MEDI4736 Alone and in Combination With Tremelimumab or AZD9150 in Adult Subjects With Relapsed/Refractory DLBCL (D4190C00023)
26 februari 2019 bijgewerkt door: MedImmune LLC
A Phase 1b Study to Evaluate the Safety and Efficacy of MEDI4736 as Monotherapy and in Combination With Tremelimumab or AZD9150 in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma.
The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This is a multicenter, open-label, dose-escalation and dose-expansion study of MEDI4736 (durvalumab) as monotherapy or in combination with either tremelimumab or AZD9150.
The objectives are to describe any dose-limiting toxicities, determine the maximum tolerated dose, and evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics of MEDI4736 as monotherapy or in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
32
Fase
- Fase 1
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Marseille, Frankrijk, 13273
- Research Site
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Villejuif, Frankrijk, 94805
- Research Site
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Dublin 8, Ierland
- Research Site
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Galway, Ierland
- Research Site
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Leicester, Verenigd Koninkrijk, LE1 5WW
- Research Site
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California
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La Jolla, California, Verenigde Staten, 92093
- Research Site
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21201
- Research Site
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New Mexico
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Albuquerque, New Mexico, Verenigde Staten, 87131
- Research Site
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North Carolina
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Durham, North Carolina, Verenigde Staten, 27710
- Research Site
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South Carolina
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Charleston, South Carolina, Verenigde Staten, 29425
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Texas
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Dallas, Texas, Verenigde Staten, 75390
- Research Site
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Houston, Texas, Verenigde Staten, 77030
- Research Site
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Wisconsin
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Milwaukee, Wisconsin, Verenigde Staten, 53226
- Research Site
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Age ≥ 18 years
- Subjects with histologically confirmed relapsed or refractory DLBCL who have received at least 1 prior rituximab containing chemotherapy regimen but no more than 5 prior lines of therapy
- Eastern Cooperative Group (ECOG) performance status of 0 or 1
- Measurable disease by International Working Group (IWG) response criteria for lymphoma
- Adequate organ and marrow function
Exclusion Criteria:
- Previous immune-mediated therapy
- Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.
- Documented current central nervous system involvement
3. Active or prior documented autoimmune or inflammatory disease within 3 years, with some exceptions 4. Concurrent or prior conventional or investigational anticancer therapy, within 28 days prior to the first dose of study medication(s)
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: MEDI4736
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MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
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Experimenteel: MEDI4736 and tremelimumab
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MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion
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Experimenteel: MEDI4736 and AZD9150
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MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events
Tijdsspanne: Screening through 90 days after the last dose of study medication
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Screening through 90 days after the last dose of study medication
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Number of subjects experiencing dose-limiting toxicities
Tijdsspanne: First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150
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Changes from baseline in laboratory parameters, vital signs, and ECGs
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First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
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Number of subjects who develop anti-drug antibodies (ADA)
Tijdsspanne: Screening through 90 days after last dose of study medication
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Screening through 90 days after last dose of study medication
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Time to Response
Tijdsspanne: Screening though 3 years after the last subject receives the first dose of study medication
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Screening though 3 years after the last subject receives the first dose of study medication
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Duration of Response
Tijdsspanne: Screening though 3 years after the last subject receives the first dose of study medication
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Screening though 3 years after the last subject receives the first dose of study medication
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Progression Free survival
Tijdsspanne: Screening though 3 years after the last subject receives the first dose of study medication
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Screening though 3 years after the last subject receives the first dose of study medication
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Time to progression
Tijdsspanne: Screening though 3 years after the last subject receives the first dose of study medication
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Screening though 3 years after the last subject receives the first dose of study medication
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Event free survival
Tijdsspanne: Screening though 3 years after the last subject receives the first dose of study medication
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Screening though 3 years after the last subject receives the first dose of study medication
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Overall survival
Tijdsspanne: Screening though 3 years after the last subject receives the first dose of study medication
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Screening though 3 years after the last subject receives the first dose of study medication
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MEDI4736 Maximum Plasma Concentration (Cmax)
Tijdsspanne: Measured at defined study visits from time of first dose through end of treatment
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Measured at defined study visits from time of first dose through end of treatment
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Tremelimumab Maximum Plasma Concentration (Cmax)
Tijdsspanne: Measured at defined study visits from time of first dose through end of treatment
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Measured at defined study visits from time of first dose through end of treatment
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AZD9150 Maximum Plasma Concentration (Cmax)
Tijdsspanne: Measured at defined study visits from time of first dose through end of treatment
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Measured at defined study visits from time of first dose through end of treatment
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MEDI4736 Minimum Plasma Concentration (Cmin)
Tijdsspanne: Measured at defined study visits from time of first dose through end of treatment
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Measured at defined study visits from time of first dose through end of treatment
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Tremelimumab Minimum Plasma Concentration (Cmin)
Tijdsspanne: Measured at defined study visits from time of first dose through end of treatment
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Measured at defined study visits from time of first dose through end of treatment
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AZD9150 Minimum Plasma Concentration (Cmin)
Tijdsspanne: Measured at defined study visits from time of first dose through end of treatment
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Measured at defined study visits from time of first dose through end of treatment
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Individual MEDI4736 Concentrations
Tijdsspanne: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
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Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
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Individual tremelimumab Concentrations
Tijdsspanne: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
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Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
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Individual AZD9150 Concentrations
Tijdsspanne: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
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Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
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Change from baseline of STAT3 RNA (signal transducer and activator of transcription)
Tijdsspanne: Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
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Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
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Baseline PD-L1 protein expression within the tumor
Tijdsspanne: Measured on tumor samples provided at screening
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Measured on tumor samples provided at screening
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
13 juli 2016
Primaire voltooiing (Werkelijk)
4 februari 2019
Studie voltooiing (Werkelijk)
4 februari 2019
Studieregistratiedata
Eerst ingediend
27 augustus 2015
Eerst ingediend dat voldeed aan de QC-criteria
11 september 2015
Eerst geplaatst (Schatting)
15 september 2015
Updates van studierecords
Laatste update geplaatst (Werkelijk)
27 februari 2019
Laatste update ingediend die voldeed aan QC-criteria
26 februari 2019
Laatst geverifieerd
1 februari 2019
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Lymfatische ziekten
- Immunoproliferatieve aandoeningen
- Lymfoom, non-Hodgkin
- Lymfoom
- Lymfoom, B-cel
- Lymfoom, grote B-cel, diffuus
- Antineoplastische middelen
- Antineoplastische middelen, immunologisch
- Durvalumab
- Tremelimumab
Andere studie-ID-nummers
- D4190C00023
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Ja
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .