Selinexor (KPT-330) in pazienti con linfoma diffuso a grandi cellule B recidivato/refrattario (DLBCL)
Uno studio di fase 2b in aperto su Selinexor (KPT-330) in pazienti con linfoma diffuso a grandi cellule B recidivato/refrattario (DLBCL)
A multicenter, open-label Phase 2b study of selinexor (KPT-330) in participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have no therapeutic options of demonstrated clinical benefit.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
This is a multicenter, open label, Phase 2b study of the selective inhibitor of nuclear export (SINE) selinexor (40 or 60 milligrams [mg]) given orally (PO) to participants with R/R DLBCL). The study is being conducted in 2 parts (Part 1 and Part 2). For Part 1, a fixed 60 mg dose of selinexor is given orally to 130 participants with R/R DLBCL who have no therapeutic options of demonstrated clinical benefit and who meet eligibility criteria and have none of the exclusion criteria will be enrolled to receive selinexor until either disease progression or intolerance has occurred. For Part 2, approximately 110 participants (55 in each arm) are planned to be enrolled. Participants will be randomized (open label) in a 1:1 ratio to either Arm A (40 mg) or Arm B (60 mg) and will be stratified based on history of prior autologous stem cell transplantation (ASCT) versus no prior ASCT. All the participants will be followed until disease progression and/or death.
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- St. Vincent's Hospital Sydney
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Liverpool, New South Wales, Australia, 2170
- Liverpool Hospital, Ingham Institute of Medical Research
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Waratah, New South Wales, Australia, 2298
- Calvary Mater Newcastle Hospital
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Queensland
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South Brisbane, Queensland, Australia, 4101
- Icon Cancer Care
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South Australia
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Adelaide, South Australia, Australia, 5000
- Royal Adelaide Hospital
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Kurralta Park, South Australia, Australia, 5037
- Ashford Cancer Centre
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash Medical Centre
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East Melbourne, Victoria, Australia, 3001
- Epworth Hospital
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Fitzroy, Victoria, Australia, 3065
- St. Vincent's Melbourne
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Melbourne, Victoria, Australia, 3004
- The Alfred Hospital
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Western Australia
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Murdoch, Western Australia, Australia, 6150
- Fiona Stanley Hospital
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Graz, Austria, 8036
- Medical University of Graz
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Innsbruck, Austria
- Medizinische Universität Innsbruck für Innere Medizin
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Leoben, Austria, 8700
- LKH Leoben Department for Haemato-Oncology
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Linz, Austria
- Akh Linz Innere Med III - Zentrum für Hämatologie und med. Onkologie
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Linz, Austria
- Krankenhaus Barmherzigen Schwestern Linz
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Linz, Austria
- Krankenhaus der Elisabethinen Linz GmbH
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Salzburg, Austria, A-5020
- Uni. Klinik für Innere Medizin III Universitätsklinikum der PMU LKH Salzburg
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Vienna, Austria
- Medical University of Vienna (MUW) Department of Medicine I
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Vienna, Austria
- Univ. General Hospital Hietzing
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Antwerp, Belgio
- Ziekenhuis Netwerk Antwerpen
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Bruges, Belgio, 8000
- AZ Sint-Jan
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Brussels, Belgio, 1000
- Institut Jules Bordet
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Brussels, Belgio
- Cliniques Universitaires Saint-Luc
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Ghent, Belgio, 9000
- UZ Gent
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La Louvière, Belgio, 7100
- CH Jolimont
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Roeselare, Belgio
- AZ Delta
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Roeselare, Belgio
- H-Hartziekenhuis Roeselare-Menen
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Pleven, Bulgaria, 5800
- University Hospital for Active Treatment Dr. Georgi Stranski
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Sofia, Bulgaria, 1431
- University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD
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Sofia, Bulgaria, 1756
- Specialized Hospital for Active Treatment of Haematological Diseases EAD
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Ontario
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Toronto, Ontario, Canada
- Princess Margaret Cancer Centre
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Quebec
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Montreal, Quebec, Canada
- Sir Mortimer B Davis Jewish General Hospital/McGill University
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Créteil, Francia
- Centre Hospitalier Universitaire Henri Mondor
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Créteil, Francia
- Unite Hemopathies Lymphoides Chu Henri Mondor
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Dijon, Francia
- Chu Dijon-Bourgogne - Hematologie Clinique
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La Rochelle, Francia
- Hospitalier de la Rochelle-Ré-Aunis
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Lille, Francia
- CHRU de Lille - Hopital Claude-Huriez
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Marseille, Francia
- Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
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Montpellier, Francia
- CHU Montpellier
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Paris, Francia
- Pitié-Salpêtrière Hospital
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Paris, Francia, 75010
- Hostpial Saint Louis - CIRCO (Centre d'Investigations et de Recherche Clinique en Oncologie)
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Paris, Francia
- Hôpital Necker Service d'Hématologie Adult
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Rouen, Francia
- Centre Henri Becquerel
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Lyon
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Pierre-Bénite, Lyon, Francia
- CHU Lyon Sud
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Aachen, Germania
- Uniklinik Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
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Bad Saarow, Germania
- HELIOS Klinikum Bad Saarow
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Berlin, Germania
- Charite Universitatsmedizin Berlin (Benjamin Franklin Campus)
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Berlin, Germania
- Charite Universitatsmedizin Berlin (Virchow Campus)
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Bremen, Germania, 28239
- Ev. Diakonie-Krankenhaus gGmbH
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Cologne, Germania
- Klinikum Kempten Klinik für Innere Medizin III - Hämatologie, Onkologie und Palliativmedizin
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Dresden, Germania, 01307
- Gemeinschaftspraxis Haematologie and Onkologie-Dresden
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Halle, Germania
- Martin-Luther-University Halle-Wittenberg Department of Oncology
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Hanover, Germania
- Medizinische Hochschule
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Heidelberg, Germania
- Universität Heidelberg Medizinische Klinik V Hämatologie, Onkologie und Rheumatologie
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Leverkusen, Germania
- Klinikum Leverkusen
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Ludwigshafen, Germania
- Klinikum Ludwigshafen
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München, Germania
- Rotkreuzklinikum München
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Nuremberg, Germania, 90419
- Klinikum Nürnberg Nord
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Athens, Grecia, 11527
- Hematology Clinic,General Hospital of Athens,G. Gennimatos
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Athens, Grecia, 11527
- National & Kapodistrian University of Athens, Laiko General Hospital
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Athens, Grecia
- Hematology Department Laiko General Hospital
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Athens, Grecia
- Second Depth of Internal Medicine, Attiko University Hospital
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Chaïdári, Grecia, 12462
- National & Kapodistrian University of Athens, Attiko University Hospital
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Ioannina, Grecia, 45110
- Department of clinical hematology ,university hospital Ioannina
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Pátrai, Grecia, 26504
- University of Patras Medical School
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Thessaloniki
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Exochi, Thessaloniki, Grecia
- Haematology Department and HCT Unit G.Papanicolaou Hospital
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New Delhi, India, 110029
- Dr. B.R.A. Institute Rotary Cancer Hospital All India Institute of Medical Sciences
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Bihar
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Patna, Bihar, India, 800014
- Regional Cancer Centre, IGIMS
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Chennai
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Vadapalani, Chennai, India, 600026
- SRM Institutes for Medical Science
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India
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Delhi, India, India, 110029
- IRCH, All India Institute of Medical Sciences
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Kerala
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Thiruvananthapuram, Kerala, India, 695011
- Regional Cancer Centre
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Maharashtra
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Mumbai, Maharashtra, India, 400026
- Jaslok Hospital and Research Centre
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Mumbai, Maharashtra, India, 400010
- Prince Aly Khan Hospital
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Pune, Maharashtra, India, 411004
- Deenanath Mangeshkar Hospital
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National Capital Territory of Delhi
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New Delhi, National Capital Territory of Delhi, India, 110085
- Rajiv Gandhi Cancer Hospital
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Odisha
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Bhubaneswar, Odisha, India, 751003
- Institute of Medical Sciences & SUM Hospital
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Punjab
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Ludhiana, Punjab, India, 160012
- Dayanand Medical College and Hospital
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Tamil Nadu
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Chennai, Tamil Nadu, India, 602105
- Saveetha Medical College Hospital
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Chennai, Tamil Nadu, India, 600020
- Cancer Institute (WIA)
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Coimbatore, Tamil Nadu, India, 641037
- G. Kuppu Swamy Naidu Hospital
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Madurai, Tamil Nadu, India, 625107
- Meenakshi Mission Hospital & Research Centre
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Uttar Pradesh
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Lucknow, Uttar Pradesh, India, 226003
- King George's Medical University (KGMU)
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West Bengal
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Kolkata, West Bengal, India, 700014
- Nil Ratan Sircar Medical College and Hospital
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Kolkata, West Bengal, India, 700094
- Netaji Subhas Chandra Bose Cancer Research Hospital
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Kolkata, West Bengal, India, 700156
- TATA Memorial Centre
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Kolkata, West Bengal, India, 70016
- Netaji Subhas Chandra Bose Cancer Research Institute
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Beersheba, Israele
- Soroka University Medical Center
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Haifa, Israele
- Rambam Healthcare Campus
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Holon, Israele
- Wolfson MC
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Jerusalem, Israele
- Hadassah Medical Center
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Petah Tikva, Israele, 49100
- Rabin Medical Center
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Tel Aviv, Israele, 69710
- Assuta Medical Center
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Tel Aviv, Israele
- Tel Aviv Sourasky Medical Center
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Tel HaShomer, Israele
- Sheba Medical Center
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Bologna, Italia
- Instituto di Ematologia Seragnoli Pad 8 Universita di Bologna
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Florence, Italia, 50134
- SODc Ematologica ,AOU Careggi
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Florence, Italia
- AOU Maggiore della Carità SCDU Ematologia
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Naples, Italia, 80131
- Hematology-Oncology & Stem Cell Transplantation Unit, National Cancer Institute, Fondazione 'G. Pascale', IRCCS
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Novara, Italia, 28100
- SCDU Ematologia, Division of Hematology, Dept. of Translational Medicine, Universita del Piemonte Orientale
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Rome, Italia
- Fondazione Policlinico Universitario A. Gemelli
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Siena, Italia
- Azienda Ospedaliero-Universitaria Senese
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Torino, Italia
- Città della Salute e della Scienza di Torino
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Auckland, Nuova Zelanda, 0622
- North Shore Hospital
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Christchurch, Nuova Zelanda, 8001
- Christchurch Hospital
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Amsterdam, Olanda, 1081 HV
- VUMc (Vrije Universiteit Amsterdam)
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Leiden, Olanda
- LUMC (leidse universitair medisch centrum)
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Gdynia, Polonia, 81-519
- Szpitale Wojewódzkie w Gdyni, Gdyńskie Centrum onkologii
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Krakow, Polonia, 30-510
- MCM (Małopolskie Centrum Medyczne)
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Legnica, Polonia, 59-220
- Wojewodzki Szpital Specjalistyczny w Legnicy
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Lodz, Polonia, 62-1010
- Memorial Provincial Specialist Hospital in Lodz
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Lublin, Polonia
- Hematology Department St John's Cancer Centre
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Olsztyn, Polonia, 10-228
- Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa
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Warsaw, Polonia, 02-776
- Instytut Hematologii i Transfuzjologii
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Warsaw, Polonia, 02-781
- Centrum Onkologii- Insytut Im. Marii Skłodowskiej-Curie Klinika Nowotworow Ukladu Chlonnego
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Warsaw, Polonia
- Maria Sklodowska Curie National Research Institute
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Radeckiego
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Wroclaw, Radeckiego, Polonia, 50-367
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza
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Cambridge, Regno Unito, CB2 0QQ
- Addenbrooke's Hospital Cambridge
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Liverpool, Regno Unito
- Royal Liverpool University Hospital
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Liverpool, Regno Unito
- The Clatterbridge Cancer Centre NHS Foundation Trust
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London, Regno Unito, SE5 9RS
- King's College Hospital
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London, Regno Unito
- Guy's and St Thomas' NHS Foundation Trust
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London, Regno Unito, SE5 9RS
- Princess Royal University Hospital (PRUH)
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Manchester, Regno Unito, M20 4BX
- The Christie NHS Foundation Trust
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Oxford, Regno Unito, OX3 7LE
- Oxford University Hospitals NHS Trust Oxford Cancer and Haematology Centre, Churchill Hospital
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Plymouth, Regno Unito, PL6 8DH
- Derriford Hospital
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Gloucestershire
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Gloucester, Gloucestershire, Regno Unito, GL1 3NN
- Gloucestershire Royal Hospital
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Hampshire
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Southampton, Hampshire, Regno Unito, SO16 6YD
- Southampton University Hospital
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London
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Sutton, London, Regno Unito, SM2 5PT
- Royal Marsden Hospital
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Middlesex
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Harrow, Middlesex, Regno Unito, HA1 3UJ
- Northwick Park Hospital
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Yorkshire
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Leeds, Yorkshire, Regno Unito
- Leeds Teaching Hospitals NHS Trust
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Belgrade, Serbia, 11000
- Kliničko bolnički centar Zvezdara
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Belgrade, Serbia, 11000
- Institut za onkologiju i radiologiju Srbije
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Belgrade, Serbia, 11000
- Klinicko Bolnick Centar Zemun Odeljenje hematologije
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Belgrade, Serbia, 11000
- Klinički centar Srbije Klinika za hematologiju
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Kamenitz, Serbia, 21204
- Institut za onkologiju Vojvodine
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Niš, Serbia, 18000
- Klinički centar Niš Klinika za hematologiju
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Badalona, Spagna, 8916
- Hospitla Universitari Germans Trias i Pujol - ICO
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Barcelona, Spagna
- Hospital Clinic i Provincial de Barcelona
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Barcelona, Spagna, 08035
- Hospital University Vall d'Hebron
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Madrid, Spagna
- Hospital Universitario La Paz
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Palma de Mallorca, Spagna
- Hospital de Son Llàtzer
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Pamplona, Spagna
- Clínica Universidad De Navarra
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Salamanca, Spagna, 37007
- Hospital Universitario de Salamanca
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Seville, Spagna
- Hospital Universitario Virgen del Rocio
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Arizona
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Tucson, Arizona, Stati Uniti, 85704
- UACC Arizona
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California
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San Francisco, California, Stati Uniti
- University of California San Francisco
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Santa Monica, California, Stati Uniti, 90404
- University of California Los Angeles (UCLA)
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Florida
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Plantation, Florida, Stati Uniti
- Boca Raton Cancer Research Medical Center
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Illinois
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Chicago, Illinois, Stati Uniti, 60637
- University of Chicago
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Chicago, Illinois, Stati Uniti
- Robert H. Lurie Comprehensive Cancer Center/Northwestern University
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Kentucky
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Louisville, Kentucky, Stati Uniti, 40241
- Norton Cancer Institute
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Massachusetts
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Boston, Massachusetts, Stati Uniti
- Dana Farber Cancer Institute
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Boston, Massachusetts, Stati Uniti
- Tufts Medical Center
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Burlington, Massachusetts, Stati Uniti
- Lahey Clinic
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Worcester, Massachusetts, Stati Uniti
- University of Massachusetts Medical School
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New Jersey
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Hackensack, New Jersey, Stati Uniti
- John Theurer Cancer Center at Hackensack University Medical Center
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New York
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Lake Success, New York, Stati Uniti
- Clinical Research Alliance
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New York, New York, Stati Uniti, 10065
- New York Presbyterian Hospital/ Cornell Medical College
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Stony Brook, New York, Stati Uniti, 11794
- Stony Brook University Hospital
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Ohio
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Canton, Ohio, Stati Uniti, 44718
- Gabrail Cancer Center
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Cleveland, Ohio, Stati Uniti, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, Stati Uniti
- University Hospitals Seidman Cancer Center
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Oklahoma
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Oklahoma City, Oklahoma, Stati Uniti
- University of Oklahoma
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South Carolina
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Greenville, South Carolina, Stati Uniti, 29605
- Greenville Hospital System
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Texas
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Houston, Texas, Stati Uniti, 77030
- MD Anderson
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Washington
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Seattle, Washington, Stati Uniti, 98104
- Swedish Cancer Institute
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Seattle, Washington, Stati Uniti
- Virginia Mason Hospital & Medical Center
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Budapest, Ungheria, 1083
- Semmelweis Egyetem Általános Orvosi Kar
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Budapest, Ungheria, 1122
- Országos Onkológiai Intézet "A" Belgyógyászati Onkológiai Osztály
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Budapest, Ungheria
- Semmelweis University Department of Medicine and Oncology
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Kaposvár, Ungheria, 7400
- Somogy Megyei Kaposi Mór Oktató Kórház
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Pécs, Ungheria
- Pécsi Tudományegyetem, ÁOK, I. számú Belgyógyászati Klinika
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Veszprém, Ungheria, 8200
- Veszprém Megyei Csolnoky Ferenc Kórház
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Veszprém, Ungheria
- CSolnoky ferenc Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria (Parts 1 and 2):
- Written informed consent in accordance with federal, local, and institutional guidelines. The participant must provide informed consent prior to the first screening procedure.
- Age greater than or equal to (≥) 18 years.
- ECOG performance status of less than or equal to (≤) 2.
- Participants should have estimated life expectancy of greater than (>) 3 months at study entry.
- Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma).
- Participants must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL including (i) at least 1 course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine, or gemcitabine must have been given) and (ii) at least 1 course of anti-CD20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. Participants who were considered ineligible for standard multi-agent immunochemotherapy must have received at least 2 and no more than 5 prior treatment regimens including at least 1 course of anti-CD20 antibodies and must be approved by the Medical Monitor. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy.
- Female participants of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception for 3 months after their last dose of medication. Male participants must use a reliable method of contraception if sexually active with a female of child-bearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose.
Part 1 additional inclusion criteria:
- For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR, at least 60 days must have elapsed since the end of that therapy. For all other participants, at least 14 weeks (98 days) must have elapsed since the end of their most recent systemic anti-DLBCL therapy. . Palliative localized radiation within the therapy-free interval is allowed. Non-chemotherapy maintenance will not be considered anti DLBCL therapy, and therefore is allowed during the therapy-free interval.
- Documented clinical or radiographic evidence of progressive DLBCL prior to dosing.
- Participants must have measurable disease per the revised criteria for response assessment of lymphoma. Lymph nodes should be considered abnormal if the long axis is >1.5 centimeter (cm), regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is >1.0. Lymph nodes ≤1.0 by ≤1.0 will not be considered abnormal for relapse or PD.
Part 2 additional inclusion criteria:
• At least 3 weeks (21 days) must have elapsed since the end of participant's most recent systemic anti-DLBCL therapy (prior to Cycle 1 Day 1). Palliative localized radiation within the therapy-free interval is allowed.Non-chemotherapy maintenance will not be considered anti-DLBCL therapy, and therefore is allowed during the therapy-free interval.
• Adequate hematopoietic function: (i) Hemoglobin ≥10.0 grams per deciliters (g/dL) within 14 days of starting therapy (participant may receive red blood cell [RBC] transfusion within 14 days).
(ii) Absolute neutrophil count ≥1000 cells/millimeter (mm^3) (use of granulocyte growth factors prior to and during the study is acceptable).
(iii) Platelet count ≥100,000/mm^3 within 14 days of starting therapy (use of platelet growth factors prior to and during the study is acceptable).
- Participants must have measurable disease per the revised criteria for response assessment of lymphoma. Lymph nodes should be considered abnormal if the long axis is >1.5 cm, regardless of the short axis. Extranodal lesion should be considered abnormal if the long axis is >1.0 cm.
Exclusion Criteria (Parts 1 and 2):
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Participants who are pregnant or lactating.
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Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
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Participants must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (Investigator must provide detailed documentation for ineligibility).
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Participants who have not recovered to Grade ≤1 clinically significant adverse events, or to their baseline, from their most recent systemic anti-DLBCL therapy.
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Major surgery within 2 weeks of first dose of study treatment.
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Participants with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections.
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Psychiatric illness or substance use that would prevent the participant from giving informed consent or being compliant with the study procedures.
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Any of the following laboratory abnormalities:
(i) A circulating lymphocyte count of >50,000/L. (ii) Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome: total bilirubin of >3*ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 times ULN. In participants with known liver involvement of their DLBCL, AST and ALT >5*ULN.
(iii) Severe renal dysfunction: estimated creatinine clearance of <30 mL/min, measured in 24-hour urine or calculated using the formula of Cockroft and Gault [(140-Age)*Mass (kg)/(72*creatinine mg/dL); multiply by 0.85 if female].
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety.
- Participants with active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation.
- Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals on Cycle 1 Day 1; however, prophylactic use of these agents is acceptable even if parenteral.
- Participants unable to swallow tablets, participants with malabsorption syndrome, or any other gastrointestinal disease or gastrointestinal dysfunction that could interfere with absorption of study treatment.
Part 1 additional exclusion criteria:
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For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR: Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids <60 days or <14 weeks prior to Cycle 1 Day 1.
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Known central nervous system lymphoma or meningeal involvement.
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DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, composite lymphoma (Hodgkin's lymphoma+NHL), or DLBCL transformed from diseases other than indolent NHL.
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Unstable cardiovascular function:
(i) Symptomatic ischemia, or (ii) Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block /right bundle branch block will not be excluded), or (iii) Congestive heart failure of New York Heart Association Class ≥3, or (iv) Myocardial infarction within 3 months.
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Participants with a BSA <1.4 m^2 as calculated per Dubois 1916 or Mosteller 1987.
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Any of the following laboratory abnormalities:
(i) Absolute neutrophil count (ANC) <1000 cells/mm^3 or platelet count <75,000/mm^3 during screening and on Cycle 1 Day 1. Use of granulocyte-stimulating factors and platelet growth factors prior to and during the study is acceptable.
(ii) Hematopoietic dysfunction: hemoglobin < 10.0 g/dL within 14 days of and including Cycle 1 Day 1 and/or patients receiving red blood cell (RBC) transfusion within 14 days of and including Cycle 1 Day 1.
- Participants who have been committed to an institution by official or judicial order.
- Participants with dependency on the Sponsor, Investigator or study site.
Part 2 additional exclusion criteria:
- Participants with active HBV, HVC, or HIV infections. Participants with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units per milliliters (IU/mL) prior to first dose of study treatment. Participants with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Participants with HIV who have CD4+T-cell counts ≥350 cells/microliter (mcL), negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year are allowed.
- Known active central nervous system lymphoma or meningeal involvement. Participants with a history of CNS disease treated into remission may be enrolled.
- DLBCL with MALT lymphoma, composite lymphoma (Hodgkin's lymphoma + NHL), DLBCL arising from CLL (Richter's transformation), or high-grade B-cell lymphoma.
- Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosing or strong CYP3A inducers ≤14 days prior to Day 1 dosing.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Part 1: Selinexor 60 mg
Participants received fixed dose of 60 mg selinexor orally, twice weekly (BIW) on Days 1 and 3 (e.g., Monday and Wednesday or Tuesday and Thursday, etc.) of Weeks 1-4 of each four week (each cycle of 28 days) cycle (total of 8 doses per cycle). |
Dose: 60 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
Dose: 40 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
Dose: 60 mg (BIW) and 60 mg (QW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
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Sperimentale: Part 2: Arm A-Selinexor 40 mg
Participants received selinexor 40 mg orally BIW on Days 1 and 3 of each week of 4-week treatment cycles (28 days) until disease progression (total of 8 doses per cycle). |
Dose: 60 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
Dose: 40 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
Dose: 60 mg (BIW) and 60 mg (QW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
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Sperimentale: Part 2: Arm B-Selinexor 60 mg
Participants received selinexor 60 mg orally BIW on Days 1 and 3 of each week of 4-week treatment cycles) for 2 cycles (each cycle of 28 days) followed by 60 mg once weekly (QW) in the subsequent cycles until disease progression (total of 8 doses per cycle). |
Dose: 60 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
Dose: 40 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
Dose: 60 mg (BIW) and 60 mg (QW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Part 1: Overall Response Rate (ORR)
Lasso di tempo: One year
|
Assessed according to the revised response criteria based on the Guidelines of the International Working Group (IWG). |
One year
|
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Part 2: Overall Response Rate (ORR) Based on Lugano Criteria
Lasso di tempo: From initial randomization until date of disease progression or death (maximum of 1 year from Part 2 randomization)
|
Assessed according to the response assessment of lymphoma based on Lugano classification. |
From initial randomization until date of disease progression or death (maximum of 1 year from Part 2 randomization)
|
Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
|
Parte 1: Durata della risposta (DOR)
Lasso di tempo: Dal momento della prima risposta fino alla progressione della malattia o al decesso (massimo 1 anno dalla randomizzazione Parte 1)
|
Dal momento della prima risposta fino alla progressione della malattia o al decesso (massimo 1 anno dalla randomizzazione Parte 1)
|
|
Parte 1: tasso di controllo delle malattie (DCR)
Lasso di tempo: Dalla risposta iniziale fino alla progressione della malattia o alla morte (massimo 1 anno dalla randomizzazione Parte 1)
|
Dalla risposta iniziale fino alla progressione della malattia o alla morte (massimo 1 anno dalla randomizzazione Parte 1)
|
|
Parte 1: Numero di partecipanti con eventi avversi emergenti dal trattamento (TEAE)
Lasso di tempo: Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 1)
|
Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 1)
|
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Parte 1: Numero di partecipanti con Performance Status dell'Eastern Cooperative Oncology Group (ECOG).
Lasso di tempo: Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 1)
|
Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 1)
|
|
Parte 2: Durata della risposta (DOR)
Lasso di tempo: Dal momento della prima risposta (Parte 2) fino alla progressione della malattia o al decesso (massimo 1 anno dalla randomizzazione della Parte 2)
|
Dal momento della prima risposta (Parte 2) fino alla progressione della malattia o al decesso (massimo 1 anno dalla randomizzazione della Parte 2)
|
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Parte 2: tasso di controllo delle malattie (DCR)
Lasso di tempo: Dalla risposta iniziale (Parte 2) fino alla progressione della malattia o al decesso (massimo 1 anno dalla randomizzazione della Parte 2)
|
Dalla risposta iniziale (Parte 2) fino alla progressione della malattia o al decesso (massimo 1 anno dalla randomizzazione della Parte 2)
|
|
Parte 2: tasso di risposta globale (ORR) basato sui criteri di Lugano modificati
Lasso di tempo: Dalla randomizzazione iniziale fino alla data della progressione della malattia o del decesso (massimo 1 anno dalla randomizzazione della Parte 2)
|
Dalla randomizzazione iniziale fino alla data della progressione della malattia o del decesso (massimo 1 anno dalla randomizzazione della Parte 2)
|
|
Parte 2: Numero di partecipanti con eventi avversi emergenti dal trattamento
Lasso di tempo: Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 2)
|
Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 2)
|
|
Parte 2: Numero di partecipanti con Performance Status dell'Eastern Cooperative Oncology Group (ECOG).
Lasso di tempo: Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 2)
|
Dal basale fino a 30 giorni dopo l'ultima dose (massimo 1 anno dalla randomizzazione Parte 2)
|
Collaboratori e investigatori
Sponsor
Pubblicazioni e link utili
Pubblicazioni generali
- Schuster M, Zijlstra J, Casasnovas RO, Vermaat JSP, Kalakonda N, Goy A, Choquet S, Neste EVD, Hill B, Thieblemont C, Cavallo F, De la Cruz F, Kuruvilla J, Hamad N, Jaeger U, Caimi P, Gurion R, Warzocha K, Bakhshi S, Sancho JM, Follows G, Egyed M, Offner F, Vassilakopoulos T, Samal P, Ku M, Ma X, Corona K, Chamoun K, Shah J, Shacham S, Kauffman MG, Canales M, Maerevoet M. Effect of Prior Therapy and Disease Refractoriness on the Efficacy and Safety of Oral Selinexor in Patients with Diffuse Large B-cell Lymphoma (DLBCL): A Post-hoc Analysis of the SADAL Study. Clin Lymphoma Myeloma Leuk. 2022 Jul;22(7):483-494. doi: 10.1016/j.clml.2021.12.016. Epub 2021 Dec 25.
- Maerevoet M, Zijlstra JM, Follows G, Casasnovas RO, Vermaat JSP, Kalakonda N, Goy A, Choquet S, Van Den Neste E, Hill B, Thieblemont C, Cavallo F, De la Cruz F, Kuruvilla J, Hamad N, Jaeger U, Caimi P, Gurion R, Warzocha K, Bakhshi S, Sancho JM, Schuster M, Egyed M, Offner F, Vassilakopoulos TP, Samal P, Ku M, Ma X, Corona K, Chamoun K, Shah J, Shacham S, Kauffman MG, Canales M. Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study. J Hematol Oncol. 2021 Jul 16;14(1):111. doi: 10.1186/s13045-021-01122-1.
- Shah J, Shacham S, Kauffman M, Daniele P, Tomaras D, Tremblay G, Casasnovas RO, Maerevoet M, Zijlstra J, Follows G, P Vermaat JS, Kalakonda N, Goy AH, Choquet S, Den Neste EV, Hill BT, Thieblemont C, Cavallo F, la Cruz F, Kuruvilla J, Hamad N, Bouabdallah R, Jager U, Caimi P, Gurion R, Warzocha K, Bakhshi S, Sancho JM, Schuster M, Egyed M, Offner F, Vasilakopoulos TP, Samal P, Nagy A, Ku M, Canales Albendea MA. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma. Future Oncol. 2021 Apr;17(11):1295-1310. doi: 10.2217/fon-2020-0946. Epub 2021 Feb 2.
- Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, Casasnovas O, Hamad N, Zijlstra JM, Bakhshi S, Bouabdallah R, Choquet S, Gurion R, Hill B, Jaeger U, Sancho JM, Schuster M, Thieblemont C, De la Cruz F, Egyed M, Mishra S, Offner F, Vassilakopoulos TP, Warzocha K, McCarthy D, Ma X, Corona K, Saint-Martin JR, Chang H, Landesman Y, Joshi A, Wang H, Shah J, Shacham S, Kauffman M, Van Den Neste E, Canales MA. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020 Jul;7(7):e511-e522. doi: 10.1016/S2352-3026(20)30120-4.
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Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stimato)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- KCP-330-009
- 2014-001977-15 (Numero EudraCT)
- 2014 (Sovvenzione/contratto NIH degli Stati Uniti)
Piano per i dati dei singoli partecipanti (IPD)
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Informazioni su farmaci e dispositivi, documenti di studio
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Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .