinne
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Annecy
country: France
facility: CH de Annecy
city: Avignon
country: France
facility: CH Henri Duffaut
city: Bayonne
country: France
facility: CH Côte Basque
city: Besançon
country: France
facility: CHU Jean Minjoz
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
city: Bordeaux
country: France
facility: Institut Bergonié
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne-sur-mer
country: France
facility: CH du Dr Duchenne
city: Bourg en Bresse
country: France
facility: CH de Bourg en Bresse
city: Béziers
country: France
facility: CH de Béziers
city: Caen
country: France
facility: Centre François Baclesse
city: Caen
country: France
facility: Institut d'Hématologie de Basse-Normandie
city: Chalon sur Saône
country: France
facility: CH de Chalon sur Saône
city: Chambéry
country: France
facility: CH de Chambéry
city: Clamart
country: France
facility: Hôpital Antoine Béclère
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Colmar
country: France
facility: Hôpital Pasteur
city: Corbeil Essonnes
country: France
facility: CH Sud Francilien de Corbeil
city: Créteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon
city: Dunkerque
country: France
facility: CH de Dunkerque
city: Grenoble
country: France
facility: CHU de Grenoble
city: La Roche sur Yon
country: France
facility: CHD La Roche sur Yon
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles - André Mignot
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Kremlin Bicêtre
city: Le Mans
country: France
facility: CH du Mans
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lens
country: France
facility: CH de Lens
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Hurriez
city: Lille
country: France
facility: CH de Saint Quentin
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Mantes-La-Jolie
country: France
facility: CH de Saint Germain
city: Mantes-la-Jolie
country: France
facility: Chi Poissy /Saint- Germain-En-Laye
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: CH de Meaux
city: Metz
country: France
facility: CHR de Metz
city: Montpellier
country: France
facility: Hôpital Saint Eloi
city: Mulhouse
country: France
facility: CHU de Mulhouse
city: Nancy
country: France
facility: CHU Nancy Brabois
city: Nantes
country: France
facility: CHU Hôtel Dieu Nantes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nice
country: France
facility: CHU de Nice
city: Nimes
country: France
facility: CHU de Nîmes - Caremeau
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital de la Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Institut Curie
city: Perpignan
country: France
facility: CH de Perpignan
city: Pessac
country: France
facility: Centre François Magendie
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Reims
country: France
facility: CHU Robert Debré
city: Rennes
country: France
facility: CHU Pontchaillou
city: Roubaix
country: France
facility: CH de Roubaix
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Institut Curie - Centre René Huguenin
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: CHU Bretonneau
city: Valence
country: France
facility: CH Valence
city: Valenciennes
country: France
facility: CH de Valenciennes
city: Vannes
country: France
facility: CH de Bretagne Atlantique
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charité Medical School Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charité Medical School Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: HELIOS Hospital Berlin-Buch
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln
city: Dortmund
country: Germany
facility: St Johannes-Hospital
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus der TU Dresden
city: Düsseldorf
country: Germany
facility: Klinik Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: University of Duisburg-Essen
city: Frankfurt am Main
country: Germany
facility: Krankenhaus Nordwest
city: Freiburg
country: Germany
facility: Universitätklinikum Freiburg Klinik für Innere medizin I
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Göttingen
country: Germany
facility: UniversitätsKrebszentrum Göttingen - G-CCC
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Köln
country: Germany
facility: Uniklinik Köln
city: Leipzig
country: Germany
facility: Klinikum St. Georg gGmbH
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Bologna
country: Italy
facility: Istituto di Ematologia "Saragnoli" Policlinico San'Orsola-Malpighi, Bologna
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Cuneo
country: Italy
facility: Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo
city: Firenze
country: Italy
facility: Azienda Ospedaliera universitaria Careggi
city: Napoli
country: Italy
facility: Ematologia Oncologica Istituto Pascale
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi Melacrino Morelli
city: Roma
country: Italy
facility: Ematologia Università La Sapienza
city: Torino
country: Italy
facility: AOU San Giovanni Battista
city: Udine
country: Italy
facility: Clinica Ematologica di Udine
city: Busan
country: Korea, Republic of
facility: Dong-A Univ. Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asian Medical Center
city: Seoul
country: Korea, Republic of
facility: Korean Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University
city: Lisbon
country: Portugal
facility: Instituto Português Oncologia
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: National University Cancer Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: ICO l'Hospitalet
city: Barcelone
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Girona
country: Spain
facility: ICO - Institut Català d'Oncologia - Hospital Doctor Josep Trueta
city: Jerez de la Frontera
country: Spain
facility: Hospital de Jerez de la Frontera
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Murcia
country: Spain
facility: H. Morales Messeguer
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Sevilla
country: Spain
facility: H. Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset de Valencia
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
Study officials:
affiliation: CH Lyon Sud, Pierre Bénite, France
name: Emmanuel BACHY, Professor
role: STUDY_CHAIR
affiliation: Centre Henri Becquerel, Rouen, France
name: Vincent CAMUS, MD
role: STUDY_CHAIR
References:
citation: 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.