Studie Mosunetuzumab plus lenalidomid ve srovnání s protilátkou anti-CD20 + chemoterapie u folikulárního lymfomu FLIPI2-5 (MorningLyte)
Randomizovaná, otevřená, mezinárodní, multicentrická studie fáze III hodnotící účinnost a bezpečnost přípravku Mosunetuzumab plus lenalidomid ve srovnání s chemoterapií anti-CD20 monoklonální protilátkou plus u subjektů s dříve neléčeným folikulárním lymfomem FLIPI 2-5
This study is a phase III, randomized, open-label, international, multicenter, interventional trial, designed to compare the efficacy and safety of mosunetuzumab in combination with lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with previously untreated FLIPI 2-5 follicular lymphoma.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
This study is a phase III, randomized, open-label, international, multicenter, interventional trial, designed to compare the efficacy and safety of mosunetuzumab in combination with lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with previously untreated Follicular Lymphoma International Prognostic Index (FLIPI) 2-5 follicular lymphoma This study is composed of a screening period (up to 6 weeks before randomization, i.e., 42 days), a treatment period (30 months i.e., 125w), a safety follow-up period (90 days i.e., 3 months), and a survival follow-up period (up to 7 years after the last randomized patient). The enrollment will last approximately 34 months. The total duration of the study will be therefore approximately 10 years.
Once a patient provides written consent, they may enter the screening phase, with a duration up to 6 weeks prior to randomization and initiation of treatment.
Upon completion of the required assessments in the screening phase, and fulfillment of the eligibility criteria, patients will be randomized. Investigators will be requested to indicate their treatment choice among permitted immuno-chemotherapy regimens just before randomization.
The treatment period for each patient starts with the first intake. The patients will receive protocol-specified treatments until:
- inability to achieve a response at the end of induction phase (at M12 evaluation for experimental arm, and at M6 evaluation for control arms),
- relapse or progression of the disease,
- withdrawal of consent,
- or unacceptable toxicity
In the experimental arm, patients will be treated for 1 cycle of 3 weeks for mosunetuzumab and then 11 cycles of 4 weeks for mosunetuzumab and lenalidomide (47 weeks, around 11 months) during the induction phase, and for a maximum of 9 additional cycles of 8 weeks during the maintenance phase (72 weeks, around 17 months), up to around 125 weeks (30 months). Patients should start the maintenance phase 7 to 8 weeks after the start of last induction cycle (C12).
In the control arm, patients will be treated for 8 or 6 cycles of 3 or 4 weeks for anti-CD20 mAb +cyclophosphamide-doxorubicine-vincristine-prednisone (CHOP) or anti-CD20 mAb + Bendamustine, respectively, depending on the assigned arm (24 weeks, around 5 months) during the induction phase, and for a maximum of 12 additional cycles of 8 weeks during the maintenance phase (96 weeks, around 22 months), up to around 125 weeks (30 months). Patients should start the maintenance phase, 6 to 7 or 7 to 8 weeks after the start of last induction cycle (C8 or C6).
The option to cross-over from the control arm to the experimental arm is not allowed.
All randomized patients will be followed for progression-free survival and overall survival using the same schedule. Patients will be followed up from End of treatment evaluation every 3 months during the first two years, then every 6 months during the next 3 years, then yearly until the end of study.
The end of study will occur when all randomized patients have been followed-up for survival for at least 7 years (or discontinued study early).
Typ studie
Typ studie
Zápis (Odhadovaný)
Zápis
Fáze
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
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Bruges, Belgie, 8000
- AZ SINT-JAN BRUGGE - OOSTENDE AV - Service Hématologie
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Brussels, Belgie, 1070
- INSTITUT JULES BORDET - Service Hématologie
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Brussels, Belgie, 1200
- UNIVERSITE CATHOLIQUE DE LOUVAIN SAINT-LUC - Service Hématologie
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Charleroi, Belgie, 6000
- GRAND HOPITAL DE CHARLEROI - Service Hématologie
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Ghent, Belgie, 9000
- UNIVERSITAIR ZIEKENHUIS GENT - Service Hématologie
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La Louvière, Belgie, 7100
- HELORA - Hôpital de La Louvière - Site Jolimont - Service Hématologie Clinique
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Liège, Belgie, 4000
- CHU DE LIEGE - Service Hématologie
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Yvoir, Belgie, 5530
- CHU UCL NAMUR - SITE GODINNE - Service Hématologie
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Avignon, Francie, 84000
- CH d'AVIGNON - HOPITAL HENRI DUFFAUT - Service d'Onco-Hématologie
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Bayonne, Francie, 64100
- CH DE LA COTE BASQUE - Service Hématologie
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Besançon, Francie, 25030
- CHU JEAN MINJOZ - Service Hématologie
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Bordeaux, Francie, 33076
- INSTITUT BERGONIE - Service d'Oncologie Médicale
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Cahors, Francie, 46005
- CENTRE HOSPITALIER JEAN ROUGIER - Service d'Oncologie - Hématologie
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Chambéry, Francie, 73011
- CH METROPOLE SAVOIE - SITE CHAMBERY - Service Hématologie
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Clermont-Ferrand, Francie, 63003
- CHU ESTAING - Service Thérapie Cellulaire et Hématologie Clinique
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Créteil, Francie, 94010
- HOPITAL HENRI MONDOR - Unité Hémopathies Lymphoïdes
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Dijon, Francie, 21000
- CHU DIJON BOURGOGNE - Service Hématologie Clinique
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La Roche-sur-Yon, Francie, 85925
- CHD DE VENDEE - Service Hématologie
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La Tronche, Francie, 38700
- CHU DE GRENOBLE - Service Hématologie
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Lille, Francie, 59020
- HOPITAL SAINT VINCENT-DE-PAUL - Service Hématologie
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Lille, Francie, 59037
- CHRU DE LILLE - HOPITAL CLAUDE HURIEZ - Service Hématologie
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Limoges, Francie, 87042
- CHU DE LIMOGES - HOPITAL DUPUYTREN - Service Hématologie Clinique et Thérapie Cellulaire
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Marseille, Francie, 13273
- INSTITUT PAOLI CALMETTES - Service Hématologie
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Montpellier, Francie, 34090
- CHU DE MONTPELLIER - Département d'Hématologie Clinique
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Mulhouse, Francie, 68100
- GH REGION MULHOUSE ET SUD ALSACE - HOPITAL EMILE MULLER - Service Hématologie
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Nantes, Francie, 44093
- CHU DE NANTES - Service Hématologie
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Niort, Francie, 79021
- CENTRE HOSPITALIER DE NIORT - Médecine interne
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Paris, Francie, 75475
- HOPITAL SAINT-LOUIS - Service Hématologie
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Pessac, Francie, 33604
- CHU DE BORDEAUX - HOPITAL HAUT-LEVEQUE - CENTRE FRANCOIS MAGENDIE - Service d'Hématologie et Thérapie Cellulaire
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Pierre-Bénite, Francie, 69495
- CHU LYON-SUD - Hématologie
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Poissy, Francie, 78303
- CHI POISSY SAINT-GERMAIN-EN-LAYE - Service Hématologie
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Poitiers, Francie, 86021
- CHU DE POITIERS - HOPITAL DE LA MILETRIE - Service d'Oncologie Hématologique et Thérapie Cellulaire
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Pringy, Francie, 74374
- CH ANNECY GENEVOIS - SITE D'ANNECY - Service Hématologie
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Reims, Francie, 57092
- CHU DE REIMS - HOPITAL ROBERT DEBRE - Service Hématologie
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Rennes, Francie, 35033
- CHU PONTCHAILLOU - Hématologie Clinique
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Rouen, Francie, 76038
- CENTRE HENRI BECQUEREL - Service Hématologie
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Saint-Cloud, Francie, 92210
- INSTITUT CURIE - SITE SAINT-CLOUD - Service Hématologie
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Saint-Priest-en-Jarez, Francie, 42270
- Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne - Service Hématologie
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Strasbourg, Francie, 67033
- INSTITUT DE CANCEROLOGIE STRASBOURG EUROPE - Unité de Recherche Clinique
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Toulouse, Francie, 31059
- IUCT ONCOPOLE - Service Hématologie
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Tours, Francie, 37044
- CHU BRETONNEAU - Service Cancérologie - Hématologie et Thérapie Cellulaire
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Valenciennes, Francie, 59322
- CH DE VALENCIENNES - HOPITAL JEAN BERNARD - Service Hématologie
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Vandœuvre-lès-Nancy, Francie, 54511
- CHU BRABOIS - Service Hématologie
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Vannes, Francie, 56017
- CH DE BRETAGNE ATLANTIQUE - HOPITAL CHUBERT - Service Hématologie
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Villejuif, Francie, 94085
- GUSTAVE ROUSSY CANCER CAMPUS GRAND PARIS - Département Médecine Oncologique
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Amberg, Německo, 92224
- GESUNDHEITSZENTRUM ST. MARIEN GMBH - Hämatologie/Onkologie
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Bamberg, Německo, 96049
- SOZIALSTIFTUNG BAMBERG - KLINIKUM AM BRUDERWALD - Hämatologie und internistische Onkologie
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Berlin, Německo, 10967
- VIVANTES KLINIKUM AM URBAN - Hämatologie und Onkologie
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Berlin, Německo, 13125
- Helios Klinikum Berlin-Buch - Klinik für Hämatologie und Stammzelltransplantation
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Berlin, Německo, 13353
- CHARITE UNIVERSITATSMEDIZIN BERLIN - Med. Klinik m. S. Hämatologie, Onkologie, Tumorimmunologie
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Bremen, Německo, 28205
- KLINIKUM BREMEN-MITTE - Gesundheit Nord gGmbH - Hämatologisch-Onkologische Tagesklinik
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Chemnitz, Německo, 9116
- KLINIKUM CHEMNITZ GGMBH - Klinik f. Innere Medizin III
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Düsseldorf, Německo, 40225
- UNIVERSITÄTSKLINIK DÜSSELDORF-Klinik für Hämatologie, Onkologie und Klinische Immunologie
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Frankfurt, Německo
- GOETHE UNIVERSITÄT FRANKFURT - Medizinische Klinik II Onkologie
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Freiburg im Breisgau, Německo, 79106
- MEDICAL CENTER - UNIVERSITY OF FREIBURG - Klinik für Innere Medizin I Hämatologie, Onkologie und Stammzelltransplantation
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Göttingen, Německo, 37075
- GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizinisched Onkologie
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Halle, Německo, 6097
- UNIVERSITATSKLINIKUM HALLE (SAALE) - Klinik für Innere Medizin IV
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Hanover, Německo, 30459
- KLINIKUM REGION HANNOVER GMBH KLINIK FÜR HÄMATOLOGIE-Onkologie und immunologie
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Heidelberg, Německo, 69120
- UNIVERSITÄTSKLINIKUM HEIDELBERG - Innere Medizin V
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Homburg, Německo, 66421
- Universitätsklinikum des Saarlandes - Klinik für Innere Medizin I - Onkologie, Hämatol. Immun. & Rheumatololgie
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Jena, Německo, 07747
- UNIVERSITÄTSKLINIKUM JENA-Klinik für Innere Medizin II
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Kaiserslautern, Německo, 67655
- WESTPFALZ KLINIKUM - Klinik für Innere Medizin I
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Kiel, Německo, 24105
- UKSH UNIVERSITAETSKLINIKUM SCHLESWIG-HOLSTEIN - Med. Klinik II - Hämatologie und Onkologie
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Koblenz, Německo, 56073
- GEMEINSCHAFTSKLINIKUM MITTELRHEIN GGMBH - Innere Medizin - Hämatologie/Onkologie
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Landshut, Německo, 84036
- LAKUMED KLINIKUM - Onkologisches und palliativmedizinisches Netzwerk Landshut
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Lübeck, Německo, 23538
- UNIVERSITATSKLINIKUM LUBECK - Klinik für Hämatologie und Onkologie
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Mönchengladbach, Německo, 41063
- KLINIKEN MARIA HILF GMBH KRANKENHAUS ST. FRANZISK - Hämatologie, Onkologie & Gastroenterologie
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München, Německo, 81377
- KLINIKUM GROSSHADERN DER LMU MUNCHEN - Hämatologie und Onkologie allgemein
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München, Německo, 81675
- KLINIKUM RECHTS DER ISAR, III MED KLINIK DER TU - Hämatologie und Onkologie
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Münster, Německo, 48149
- Gemeinschaftspraxis Fur Hamatologie Und Onkologie
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Münster, Německo, 48149
- Universtatsklinikum Munster
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Paderborn, Německo, 33098
- BRUEDERKRANKENHAUS ST. JOSEF PADERBORN - Klinik für Hämatologie und Onkologie
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Ravensburg, Německo, 86212
- MVZ FÜR HÄMATOLOGIE UND ONKOLOGIE RAVENSBURG GMBH - Hematology
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Regensburg, Německo, 93053
- UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III
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Reutlingen, Německo, 72764
- KLINIKUM AM STEINENBERG REUTLINGEN GMBH - Medizinische Klinik I
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Rostock, Německo, 18057
- UNIVERSITÄT ROSTOCK - Hämatologie/Onkologie
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Rotenburg (Wümme), Německo, 27356
- AGAPLESION DIAKONIEKLINIKUM ROTENBURG - Klinik für Hämatologie, Onkologie und Nephrologie
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Ulm, Německo, 89081
- UNIV KLINIKUM ULM - INNERE MEDIZIN III - Service Hématologie
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Wuppertal, Německo, 42283
- HELIOS UNIVERSITÄTSKLINIKUM WUPPERTAL - Hämatologie und Onkologie
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Würzburg, Německo, 97080
- UNIVERSITY WURZBURG - Hämatologie
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Lisbon, Portugalsko, 1099
- INSTITUTO PORTUGUES DE ONCOLOGIA DE LISBOA FRANCISCO GENTIL - Departamento Hematologia
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Graz, Rakousko, 8020
- Krankenhaus der Barmherzigen Brüder Graz - Abteilung Für Innere Medizin I
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Krems, Rakousko, 3500
- Krems University Hospital - Abteilung Für Innere Medizin 2
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Leoben, Rakousko, 8700
- LKH HOCHSTEIERMARK - Department für Hämato-Onkologie
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Linz, Rakousko, 4021
- Kepler Universitaetsklinikum - Univ.-Klinik für Hämatologie und Internistische Onkologie
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Salzburg, Rakousko, 5020
- Paracelsus Medical University - 3rd Medical Department
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Sankt Pölten, Rakousko, 3100
- Univ. Klinikum ST.PÖLTEN - Klinische Abteilung Für Innere Medizin 1
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Vienna, Rakousko, 1090
- Medical University of Vienna - Department of Hematology and Hemostaseology
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Wels, Rakousko, 4600
- Klinikum Wels-Grieskirchen GMBH - IVth Internal Department
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Albacete, Španělsko, 02006
- HOSPITAL UNIVERSITARIO DE ALBACETE-Servicio de Hematologia
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Barcelona, Španělsko, 08908
- HOSPITAL DURAN I REYNALS - ICO Oncologia
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Barcelona, Španělsko, 8025
- HOSPITAL DE LA SANTA CREU I SANT PAU - Servicio de Hematología
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Barcelona, Španělsko, 8035
- HOSPITAL VALL D'HEBRON - Hematology Service
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Barcelona, Španělsko, 8036
- HOSPITAL CLINIC BARCELONA - Hematology department
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Las Palmas de Gran Canaria, Španělsko, 35010
- HOSPITAL UNIVERSITARIO DR. NEGRIN-Servicio de Hematologia
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Lleida, Španělsko, 25198
- HOSPITAL UNIVERSITARIO ARNAU DE VILANOVA - Servicio Hematologia
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Madrid, Španělsko, 28006
- HOSPITAL UNIVERSITARIO DE LA PRINCESA - Hematología
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Madrid, Španělsko, 28007
- HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARANON - Servicio de Hematología-UTMO
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Madrid, Španělsko, 28041
- HOSPITAL 12 DE OCTUBRE - Servicio de Hematología y Hemoterapia
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Madrid, Španělsko, 28222
- HOSPITAL PUERTA DEL HIERRO - Servicio Hematologia
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Madrid, Španělsko, 28922
- HOSPITAL UNIVERSITARIO FUNDACION ALCORCON - Consulta de Hematología Hospital de Día Médico
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Marbella, Španělsko, 29603
- HOSPITAL COSTA DEL SOL MARBELLA - Servicio de hematologia
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Oviedo, Španělsko, 33011
- HOSPITAL CENTRAL ASTURIAS - Servicio de Hematología
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Salamanca, Španělsko, 37007
- HOSPITAL CLINICO SALAMANCA - Servicio de Hematologia
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Valencia, Španělsko, 46010
- HOSPITAL CLINICO DE VALENCIA - Servicio de Hematologia
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Bellinzona, Švýcarsko, 6500
- Oncology Institute of Southern Switzerland (IOSI) - Department of Oncology
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Chur, Švýcarsko, 7000
- Kantonsspital Graubunden - Departement Innere Medizin Medizinische Onkologie und Hämatologie
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Geneva, Švýcarsko, 1205
- Hôpitaux Universitaires de Genève (HUG) - Hématologie
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Olten, Švýcarsko, 4600
- Kantonsspital Olten - Hämatologie
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Thun, Švýcarsko, 3600
- Spital STS AG - Onkologie und Hämatologiezentrum
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Villars-sur-Glâne, Švýcarsko, 1752
- HFR Fribourg - Hématologie
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
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1. Patient with histologically proven previously untreated CD20+ follicular lymphoma grade 1, 2, or 3a (including patient watched during up to 10 years after initial diagnosis) as assessed by the investigators according to the WHO 2016 classification12, or classical follicular lymphoma according to the WHO 2022 classification13. Diagnostic tissue must be available for central pathology review, exploratory endpoints and secondary data use.
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FLIPI 2-5.
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All Ann Arbor stages (including stage I if FLIPI ≥ 2).
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Must need treatment as evidenced by at least one of the following criteria:
4.1. Bulky disease defined as one of the following: 4.1.1. a nodal or extranodal mass/lesion > 70 mm in its largest diameter or, 4.1.2. involvement of at least 3 different nodal or extranodal sites (each with a diameter greater than > 30 mm) 4.2. Presence of at least one of the following B symptoms within the prior 6 months: 4.2.1. fever (> 38°C) of unclear etiology 4.2.2. night sweats 4.2.3. weight loss greater than 10% 4.3. Symptomatic splenomegaly 4.4. Symptomatic lesion: 4.4.1. painful lesion and/or 4.4.2. any compressive syndrome (for example, but not restricted to- ureteral, orbital, gastrointestinal) 4.5. Any one of the following cytopenias due to lymphoma: 4.5.1. hemoglobin < 10g/dL (6.25 mmol/L) 4.5.2. platelets <100 x 109/L, or 4.5.3. absolute neutrophil count (ANC) < 1.5 x 109/L 4.6. Pleural or peritoneal serous effusion (irrespective of cell content) 4.7. Abnormal biological prognostic parameters: (item not applicable for Germany) 4.7.1. β2microglobulin > ULN or 4.7.2. LDH > ULN
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At least one bi-dimensionally measurable nodal lesion, defined as > 15 mm in its longest dimension, or at least one bi-dimensionally measurable extra nodal lesion, defined as > 10 mm in its longest dimension (and FDG-avid lesion).
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Participant who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures.
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Must be ≥ 18 years old at the time of signing the informed consent form (ICF).
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ECOG performance status 0 to 2.
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Estimated minimum life expectancy of 3 months.
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Adequate hematological function within 28 days prior to randomization, including:
10.1. Absolute neutrophil count (ANC) ≥ 1 x 109/L 10.2. Platelet count ≥ 75 x 109/L, or ≥ 30 x 109/L if bone marrow infiltration or splenomegaly 10.3. Hemoglobin ≥ 8.0 g/dL (5 mmol/L) unless related to bone marrow infiltration or splenomegaly. Transfusion is allowed before starting treatment (no required window)
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Normal laboratory values:
11.1. Measured or estimated creatinine clearance ≥ 40mL/min calculated by institutional standard method (MDRD or Cockcroft-Gault 11.2. AST or ALT ≤ 2.5 x the upper limit of normal (ULN), except in patients with documented liver or pancreatic involvement by lymphoma ≤ 5 x ULN 11.3. Serum total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for patients with Gilbert syndrome), except in patients with documented liver or pancreatic involvement by lymphoma ≤ 3 x ULN
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LVEF within normal range (i.e. > 50% as evaluated by Transthoracic Echocardiography or > 45% as evaluated by isotopic method (MUGA scan).
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Participants should be able to receive adequate prophylaxis and/or therapy for thromboembolic events (aspirin, low molecular weight heparin or direct oral anticoagulants).
Patients with a curative anticoagulation therapy can be enrolled. A patient with deep vein thrombosis due to compressive syndrome is eligible if a curative anticoagulation therapy has been started at least 1 week before initiating study treatment: low molecular weight heparin possible at treatment onset, then direct oral anticoagulants according to local practices.
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Must be able to adhere to the study visit schedule and other protocol requirements.
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No more applicable following SM#14
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Negative HIV test before randomization, with the following exception:
Patients with a positive HIV test before randomization are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.
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For women of childbearing potential (WOCBP) :
- must have a negative result for pregnancy test (highly sensitive serum) within 7 days before randomization and within 7 days before initiation of study treatment.
- must agree to abstain from becoming pregnant or breastfeeding, and agree to use highly effective contraceptive methods during study participation, and for at least 28 days after the final dose of lenalidomide (if applicable), 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable), 12 months after the final dose of CHOP (if applicable), 6 months after the final dose of bendamustine (if applicable), 12 months after the final dose of rituximab (if applicable), and 18 months after the final dose of obinutuzumab (if applicable).
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For men with a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period (including periods of treatment interruption), and for at least 07 days after the final dose of lenalidomide (if applicable), 2 months after the final dose of tocilizumab (if applicable), 6 months after the final dose of CHOP (if applicable), 3 months after the final dose of bendamustine (if applicable), 12 months after the final dose of rituximab (if applicable), and 3 months after the final dose of obinutuzumab (if applicable). Men must also agree to refrain from donating sperm from the first day of treatment until at least 7 days after the final dose of lenalidomide (if applicable), 2 months after the final dose of tocilizumab (if applicable), 6 months after the final dose of CHOP (if applicable), 3 months after the final dose of bendamustine (if applicable), 12 months after the final dose of rituximab (if applicable), and 3 months after the last dose of obinutuzumab (if applicable).
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Participant covered by any social security system (France).
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Participant who understands and speaks one of the country official languages, unless local regulation authorizes independent translators.
Exclusion criteria:
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Grade 3b follicular lymphoma according to the WHO 2016 classification12, or follicular large B-cell lymphoma according to the WHO 2022 classification13
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Suspicion or clinical evidence of transformed lymphoma at enrollment by investigator assessment.
Examples: patients with high or intermediate high SUV (>20) in any nodal or extranodal site particularly in the bones (vertebrae etc) unless biopsy proven to be genuine FL grade 1,2, 3A ; and/or discordant (e.g. SUV doubled) with SUV of other sites including the biopsy site.; and/or LDH > 2.5 x ULN in a context of rapidly progressive disease, etc. Please contact the Coordinating Investigator / Sponsor to discuss such cases or if there is any doubt before considering enrolment.
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Prior localized radiotherapy for the FL.
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Prior history of another lymphoma.
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Uncontrolled symptomatic pleural or serous effusion requiring urgent treatment (within one week of finding). Participants may only be enrolled after Coordinating investigator / sponsor approval once confirmed participant is durably asymptomatic after adequate pleural/serous drainage or only if an efficient drainage device (e.g.pleurX™) is in place before randomization.
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Uncontrolled symptomatic ureterohydronephrosis resulting in renal failure. Participants with adequate management i.e. ureteral catheter or double J stent allowing renal failure control are eligible only if urinary catheter is in place before randomization.
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Presence or history of symptomatic or threatening lymphomatous epidural/nerve root lesion, even such participants whose disease is controlled by short course of steroids are NOT eligible.
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Use of any standard or experimental anti-cancer drug therapy within 45 days of the start (Day 1) of study treatment.
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Any contraindication to any drug contained in the study treatment control arms or in the Auxiliary Medicinal Products (AxMPs)
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Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) and corticosteroids on the long run with the following exceptions: inhaled steroids for asthma, topical steroids, or replacement or stress corticosteroids during the study at any time. Participants who require lymphoma symptom control during screening may receive corticosteroid < or = 1mg/kg/day prednisone or equivalent for a maximum of 10 days prior to first dose of study treatment
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Received a live, attenuated vaccine within 4 weeks before the first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 6 months after the final dose of study treatment.
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Major surgery (excluding surgical documentation of FL) within 28 days prior to signing informed consent.
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Seropositive for or active viral infection with hepatitis B virus (HBV):
- HBsAg positive
- HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA (Patients who are HBsAg negative, anti-HBs positive and/or anti-HBc positive but viral DNA negative are eligible. They should be treated and perform testing at regular interval described in section Anti infectious prophylaxis; Patients who are seropositive due to a history of hepatitis B vaccine (anti-HBs positive) are eligible).
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Known seropositive for, or active infection hepatitis C virus (HCV) (Patients who are positive for HCV antibody with a negative viral RNA are eligible).
-
Known or suspected hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab, anti-CD20 mAb, tocilizumab, lenalidomide formulation, including mannitol; or to any of the excipients.
-
History of solid organ transplantation or allogeneic stem cell transplant (SCT).
-
Active autoimmune disease requiring treatment.
-
History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, uveitis, or glomerulonephritis.
- Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
- Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
- Participants with a remote history of, or well-controlled autoimmune disease, with a treatment-free interval from immunosuppressive therapy for 12 months may be eligible after review and discussion with the Coordinating investigator.
-
Participants with any active infection such as known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds), known or suspected chronic active Epstein-Barr virus (EBV) infection are excluded.
-
Evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to:
- significant cardiovascular disease [e.g., Objective Class C or D heart diseases (cf. Classes of Heart Failure | American Heart Association), myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina)
- significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
- clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
- current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 1 year and have no residual neurologic deficits as judged by the investigator are allowed. Participants with a history of epilepsy who have had no seizures in the past 2 years with or without anti-epileptic medications can be eligible.
-
History of confirmed progressive multifocal leukoencephalopathy (PML).
-
Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
-
History of erythema multiforme, Grade ≥3 rash, or blistering rash following prior treatment with immunomodulatory derivatives.
-
History of interstitial lung disease (ILD), drug-induced pneumonitis, and autoimmune pneumonitis.
-
Active malignancy other than the one treated in this research. Prior history of malignancies unless the patient has been free of the disease and therapy for ≥ 3 years. However, patients with a single occurrence of the following conditions that have been treated with curative intent are eligible:
- Localized non-melanoma skin cancer.
- Carcinoma in situ of the cervix.
- Carcinoma in situ of the breast.
- Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node Metastasis [TNM] staging system) or prostate cancer.
-
Presence or history of CNS or meningeal involvement by lymphoma.
-
Pregnant, planning to become pregnant or lactating WOCBP.
-
Any significant medical conditions, including the presence of laboratory abnormality or psychiatric illness which places the patient at unacceptable risk if he/she were to participate in the study, and likely to interfere with participation in this clinical study (according to the investigator's decision) or which confounds the ability to interpret data from the study.
-
Person deprived of his/her liberty by a judicial or administrative decision.
-
Person hospitalized without consent.
-
Adult person under legal protection.
-
Patients with absolute lymphocyte count > 20 G/L before randomization. Participants circulating lymphoma cell≥ 5 G/L must be discussed with the Sponsor before randomization.
NB: for 29-31., if there is an individual benefit for such patients, an Ethics Committee will have to be informed case by case.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Experimentální: Mosun-Len
Mosunetuzumab + lenalidomide |
5 mg (step-up dosing) Day 1 of C1 45 mg Day 8 and Day 15 of C1, 45 mg Day 1 from C2 to C12, 45 mg Day 1 from C13 to C21 Lenalidomide starting dose is based on patient's creatinine clearance. Day 1 to Day 21 from C2 to C12 |
|
Aktivní komparátor: R-CHOP
Rituximab-CHOP |
when associated to CHOP IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C20 750 mg/m2 Day 1 from C1 to C6 50 mg/m2 Day 1 from C1 to C6 1.4 mg/m2 (cap cf. below)$ Day 1 from C1 to C6 100 mg/day Day 1 to Day 5 from C1 to C6 when associated to bendamustin IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C18 |
|
Aktivní komparátor: G-CHOP
Obinutuzumab-CHOP |
750 mg/m2 Day 1 from C1 to C6 50 mg/m2 Day 1 from C1 to C6 1.4 mg/m2 (cap cf. below)$ Day 1 from C1 to C6 100 mg/day Day 1 to Day 5 from C1 to C6 when associated to CHOP 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C18 when associated to bendamustin 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C20 |
|
Aktivní komparátor: R-Benda
Rituximab-Bendamustin |
when associated to CHOP IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C20 when associated to bendamustin IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C18 90 mg/m2 Day 1 and Day 2 from C1 to C6 |
|
Aktivní komparátor: G-Benda
Obinutuzumab-Bendamustin |
when associated to CHOP 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C18 when associated to bendamustin 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C20 90 mg/m2 Day 1 and Day 2 from C1 to C6 |
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Progression Free Survival (PFS)
Časové okno: 130 PFS events assessed by an Independent Review Committee (IRC) (4.6 years)
|
time from randomization to the date of first documented disease progression/relapse or death from any cause, by Lugano 2014 |
130 PFS events assessed by an Independent Review Committee (IRC) (4.6 years)
|
|
Progression Free Survival (PFS)
Časové okno: 173 PFS events assessed by IRC (5.8 y)
|
time from randomization to the date of first documented disease progression/relapse or death from any cause, by Lugano 2014 |
173 PFS events assessed by IRC (5.8 y)
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Výskyt a závažnost nežádoucích účinků (AE) včetně závažných nežádoucích účinků a nežádoucích účinků se zvláštním zájmem (SAE a AESI)
Časové okno: 4,6 roku
|
4,6 roku
|
|
|
Výskyt a závažnost AE včetně SAE a AESI
Časové okno: 5,8 roku
|
5,8 roku
|
|
|
Snášenlivost, jak byla hodnocena výskytem přerušení dávkování, zpoždění, snížení dávky a přerušení léčby ve studii
Časové okno: 4,6 roku
|
4,6 roku
|
|
|
Snášenlivost, jak byla hodnocena výskytem přerušení dávkování, zpoždění, snížení dávky a přerušení léčby ve studii
Časové okno: 5,8 roku
|
5,8 roku
|
|
|
Výskyt druhých primárních malignit (SPM)
Časové okno: 4,6 roku
|
4,6 roku
|
|
|
Výskyt druhých primárních malignit (SPM)
Časové okno: 5,8 roku
|
5,8 roku
|
|
|
protilékové protilátky (ADA) k mosunetuzumab
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Maximální sérová koncentrace mosunetuzumabu - Cmax
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Minimální sérová koncentrace mosunetuzumabu - Cmin
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Plocha pod křivkou sérové koncentrace mosunetumabu - AUC
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Maximální sérová koncentrace lenalidomidu - Cmax
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Minimální sérová koncentrace lenalidomidu - Cmin
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Plocha pod křivkou sérové koncentrace lenalidomidu - AUC
Časové okno: každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
každý cyklus, 18 měsíců, 24 měsíců, 30 měsíců
|
|
|
Overall Response (OR)
Časové okno: 6 months
|
by Lugano 2014 (PET-CT based response), assessed by investigator and IRC |
6 months
|
|
Complete Metabolic Rate (CMR)
Časové okno: 6 months
|
by Lugano 2014 (PET-CT based response), assessed by investigator and IRC |
6 months
|
|
Overall Response (OR)
Časové okno: 12 months
|
by Lugano 2014 (PET-CT based response), assessed by investigator and IRC |
12 months
|
|
Complete Metabolic Rate (CMR)
Časové okno: 12 months
|
by Lugano 2014 (PET-CT based response), assessed by investigator and IRC |
12 months
|
|
Overall Response (OR) and Complete Response (CR) rate at EOT
Časové okno: 4.6 years
|
by Lugano 2014 (PET-CT based response), assessed by investigator and IRC |
4.6 years
|
|
Best Overall Response (CR or PR) rate
Časové okno: 5.8 years
|
by Lugano 2014 (PET-CT based response), assessed by investigator and IRC |
5.8 years
|
|
Progression of disease within 2 years (POD24)
Časové okno: 2 years
|
rate of progression of disease (POD) within 2 years of first line therapy |
2 years
|
|
PFS
Časové okno: 4.6 years
|
by Lugano 2014, assessed by investigator |
4.6 years
|
|
PFS
Časové okno: 5.8 years
|
by Lugano 2014, assessed by investigator |
5.8 years
|
|
Event Free Survival (EFS) by Lugano 2014
Časové okno: 4.6 years
|
time between randomization and date of first documented disease progression/relapse, initiation of a new anti-lymphoma treatment or death from any cause |
4.6 years
|
|
Event Free Survival (EFS) by Lugano 2014
Časové okno: 5.8 years
|
time between randomization and date of first documented disease progression/relapse, initiation of a new anti-lymphoma treatment or death from any cause |
5.8 years
|
|
Time to Next Anti-Lymphoma Treatment (TTNLT)
Časové okno: 4.6 years
|
time between randomization and date of first documented administration of any new anti-lymphoma treatment |
4.6 years
|
|
Time to Next Anti-Lymphoma Treatment (TTNLT)
Časové okno: 5.8 years
|
time between randomization and date of first documented administration of any new anti-lymphoma treatment |
5.8 years
|
|
Duration of response
Časové okno: 4.6 years
|
defined for patients with a best overall response of CR or PR determined by Lugano 2014 (PET-CT based response), defined as the time of 1st occurrence of CR or PR to disease progression/relapse or death from any cause |
4.6 years
|
|
Duration of response
Časové okno: 5.8 years
|
defined for patients with a best overall response of CR or PR determined by Lugano 2014 (PET-CT based response), defined as the time of 1st occurrence of CR or PR to disease progression/relapse or death from any cause |
5.8 years
|
|
Overall Response (OR)
Časové okno: End of treatment (12 months for experimental arm, 6 months for comparative arms)
|
assessed by investigator and IRC |
End of treatment (12 months for experimental arm, 6 months for comparative arms)
|
|
Duration of complete response
Časové okno: 4.6 years
|
for patients with a best overall response of CR determined by Lugano 2014 (PET-CT based response), define as the time of first occurrence of CR to disease progression/relapse or death from any cause |
4.6 years
|
|
Duration of complete response
Časové okno: 5.8 years
|
for patients with a best overall response of CR determined by Lugano 2014 (PET-CT based response), define as the time of first occurrence of CR to disease progression/relapse or death from any cause |
5.8 years
|
|
Overall Survival (OS)
Časové okno: 4.6 years
|
time from randomization to death from any cause |
4.6 years
|
|
Overall Survival (OS)
Časové okno: 5.8 years
|
time from randomization to death from any cause |
5.8 years
|
|
Time to deterioration in physical functioning
Časové okno: baseline, 6 months, 12 months, 18 months, 24 months, 30 months or end of treatment
|
EORTC QLQ-C30 quality of life questionnaire |
baseline, 6 months, 12 months, 18 months, 24 months, 30 months or end of treatment
|
|
Time to deterioration in lymphoma symptoms
Časové okno: baseline, 6 months, 12 months, 18 months, 24 months, 30 months or end of treatment
|
FACTLym LYMS quality of life questionnaire |
baseline, 6 months, 12 months, 18 months, 24 months, 30 months or end of treatment
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Spolupracovníci
Spolupracovníci
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Franck MORSCHHAUSER, Lymphoma Study Association
- Vrchní vyšetřovatel: Christian BUSKE, GLA
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Novotvary
- Onemocnění imunitního systému
- Novotvary podle histologického typu
- Lymfatická onemocnění
- Lymfoproliferativní poruchy
- Imunoproliferativní poruchy
- Lymfom, Non-Hodgkin
- Lymfom
- Hemická a lymfatická onemocnění
- Lymfom, folikulární
- Aminokyseliny, peptidy a proteiny
- Proteiny
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Benzimidazoly
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Uhlovodíky
- Uhlovodíky, cyklické
- Uhlohydráty
- Kyseliny, acyklické
- Karboxylové kyseliny
- Alkaloidy
- Polycyklické aromatické uhlovodíky
- Uhlovodíky, aromatické
- Polycyklické sloučeniny
- Glykosidy
- Piperidiny
- Indoly
- Protilátky, monoklonální
- Protilátky
- Imunoglobuliny
- Imunoproteiny
- Krevní proteiny
- Sérové globuliny
- Globuliny
- Těhotenství
- Těhotenství
- Steroidy
- Sloučeniny roztaveného kruhu
- Fosforamidové hořčice
- Sloučeniny hořčice dusíku
- Hořčičné sloučeniny
- Uhlovodíky, halogenované
- Fosforamidy
- Organofosforové sloučeniny
- Těhotenství
- Vinca alkaloidy
- Alkaloidy tryptaminu sezologaninu
- Indolské alkaloidy
- Indolizidiny
- Indoliziny
- Antracykliny
- Nafthacenes
- Aminoglykosidy
- Butyráty
- Protilátky, monoklonální, omyl odvozený
- Daunorubicin
- Fthalimidy
- Kyseliny ftalové
- Kyseliny, karbocyklické
- Piperidony
- Isoindoly
- Lenalidomid
- Bendamustin hydrochlorid
- Rituximab
- Prednison
- Cyklofosfamid
- Doxorubicin
- Vinkristine
- Obinutuzumab
Další identifikační čísla studie
Další identifikační čísla studie
- MorningLyte
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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