Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
- Conditions
- LymphomaDiffuse Large B-cell Lymphoma
- Interventions
- Drug: Placebo
- Registration Number
- NCT01122472
- Lead Sponsor
- The Lymphoma Academic Research Organisation
- Brief Summary
This study is designed as a phase III, randomized, double-blind, placebo-controlled trial to explore the effect of maintenance therapy with lenalidomide versus placebo on progression-free survival (PFS) in patients treated with R-CHOP responding to induction therapy
For the primary efficacy variable, PFS, an improvement in median PFS from 38.6 months for Treatment Arm B to 54 months for Treatment Arm A (corresponding to a 2-year PFS of 65% vs 73.6%), is considered clinically relevant.
- Detailed Description
Patients should have received at least 6 and up to 8 cycles of the R-CHOP 14 or R-CHOP 21 regimen or 6 R-CHOP-14 or -21 completed by 2 Rituximab alone in accordance to local preferences.
Patients can be registered to participate in the study at two time points:
* At time of initial diagnosis and study enrolment (signature of informed consent) before the first cycle of treatment with R-CHOP.
* At randomization (signature of informed consent) after treatment in first line with R-CHOP and have reached at least PR or CR.
Evaluation of the response to R-CHOP must be in accordance with Revised Response Criteria for Malignant Lymphoma(2007).
Stratification: Before randomization, the patients will be stratified according to the country and the response to R-CHOP (PR vs CR).
Randomization: Patients in CR/PR after R-CHOP will be randomized to maintenance therapy with lenalidomide or placebo.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 650
For patients registered at the time of initial diagnosis
- Patient with histologically proven CD20+ diffuse large B cel LYMPHOMA (DLBCL) 5WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma Or CD20+ Follicular lymphoma grade 3B Or CD20+ Aggressive B-cell lymphoma unclassifiable
- previous untreated with chemo- or radiotherapy
For patients registered after response evaluation to first line treatment with R-CHOP:
- Patient with histologically proven CD20+ diffuse large B cell LYMPHOMA (DLBCL) 5WHO classification 2008) including clinical subtypes (primitive mediastinal, intravascular, etc.). Patients with De Novo Transformed DLBCL from low grade lymphoma (Follicular, other..) may also be included. Patients with DLBCL associated with some small cell infiltration in bone marrow may also be included Or CD20+ B-cell lymphoma with intermediate features between DLBCL and Burkitt or with intermediate features between DLBCL and classical Hodgkin lymphoma Or CD20+ Follicular lymphoma grade 3B Or CD20+ Aggressive B-cell lymphoma unclassifiable
- Have reached a CR or PR after first line treatment with at least 6 cycles of R-CHOP 14 regimens and up to 8 cycles of R-CHOP21
- Previously untreated with Radiotherapy
For all patients:
-
aged from 60 to 80 years at time of registration
-
Ann Arbor stages II-IV at time of initial diagnosis
-
aaIPI> 1 at time of initial diagnosis
-
ECOG performance status 0-2
-
Minimum life expectancy of 3 months
-
Following laboratory values at screening:
- ANC≥ 1000.10^6/L and Platelets≥60000.10^6/L
- AST<5*ULN, ALT<5*ULN, Total Bilirubin<1,5*ULN
- Creatinine clearance>30mL/min
-
Women are are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and after end of study. Men agree not to father a child during participation in the trial and during the 12 months thereafter.
-
Having previously signed a written informed consent form
- Any other histological type of Lymphoma, Burkitt included.
- Any history of treated or non treated small B-cell lymphoma
- Central nervous system or meningeal involvement by lymphoma
- Contraindication to any drug contained in the chemotherapy regimen Myocardial infarction during last 3 months or unstable coronary disease or uncontrolled chronic symptomatic congestive heart insufficiency NYHA III-IV
- Uncontrolled hypertension
- Uncontrolled diabetes mellitus as defined by the investigator
- Active systemic infection requiring treatment
- previously known HIV positive serology
- Active hepatitis B or C
- Prior history of malignancies other than lymphoma within 3 years
- Serious medical or psychiatric illness
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lenalidomide Lenalidomide Lenalidomide daily for 3 weeks every 4 weeks for 24 months Placebo Placebo Placebo daily for 3 weeks every 4 weeks for 24 months
- Primary Outcome Measures
Name Time Method Progression-Free-Survival (PFS) Final PFS analysis will be realized when the number of events (160) has been reached or at the latest when the last patient into the study will finish follow up. The approximate schedule will be 75 months after the first patient randomized. PFS will be measured from the date of randomization to the date of first documented disease progression or death. Progression data will be assigned to the earliest time when any progression is observed without prior missing assessments during the study up to the end of the follow up phase.
- Secondary Outcome Measures
Name Time Method Percentage of patients who convert from PR (partial response) to CR (complete response) 24 months Overall survival (OS) 5 years From the date of randomization to the date of death from any cause Interim analysis of OS will be performed at the time of the PFS final analysis; it is projected to have 97 deaths at this time. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization
Event-Free Survival (EFS) 5 years From the date of randomization to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause Interim analysis of EFS will be performed at the time of the PFS final analysis. Final analysis of OS at the end of the study, defined by the last visit of follow-up for the last patient randomized, 5 years after its randomization
Response rate at the end of maintenance treatment 24 months Safety of lenalidomide in maintenance 5 years Toxicities occured during maintenance phase will be measured and reported from grade 2 for infection and neurological toxicities and from grade 3 for other toxicities according to CTCAE v3
PFS2 5 years From randomization to objective tumor progression on next-line treatment or death from any cause
Trial Locations
- Locations (157)
Oddzial Chorob Rozrostowych Regionalny Osrodek Onkologiczny
🇵🇱Lodz, Poland
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Hopital Saint Joseph
🇧🇪Arlon, Belgium
Medizinische Universität Innsbruck für Innere Medizin
🇦🇹Innsbruck, Austria
AKh Linz - Innere Medizin 3 - Zentrum für Hämatologie un
🇦🇹Linz, Austria
Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Bendigo Hospital
🇦🇺Bendigo, Australia
Frankston Hospital Monash Medical Centre
🇦🇺Frankston, Australia
Austin Hospital
🇦🇺Heidelberg, Australia
Concord Repatriation General Hospital
🇦🇺Concord, Australia
Mater Misericordiae Hospital - Calvary Mater NewCastle
🇦🇺Hunter, Australia
Flinders Medical Centre - Repatriation General Hospital
🇦🇺Daw Park, Australia
LKH Feldkirch
🇦🇹Feldkirch, Austria
Fremantle Hospital
🇦🇺Fremantle, Australia
Canberra Hospital
🇦🇺Garran, Australia
St George Hospital
🇦🇺Kogarah, Australia
Krankenhaus Barmherzigen Schwestern Linz - Abteilung für Inner
🇦🇹Linz, Austria
Sir Charles Gardiner Hospital
🇦🇺Nedlands, Australia
Gold Coast Hospital
🇦🇺Southport, Australia
LKH Leoben-Eisenerz Department für Hämato-Onkologie
🇦🇹Leoben, Austria
Albury Base Hospital/Murray Valley Private Hospital
🇦🇺Wodonga, Australia
Krankenhaus der Elisabethinen Linz GmbH
🇦🇹Linz, Austria
A.Z. Sint Jan AV
🇧🇪Bruges, Belgium
Universitätklinik der PMU Salzburg - Für Innere Medizin III
🇦🇹Salzburg, Austria
Landeskrankenhaus Steyr - Innere Medizin II
🇦🇹Steyr, Austria
Uniersitätsklinik f. Innere Medizin I
🇦🇹Vienna, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Institut Jules BORDET
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
CHR de la Citadelle
🇧🇪Liege, Belgium
Hopital Sainte Elisabeth
🇧🇪Namur, Belgium
Hopital Henri DUFFAUT
🇫🇷Avignon, France
Hopital DUCHENNE
🇫🇷Boulogne sur Mer, France
CH Notre Dame
🇧🇪Charleroi, Belgium
Clinique Notre Dame de Grace
🇧🇪Gosselies, Belgium
AZ VUB
🇧🇪Jette, Belgium
Hopital de BAYONNE
🇫🇷Bayonne, France
CHU Charleroi-Vesale
🇧🇪Charleroi, Belgium
CHU Ambroise Pare
🇧🇪Mons, Belgium
Clinique Saint Joseph
🇧🇪Mons, Belgium
CH de la Tourelle-Peltzer
🇧🇪Verviers, Belgium
Centre de Sante des Fagnes
🇧🇪Chimay, Belgium
Hopital Jolimont
🇧🇪Haine saint paul, Belgium
CH Hutois
🇧🇪HUY, Belgium
A.Z. Sint-Augustinus
🇧🇪Wilrijk, Belgium
Universite Catholique de Louvain Mont Godinne
🇧🇪Yvoir, Belgium
CHR de la Région d'Annecy
🇫🇷Annecy Cedex, France
Heilig Hart Ziekenhuis
🇧🇪Roeselare, Belgium
CH Antibes-Juan les Pins
🇫🇷Antibes, France
CH de Cannes
🇫🇷Cannes, France
CHU Clémenceau- Côte de Nacre
🇫🇷Caen Cedex, France
Centre François Baclesse
🇫🇷CAEN Cedex 05, France
Hôpital de Châlon
🇫🇷Chalon sur Saone, France
Centre Hospitalier
🇫🇷Chambery, France
Institut Daniel Hollard
🇫🇷Grenoble, France
CH de Dunkerque
🇫🇷Dunkerque, France
Hôpital des instructions des Armées PERCY
🇫🇷Clamart, France
Hopital Louis Pasteur
🇫🇷Colmar Cedex, France
CH de Compiègne
🇫🇷Compiegne Cedex, France
CHU le Bocage
🇫🇷Dijon, France
Centre Léon Bérard
🇫🇷LYON Cedex 08, France
CH les CHANAUX
🇫🇷Macon Cedex, France
CHI Fréjus Saint Raphaêl
🇫🇷Frejus, France
CHG La Rochelle
🇫🇷La Rochelle Cedex 01, France
CHU de Lens
🇫🇷Lens, France
Hopital DUPUYTREN
🇫🇷LIMOGES Cedex, France
Clinique de la Sauvegarde
🇫🇷Lyon, France
Institut Paoli Calmettes
🇫🇷Marseille Cedex, France
Centre Azuréen de Cancérologie
🇫🇷Mougins, France
Hôpital Américain de Paris
🇫🇷Neuilly sur seine, France
Centre Henri BECQUEREL
🇫🇷Rouen, France
Hopital Saint Antoine
🇫🇷Paris, France
Hôtel Dieu
🇫🇷Paris Cedex 04, France
Hopital NECKER
🇫🇷Paris, France
Institut Curie
🇫🇷Paris Cedex 05, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite Cedex, France
CH René DUBOS
🇫🇷Pontoise, France
CHI Toulon La Seyne-sur-mer
🇫🇷Toulon, France
Centre René Huguenin
🇫🇷Saint Cloud Cedex, France
CHG Saint Germain
🇫🇷St Germain en Laye, France
Klinika Hematologii Collegium Medicum UJ
🇵🇱Krakow, Poland
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Meir Medical Center
🇮🇱Kfar saba, Israel
Hopital de Troyes
🇫🇷Troyes Cedex, France
CH Valence
🇫🇷Valence Cedex 9, France
Soroka
🇮🇱Beer sheva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Haemek Medical Center
🇮🇱Afula, Israel
Hospitais da Universidade de Coimbra
🇵🇹Coimbra, Portugal
Instituto Português de Oncologia de Lisboa de Francisco Gentil
🇵🇹Lisboa, Portugal
Klinika Nowotworow Ukladu Chlonnego- Centrum Onkologii
🇵🇱Warszawa, Poland
Rabin Medical Center - Beilinson Hospital
🇮🇱Petah Tikwah, Israel
Bnai-Zion medical center
🇮🇱Haifa, Israel
IPO - Francisco Gentil - Porto
🇵🇹Porto, Portugal
Medical University of Warsaw
🇵🇱Warsaw, Poland
Hospital Universitario Fundacion Alcorcon
🇪🇸Alcorcon, Spain
Complejo Hospitalario Universitario de A Coruna
🇪🇸A coruna, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hopital Universitario Virgen de la Arrixaca
🇪🇸El palmar, Spain
Hospital Morales Meseguer
🇪🇸Murcia, Spain
Hospital Central Asturias
🇪🇸Oviedo, Spain
Hopital de Jerez (S.A.S)
🇪🇸Jerez de la frontera, Spain
Hospital de Leon
🇪🇸Leon, Spain
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
CH d'Arras
🇫🇷Arras Cedex, France
CHG Mail Pierre Charlot
🇫🇷Blois, France
Hopital Bicêtre
🇫🇷Le Kremlin-Bicêtre, France
CH de Bourg-en-Bresse
🇫🇷Bourg-en-Bresse, France
Hopital Antoine Béclère
🇫🇷Clamart, France
Hopital André Mignot
🇫🇷Le Chesnay, France
Hôpital Saint Vincent de Paul
🇫🇷Lille, France
CHRU de Lille
🇫🇷Lille Cedex, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hopital St-Louis
🇫🇷Paris, France
Hopital Robert DEBRE
🇫🇷REIMS Cedex, France
Clinique Mathilde
🇫🇷Rouen, France
CHU Purpan Pav. Dieulafoy
🇫🇷Toulouse Cedex 9, France
CH de Valenciennes
🇫🇷Valenciennes, France
Royal Hobart Hospital
🇦🇺Hobart, Australia
Queen Elizabeth Hospital
🇦🇺Woodville, Australia
St Vincent's Hospital, Melbourne
🇦🇺Fitzroy, Australia
Universite Catholique de Louvain Saint Luc
🇧🇪Bruxelles, Belgium
CHU Brugmann
🇧🇪Bruxelles, Belgium
CHU de Liege
🇧🇪Liege, Belgium
AZ Groeninge - Campus Maria s Voorzienigheid
🇧🇪Kortrijk, Belgium
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
Hopital Jean VERDIER
🇫🇷BONDY Cedex, France
Centre Hospitalier de Brive
🇫🇷Brive-La-Gaillarde, France
Centre Hospitalier de Guéret
🇫🇷Gueret, France
Hopital Sud Francilien
🇫🇷Corbeil-Essonnes, France
CHI Evreux
🇫🇷Evreux, France
CH Henri Mondor
🇫🇷Créteil, France
Hopital Nord
🇫🇷Marseille, France
Hopital Notre Dame de Bon Secours
🇫🇷Metz Cedex, France
CH Marc JACQUET
🇫🇷MELUN Cedex, France
CRLC Val d'Aurelle
🇫🇷Montpellier Cedex, France
CHU de Nice
🇫🇷Nice, France
Hopital Emile Muller- CHU Mulhouse
🇫🇷MULHOUSE Cedex, France
Institut Gustave ROUSSY
🇫🇷VILLEJUIF Cedex, France
SPZOZ Zespol Szpitali Miejskich w Chorzowie
🇵🇱Chorzow, Poland
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Hospital Général Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario - La Paz
🇪🇸Madrid, Spain
Hospital Clinico Salamanca
🇪🇸Salamanca, Spain
Hospital Joan XXIII
🇪🇸Tarragona, Spain
Hospital Mutua de Terrassa
🇪🇸Terrassa, Spain
Hôpital d'Avicenne
🇫🇷Bobigny, France
Hopital de la Pitié Salpetrière
🇫🇷Paris Cedex 13, France
Clinique Victor Hugo - Centre Jean Bernard
🇫🇷LE Mans, France
CH Chartres
🇫🇷Chartres Cedex, France
CHG Meaux
🇫🇷Meaux, France
CH de Perpignan
🇫🇷Perpignan, France
Universitario Marques de Valdecilla
🇪🇸Santander, Spain
CHU Nancy Brabois
🇫🇷Vandœuvre-lès-Nancy, France
Clinique Saint Pierre
🇧🇪Ottignies, Belgium
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium