Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP (REMARC)
2021年7月23日 更新者：The Lymphoma Academic Research Organisation
Double Blind Randomized Phase III Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP in First Line
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.
研究概览
详细说明
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.
研究类型
介入性
注册 (实际的)
650
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Afula、以色列、18101
- Haemek Medical Center
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Ashkelon、以色列、78278
- Barzilai Medical Center
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Beer sheva、以色列、84101
- Soroka
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Haifa、以色列、31048
- Bnai-Zion Medical Center
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Kfar saba、以色列、44281
- Meir Medical Center
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Petah Tikwah、以色列、49100
- Rabin Medical Center - Beilinson Hospital
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Rehovot、以色列、76100
- Kaplan Medical Center
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Feldkirch、奥地利、6807
- LKH Feldkirch
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Innsbruck、奥地利、6020
- Medizinische Universität Innsbruck für Innere Medizin
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Leoben、奥地利、8700
- LKH Leoben-Eisenerz Department für Hämato-Onkologie
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Linz、奥地利、4010
- Krankenhaus Der Elisabethinen Linz Gmbh
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Linz、奥地利、4010
- Krankenhaus Barmherzigen Schwestern Linz - Abteilung für Inner
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Linz、奥地利、4021
- AKh Linz - Innere Medizin 3 - Zentrum für Hämatologie un
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Salzburg、奥地利、5020
- Universitätklinik der PMU Salzburg - Für Innere Medizin III
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Steyr、奥地利、4400
- Landeskrankenhaus Steyr - Innere Medizin II
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Vienna、奥地利、A-1090 VIE
- Uniersitätsklinik f. Innere Medizin I
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Wels、奥地利、4600
- Klinikum Wels-Grieskirchen GmbH
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Antwerpen、比利时、2020
- ZNA Middelheim
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Antwerpen、比利时、2060
- ZNA Stuivenberg
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Arlon、比利时、6700
- Hopital Saint Joseph
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Bruges、比利时、8000
- A.Z. Sint Jan AV
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Bruxelles、比利时
- Institut Jules Bordet
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Bruxelles、比利时、1020
- CHU Brugmann
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Bruxelles、比利时
- Université Catholique de Louvain Saint Luc
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Charleroi、比利时、6000
- CH Notre Dame
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Charleroi、比利时、B-6000
- CHU Charleroi-Vesale
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Chimay、比利时、6460
- Centre de Sante des Fagnes
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Gent、比利时、9000
- Universitair Ziekenhuis Gent
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Gosselies、比利时、6041
- Clinique Notre Dame de Grâce
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HUY、比利时、4500
- CH Hutois
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Haine saint paul、比利时、7100
- Hopital Jolimont
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Jette、比利时、1090
- AZ VUB
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Kortrijk、比利时、8500
- AZ Groeninge - Campus Maria s Voorzienigheid
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Liege、比利时、4000
- CHR de la Citadelle
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Liege、比利时、4000
- CHU de Liege
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Mons、比利时、7000
- CHU Ambroise Paré
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Mons、比利时、7000
- Clinique Saint Joseph
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Namur、比利时、5000
- Hopital Sainte Elisabeth
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Ottignies、比利时、1340
- Clinique Saint Pierre
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Roeselare、比利时、8800
- Heilig Hart Ziekenhuis
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Verviers、比利时、4800
- CH de la Tourelle-Peltzer
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Wilrijk、比利时、2610
- A.Z. Sint-Augustinus
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Yvoir、比利时、5530
- Universite Catholique de Louvain Mont Godinne
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Annecy Cedex、法国、74011
- CHR de la Région d'Annecy
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Antibes、法国、06606
- CH Antibes-Juan les Pins
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Arras Cedex、法国、62022
- CH d'Arras
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Avignon、法国、84902
- Hôpital Henri Duffaut
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BONDY Cedex、法国、93143
- Hôpital Jean Verdier
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Bayonne、法国、64100
- Hopital de Bayonne
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Blois、法国、41016
- CHG Mail Pierre Charlot
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Bobigny、法国、93009
- Hôpital d'Avicenne
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Bordeaux、法国、33300
- Polyclinique Bordeaux Nord Aquitaine
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Boulogne sur Mer、法国、62200
- Hopital Duchenne
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Bourg-en-Bresse、法国、01012
- CH de BOURG-EN-BRESSE
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Brive-La-Gaillarde、法国、19100
- Centre Hospitalier de Brive
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CAEN Cedex 05、法国、14026
- Centre François Baclesse
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Caen Cedex、法国、14033
- CHU Clémenceau- Côte de Nacre
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Cannes、法国、06400
- CH de Cannes
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Chalon sur Saone、法国、711100
- Hôpital de Chalon
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Chambery、法国、73011
- Centre Hospitalier
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Chartres Cedex、法国、28018 BP407
- CH Chartres
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Clamart、法国、92140
- Hôpital Antoine Béclère
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Clamart、法国、92140
- Hôpital des instructions des Armées PERCY
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Colmar Cedex、法国、68024
- Hôpital Louis Pasteur
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Compiegne Cedex、法国、60321
- Ch De Compiegne
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Corbeil-Essonnes、法国、91108
- Hopital Sud Francilien
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Créteil、法国、94010
- CH Henri Mondor
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Dijon、法国、21034
- Chu Le Bocage
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Dunkerque、法国、59385
- CH de Dunkerque
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Evreux、法国、27000
- CHI Evreux
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Frejus、法国、83608
- CHI Fréjus Saint Raphaël
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Grenoble、法国、38028
- Institut Daniel Hollard
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Gueret、法国、23000
- Centre Hospitalier de Guéret
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LE Mans、法国、72015
- Clinique Victor Hugo - Centre Jean Bernard
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LIMOGES Cedex、法国、87042
- Hopital Dupuytren
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LYON Cedex 08、法国、69373
- Centre Léon Bérard
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La Rochelle Cedex 01、法国、17019
- CHG La Rochelle
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Le Chesnay、法国、78150
- Hôpital André Mignot
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Le Kremlin-Bicêtre、法国、94275
- Hôpital Bicêtre
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Lens、法国、62307
- CHU de Lens
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Lille、法国、59020
- Hopital Saint Vincent de Paul
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Lille Cedex、法国、59037
- CHRU de Lille
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Lyon、法国、69337
- Clinique de la Sauvegarde
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MELUN Cedex、法国、77011
- CH Marc Jacquet
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MULHOUSE Cedex、法国、68070
- Hopital Emile Muller- CHU Mulhouse
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Macon Cedex、法国、71018
- CH les CHANAUX
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Marseille、法国、13915
- Hôpital Nord
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Marseille Cedex、法国、13273
- Institut Paoli Calmettes
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Meaux、法国、77100
- CHG Meaux
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Metz Cedex、法国、57038
- Hôpital Notre Dame de Bon Secours
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Montpellier Cedex、法国、34298
- CRLC Val d'Aurelle
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Mougins、法国、062250
- Centre Azuréen de Cancérologie
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Neuilly sur seine、法国、92202
- Hopital Americain de Paris
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Nice、法国、06189
- Centre Antoine Lacassagne
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Nice、法国、06202
- Chu De Nice
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Paris、法国、75012
- Hopital Saint Antoine
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Paris、法国、75743
- Hopital Necker
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Paris、法国、75475
- Hopital St-Louis
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Paris Cedex 04、法国、75181
- Hôtel Dieu
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Paris Cedex 05、法国、75248
- Institut Curie
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Paris Cedex 13、法国、75651
- Hôpital de la Pitié Salpêtrière
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Perpignan、法国、66046
- CH de Perpignan
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Pierre Bénite Cedex、法国、64495
- Centre Hospitalier LYON SUD
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Pontoise、法国、95303
- CH René Dubos
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REIMS Cedex、法国、51092
- Hopital Robert Debre
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Rouen、法国、76038
- Centre Henri Becquerel
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Rouen、法国、76175
- Clinique Mathilde
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Saint Cloud Cedex、法国、92211
- Centre René Huguenin
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St Germain en Laye、法国、78105
- CHG Saint Germain
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Toulon、法国、83056
- CHI Toulon La Seyne-sur-mer
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Toulouse Cedex 9、法国、31059
- CHU Purpan Pav. Dieulafoy
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Troyes Cedex、法国、10000
- Hopital de Troyes
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VILLEJUIF Cedex、法国、94805
- Institut Gustave Roussy
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Valence Cedex 9、法国、26953
- CH Valence
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Valenciennes、法国、59322
- CH de Valenciennes
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Vandœuvre-lès-Nancy、法国、54511
- CHU Nancy Brabois
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Chorzow、波兰、41500
- SPZOZ Zespol Szpitali Miejskich w Chorzowie
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Krakow、波兰、31501
- Klinika Hematologii Collegium Medicum UJ
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Lodz、波兰、93509
- Oddzial Chorob Rozrostowych Regionalny Osrodek Onkologiczny
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Warsaw、波兰、02776
- Medical University of Warsaw
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Warszawa、波兰、02781
- Klinika Nowotworow Ukladu Chlonnego- Centrum Onkologii
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Bendigo、澳大利亚、3550
- Bendigo Hospital
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Concord、澳大利亚、2139
- Concord Repatriation General Hospital
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Daw Park、澳大利亚、5000
- Flinders Medical Centre - Repatriation General Hospital
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Fitzroy、澳大利亚、3065
- St Vincent's Hospital, Melbourne
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Frankston、澳大利亚、3199
- Frankston Hospital Monash Medical Centre
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Fremantle、澳大利亚、6160
- Fremantle Hospital
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Garran、澳大利亚、2606
- Canberra Hospital
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Heidelberg、澳大利亚、69126
- Austin Hospital
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Hobart、澳大利亚、7000
- Royal Hobart Hospital
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Hunter、澳大利亚、2310
- Mater Misericordiae Hospital - Calvary Mater NewCastle
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Kogarah、澳大利亚、2217
- St George Hospital
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Nedlands、澳大利亚、6009
- Sir Charles Gardiner Hospital
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Southport、澳大利亚、4215
- Gold Coast Hospital
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Wodonga、澳大利亚、3690
- Albury Base Hospital/Murray Valley Private Hospital
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Woodville、澳大利亚、5011
- Queen Elizabeth Hospital
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Lausanne、瑞士、CH-1011
- Centre Hospitalier Universitaire Vaudois
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Coimbra、葡萄牙、3000 - 075
- Hospitais da Universidade de Coimbra
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Lisboa、葡萄牙、1099 - 023
- Instituto Português de Oncologia de Lisboa de Francisco Gentil
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Lisboa、葡萄牙、1649 - 035
- Hospital de Santa Maria
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Porto、葡萄牙、4200
- IPO - Francisco Gentil - Porto
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A coruna、西班牙、15006
- Complejo Hospitalario Universitario de A Coruña
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Alcorcon、西班牙、28922
- Hospital Universitario Fundacion Alcorcon
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Barcelona、西班牙、08041
- Hospital de La Santa Creu i Sant Pau
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Barcelona、西班牙、08036
- Hospital Clinic Barcelona
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El palmar、西班牙、30120
- Hopital Universitario Virgen de la Arrixaca
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Jerez de la frontera、西班牙、11407
- Hopital de Jerez (S.A.S)
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Leon、西班牙、24080
- Hospital de León
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Madrid、西班牙、28007
- Hospital General Universitario Gregorio Marañón
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Madrid、西班牙、28003
- Hospital 12 de Octubre
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Madrid、西班牙、28046
- Hospital Universitario - La Paz
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Murcia、西班牙、30008
- Hospital Morales Meseguer
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Oviedo、西班牙、33006
- Hospital Central Asturias
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Salamanca、西班牙、37007
- Hospital Clinico Salamanca
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Santander、西班牙、39008
- Universitario Marques de Valdecilla
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Tarragona、西班牙、43007
- Hospital Joan XXIII
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Terrassa、西班牙、08221
- Hospital Mútua de Terrassa
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
60年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Ages Eligible for Study: Between 60 and 80 years old
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Inclusion Criteria:
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
Exclusion Criteria:
- 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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Lenalidomide
Lenalidomide daily for 3 weeks every 4 weeks for 24 months
|
Daily for 3 weeks every 4 weeks for 24 months
其他名称：
|
|
安慰剂比较：Placebo
Placebo daily for 3 weeks every 4 weeks for 24 months
|
Daily for 3 weeks every 4 weeks for 24 months
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Progression-Free-Survival (PFS)
大体时间：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.
|
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.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Overall survival (OS)
大体时间：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
|
5 years
|
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Event-Free Survival (EFS)
大体时间：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
|
5 years
|
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Response rate at the end of maintenance treatment
大体时间：24 months
|
24 months
|
|
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Percentage of patients who convert from PR (partial response) to CR (complete response)
大体时间：24 months
|
24 months
|
|
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Safety of lenalidomide in maintenance
大体时间：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
|
5 years
|
|
PFS2
大体时间：5 years
|
From randomization to objective tumor progression on next-line treatment or death from any cause
|
5 years
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Cottereau AS, Meignan M, Nioche C, Capobianco N, Clerc J, Chartier L, Vercellino L, Casasnovas O, Thieblemont C, Buvat I. Risk stratification in diffuse large B-cell lymphoma using lesion dissemination and metabolic tumor burden calculated from baseline PET/CTdagger. Ann Oncol. 2021 Mar;32(3):404-411. doi: 10.1016/j.annonc.2020.11.019. Epub 2020 Dec 3.
- Vercellino L, Cottereau AS, Casasnovas O, Tilly H, Feugier P, Chartier L, Fruchart C, Roulin L, Oberic L, Pica GM, Ribrag V, Abraham J, Simon M, Gonzalez H, Bouabdallah R, Fitoussi O, Sebban C, Lopez-Guillermo A, Sanhes L, Morschhauser F, Trotman J, Corront B, Choufi B, Snauwaert S, Godmer P, Briere J, Salles G, Gaulard P, Meignan M, Thieblemont C. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020 Apr 16;135(16):1396-1405. doi: 10.1182/blood.2019003526.
有用的网址
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2009年4月1日
初级完成 (实际的)
2016年6月1日
研究完成 (实际的)
2019年9月1日
研究注册日期
首次提交
2010年4月8日
首先提交符合 QC 标准的
2010年5月12日
首次发布 (估计)
2010年5月13日
研究记录更新
最后更新发布 (实际的)
2021年7月26日
上次提交的符合 QC 标准的更新
2021年7月23日
最后验证
2021年7月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.