Linvolseltamab (bispecifická protilátka anti-BCMA x anti-CD3) plus další léčba rakoviny pro účastníky s relapsem/refrakterním mnohočetným myelomem (LINKER-MM2)
Studie fáze 1b REGN5458 (bispecifická protilátka anti-BCMA x anti-CD3) plus další léčba rakoviny u pacientů s relapsem/refrakterním mnohočetným myelomem
This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again.
In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies).
This study is the first time linvoseltamab will be combined with other cancer therapies.
The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination.
The study is looking at several other research questions, including:
- How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma
- What side effects may happen from taking linvoseltamab together with another cancer treatment
- How much study drug is in the blood at different times
- Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)
Přehled studie
Postavení
Podmínky
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Clinical Trials Administrator
- Telefonní číslo: 844-734-6643
- E-mail: clinicaltrials@regeneron.com
Studijní místa
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Angers, Francie, 49933
- Nábor
- Centre Hospitalier Universitaire Angers
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Montpellier, Francie, 34295
- Nábor
- CHU Montpellier - Departement D'Hematologie
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Paris, Francie, 75571
- Nábor
- Saint Antoine Hospital
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Villejuif, Francie, 94805
- Nábor
- Institut Gustave Roussy
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New Aquitaine
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Poitiers, New Aquitaine, Francie, 86021
- Nábor
- Centre Hospitalier Universitaire (CHU) de Poitiers
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Nord
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Lille, Nord, Francie, 59037
- Nábor
- CHU de Lille - Rue Michel Polonovski
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Pays de la Loire Region
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Nantes, Pays de la Loire Region, Francie, 44093
- Nábor
- Nantes University Hospital
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Île-de-France Region
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Créteil, Île-de-France Region, Francie, 94000
- Nábor
- Hospital Henri Mondor
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Paris, Île-de-France Region, Francie, 75015
- Nábor
- Hopital Necker
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Paris, Île-de-France Region, Francie, 75010
- Nábor
- Saint Louis Hospital
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Haifa, Izrael, 3109601
- Nábor
- Rambam Health Care Campus
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Jerusalem, Izrael, 91120
- Nábor
- Hadassah Medical Center
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Central District
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Ramat Gan, Central District, Izrael, 5265601
- Nábor
- Sheba Medical Center
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California
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La Jolla, California, Spojené státy, 92037
- Nábor
- Scripps Clinic Torrey Pines
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Georgia
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Atlanta, Georgia, Spojené státy, 30004
- Nábor
- Winship Cancer Institute of Emory University
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Indiana
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Indianapolis, Indiana, Spojené státy, 46202
- Nábor
- Indiana University Health Simon Cancer Center
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02215
- Nábor
- Dana Farber/Harvard Cancer Center
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Michigan
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Detroit, Michigan, Spojené státy, 48201
- Nábor
- Karmanos Cancer Institute
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Minnesota
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Rochester, Minnesota, Spojené státy, 55905
- Nábor
- Mayo Clinic
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New York
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New York, New York, Spojené státy, 10021
- Nábor
- Weill Cornell Medicine/New York Presbyterian Hospital
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New York, New York, Spojené státy, 10032
- Nábor
- New York Presbyterian Hospital Columbia University Medical Center
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North Carolina
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Chapel Hill, North Carolina, Spojené státy, 27599
- Nábor
- University of North Carolina at Chapel Hill
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Winston-Salem, North Carolina, Spojené státy, 27157
- Nábor
- Wake Forest University Health Sciences
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Ohio
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Columbus, Ohio, Spojené státy, 43210
- Nábor
- The Ohio State University James Cancer Hospital
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Texas
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Dallas, Texas, Spojené státy, 75390
- Nábor
- University of Texas Southwestern
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Washington
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Seattle, Washington, Spojené státy, 98108
- Nábor
- VA Puget Sound Health Care System
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Athens, Řecko, 11528
- Nábor
- General Hospital of Athens Alexandra
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Attica
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Athens, Attica, Řecko, 10676
- Nábor
- Evangelismos General Hospital
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Barcelona, Španělsko, 08035
- Nábor
- Hospital Universitario Vall d'Hebron
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Barcelona, Španělsko, 08036
- Nábor
- Hospital Clinic de Barcelona
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Barcelona, Španělsko, 08908
- Nábor
- Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals,
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Madrid, Španělsko, 28050
- Nábor
- Hospital Universitario HM Sanchinarro
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Madrid, Španělsko, 28027
- Nábor
- Clinica Universidad de Navarra - Madrid
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Madrid, Španělsko, 28006
- Nábor
- Universitaru Hospital La Princesa
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Madrid, Španělsko, 28041
- Nábor
- University Hospital and Research Institute
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Madrid, Španělsko, 28034
- Nábor
- Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria
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Salamanca, Španělsko, 37007
- Nábor
- University Hospital of Salamanca
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A Coruna
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Santiago de Compostela, A Coruna, Španělsko, 15706
- Nábor
- Hospital Clinico Universitario de Santiago
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Barcelona
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Badalona, Barcelona, Španělsko, 08916
- Nábor
- Hospital Germans Trias i Pujol
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Cantabria
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Santander, Cantabria, Španělsko, 39008
- Nábor
- Hospital Universitario Marques de Valdecilla
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Madrid
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Pozuelo de Alarcón, Madrid, Španělsko, 28223
- Nábor
- Hospital Universitario Quiron Salud Madrid
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Navarre
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Pamplona, Navarre, Španělsko, 31008
- Nábor
- Clinica Universidad de Navarra
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
General Key Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- Participants must have measurable disease as defined in the protocol according to IMWG consensus criteria
- Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol
- Life expectancy of at least 6 months
Cohort Specific Inclusion Criteria:
For cohorts 1-6, each participant must have RRMM with progression following at least 3 lines of therapy, or at least 2 lines of therapy and either prior exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD) and 1 Proteasome Inhibitor (PI), or double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated, as described in the protocol Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated, as described in the protocol
Cohort 7 and 8:
- For participants without measurable disease by biochemical parameters [serum or urine M-protein, or serum involved Free Light Chain (FLC)], presence of at least 1 soft tissue plasmacytoma with a single diameter of ≥2 cm
- RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI or triple-class refractory disease (anti-CD38 antibody, IMiD, PI) Cohort 9: Progressive RRMM in participants with triple-class refractory disease (anti-CD38 antibody, IMiD, PI) after at least 3 lines of therapy Cohort 10: Progressive RRMM after at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI
General Key Exclusion Criteria:
- Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes)
- Participants with known MM brain lesions or meningeal involvement
- Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter
- History of allogeneic and autologous stem cell transplantation, as described in the protocol
- Unless stated otherwise in a specific sub-protocol, prior treatment with a T cell-based immunotherapy directed against B-Cell Maturation Antigen (BCMA) bispecific antibodies and Bispecific T-cell Engagers (BiTEs), and BCMA Chimeric Antigen Receptor (CAR) T cells (Note: BCMA antibody-drug conjugates are not excluded)
- History of progressive multifocal leukoencephalopathy, neurodegenerative condition or Central Nervous System (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded
- Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential
- Cardiac ejection fraction <40% by Echocardiogram (Echo) or Multigated Acquisition (MUGA) scan
Cohort Specific Exclusion Criteria:
Cohort 2: Dose expansion: Prior treatment with a BCMA-directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment Cohort 3: Known malabsorption syndrome or pre-existing gastrointestinal (GI) condition that may impair absorption of lenalidomide; delivery of lenalidomide via nasogastric tube or gastrostomy tube is not allowed Cohort 4: Peripheral neuropathy grade ≥2 Cohort 5: Known malabsorption syndrome or pre-existing GI conditions that may impair absorption of pomalidomide; delivery of pomalidomide via nasogastric tube or gastrostomy tube is not allowed
Cohort 7:
- Prior treatment with anti-Lymphocyte Activation Gene 3 (LAG-3) agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Programmed cell Death Protein 1 (PD-1) antibodies is permitted, as described in the protocol
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol
- Prior solid organ transplant
- History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies
Cohort 8:
- Prior treatment with anti-PD-1 or anti-PD-L1 agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) antibodies is permitted, as described in the protocol
- Encephalitis or meningitis in the year prior to enrollment
- History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol.
- Prior solid organ transplant
- History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies
Cohort 9:
- Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol
- Use of concomitant medications that are known to prolong the QT/QTcF interval including Class Ia and Class III antiarrhythmics at the time of informed consent
- Ongoing use or anticipated use of food or drugs that are known strong/moderate cytochrome P450 (CYP)3A4 inhibitors, or strong CYP3A inducers within 14 days prior to first dose of nirogacestat
- Known malabsorption syndrome or existing gastrointestinal GI condition that may impair absorption of nirogacestat; delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed
Cohort 10:
- Known or suspected active Epstein-Barr Virus (EBV) infection
- Known history of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)
- Prior treatment with cevostamab or another agent with the same target [Fragment crystallizable Receptor-like 5 (FcRH5)]
Dose finding portion: Prior treatment with any BCMA-directed immunotherapy will not be exclusionary, as described in the protocol Dose expansion portion: Prior treatment with any T cell-engaging bispecific antibody directed against BCMA will be exclusionary, as described in the protocol
NOTE: Other protocol defined inclusion/exclusion criteria apply
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Cohort 1: Linvoseltamab + Daratumumab
Linvoseltamab + Daratumumab |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 2: Linvoseltamab + Carfilzomib
Linvoseltamab + Carfilzomib |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 3: Linvoseltamab + Lenalidomide
Linvoseltamab + Lenalidomide |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 4: Linvoseltamab + Bortezomib
Linvoseltamab + Bortezomib |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 5: Linvoseltamab + Pomalidomide
Linvoseltamab + Pomalidomide |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 6: Linvoseltamab + Isatuximab
Linvoseltamab + Isatuximab |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 7: Linvoseltamab + Fianlimab
Linvoseltamab + Fianlimab |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 8: Linvoseltamab + Cemiplimab
Linvoseltamab + Cemiplimab |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 9: Linvoseltamab + Nirogacestat
Linvoseltamab + Nirogacestat |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
|
Experimentální: Cohort 10: Linvoseltamab + Cevostamab
Linvoseltamab + Cevostamab |
Administered per the protocol
Ostatní jména:
Administered per the protocol
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Výskyt závažných nežádoucích příhod (SAE)
Časové okno: Až 5 let
|
Až 5 let
|
|
|
Závažnost TEAE
Časové okno: Až 5 let
|
Až 5 let
|
|
|
Závažnost SAE
Časové okno: Až 5 let
|
Až 5 let
|
|
|
Závažnost AESI
Časové okno: Až 5 let
|
Až 5 let
|
|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Časové okno: Up to 5 Years
|
Up to 5 Years
|
|
|
Incidence of Adverse Events of Special Interest (AESIs)
Časové okno: Up to 5 Years
|
Up to 5 Years
|
|
|
Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period
Časové okno: Up to 28 Days
|
Dose finding portion only |
Up to 28 Days
|
|
Incidence of laboratory abnormalities
Časové okno: Up to 5 Years
|
≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0] |
Up to 5 Years
|
Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
|
Celkové přežití (OS)
Časové okno: Až 5 let
|
Až 5 let
|
|
Koncentrace celkového linvoseltamabu v séru v průběhu času
Časové okno: Až 5 let
|
Až 5 let
|
|
Overall Response Rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria
Časové okno: Up to 5 Years
|
Up to 5 Years
|
|
Duration of Response (DOR) by IMWG criteria
Časové okno: Up to 5 Years
|
Up to 5 Years
|
|
Progression-Free Survival (PFS) as measured by IMWG criteria
Časové okno: Up to 5 Years
|
Up to 5 Years
|
|
Rate of Minimal Residual Disease (MRD) negative status by IMWG criteria
Časové okno: Up to 5 Years
|
Up to 5 Years
|
|
Incidence over time of Anti-Drug Antibodies (ADAs) to linvoseltamab
Časové okno: Up to 5 Years
|
Up to 5 Years
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: Clinical Trial Management, Regeneron Pharmaceuticals
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Cévní onemocnění
- Kardiovaskulární choroby
- Novotvary
- Onemocnění imunitního systému
- Novotvary podle histologického typu
- Hematologická onemocnění
- Lymfoproliferativní poruchy
- Imunoproliferativní poruchy
- Novotvary, plazmatické buňky
- Hemostatické poruchy
- Paraproteinémie
- Poruchy krevních bílkovin
- Hemoragické poruchy
- Hemická a lymfatická onemocnění
- Mnohočetný myelom
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Karboxylové kyseliny
- Piperidiny
- Anorganické chemikálie
- Kyseliny boronové
- Kyseliny, nekarboxylové
- Kyseliny
- Boronové sloučeniny
- Pyraziny
- Fthalimidy
- Kyseliny ftalové
- Kyseliny, karbocyklické
- Piperidony
- Isoindoly
- Lenalidomid
- Bortezomib
- Carfilzomib
- Pomalidomid
- daratumumab
- CEMIPLIMAB
- Isatuximab
- Nirogacestat
Další identifikační čísla studie
- R5458-ONC-2012
- 2020-004638-39 (Číslo EudraCT)
- 2023 (Grant/smlouva NIH USA)
- 2023-506247-42-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Časový rámec sdílení IPD
When Regeneron has:
- received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
- made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
- the legal authority to share the data, and
- ensured the ability to protect participant privacy
Kritéria přístupu pro sdílení IPD
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
- ANALYTIC_CODE
- CSR
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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