MEDI4736 Alone and in Combination With Tremelimumab or AZD9150 in Adult Subjects With Relapsed/Refractory DLBCL (D4190C00023)
26 de fevereiro de 2019 atualizado por: 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Intervencional
Inscrição (Real)
32
Estágio
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
-
-
California
-
La Jolla, California, Estados Unidos, 92093
- Research Site
-
-
Maryland
-
Baltimore, Maryland, Estados Unidos, 21201
- Research Site
-
-
New Mexico
-
Albuquerque, New Mexico, Estados Unidos, 87131
- Research Site
-
-
North Carolina
-
Durham, North Carolina, Estados Unidos, 27710
- Research Site
-
-
South Carolina
-
Charleston, South Carolina, Estados Unidos, 29425
- Research Site
-
-
Texas
-
Dallas, Texas, Estados Unidos, 75390
- Research Site
-
Houston, Texas, Estados Unidos, 77030
- Research Site
-
-
Wisconsin
-
Milwaukee, Wisconsin, Estados Unidos, 53226
- Research Site
-
-
-
-
-
Marseille, França, 13273
- Research Site
-
Villejuif, França, 94805
- Research Site
-
-
-
-
-
Dublin 8, Irlanda
- Research Site
-
Galway, Irlanda
- Research Site
-
-
-
-
-
Leicester, Reino Unido, LE1 5WW
- Research Site
-
-
Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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)
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: MEDI4736
|
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
|
|
Experimental: MEDI4736 and tremelimumab
|
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
|
|
Experimental: MEDI4736 and AZD9150
|
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events
Prazo: Screening through 90 days after the last dose of study medication
|
Screening through 90 days after the last dose of study medication
|
|
|
Number of subjects experiencing dose-limiting toxicities
Prazo: 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
|
Changes from baseline in laboratory parameters, vital signs, and ECGs
|
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
|
Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
|
Number of subjects who develop anti-drug antibodies (ADA)
Prazo: Screening through 90 days after last dose of study medication
|
Screening through 90 days after last dose of study medication
|
|
Time to Response
Prazo: Screening though 3 years after the last subject receives the first dose of study medication
|
Screening though 3 years after the last subject receives the first dose of study medication
|
|
Duration of Response
Prazo: Screening though 3 years after the last subject receives the first dose of study medication
|
Screening though 3 years after the last subject receives the first dose of study medication
|
|
Progression Free survival
Prazo: Screening though 3 years after the last subject receives the first dose of study medication
|
Screening though 3 years after the last subject receives the first dose of study medication
|
|
Time to progression
Prazo: Screening though 3 years after the last subject receives the first dose of study medication
|
Screening though 3 years after the last subject receives the first dose of study medication
|
|
Event free survival
Prazo: Screening though 3 years after the last subject receives the first dose of study medication
|
Screening though 3 years after the last subject receives the first dose of study medication
|
|
Overall survival
Prazo: Screening though 3 years after the last subject receives the first dose of study medication
|
Screening though 3 years after the last subject receives the first dose of study medication
|
|
MEDI4736 Maximum Plasma Concentration (Cmax)
Prazo: Measured at defined study visits from time of first dose through end of treatment
|
Measured at defined study visits from time of first dose through end of treatment
|
|
Tremelimumab Maximum Plasma Concentration (Cmax)
Prazo: Measured at defined study visits from time of first dose through end of treatment
|
Measured at defined study visits from time of first dose through end of treatment
|
|
AZD9150 Maximum Plasma Concentration (Cmax)
Prazo: Measured at defined study visits from time of first dose through end of treatment
|
Measured at defined study visits from time of first dose through end of treatment
|
|
MEDI4736 Minimum Plasma Concentration (Cmin)
Prazo: Measured at defined study visits from time of first dose through end of treatment
|
Measured at defined study visits from time of first dose through end of treatment
|
|
Tremelimumab Minimum Plasma Concentration (Cmin)
Prazo: Measured at defined study visits from time of first dose through end of treatment
|
Measured at defined study visits from time of first dose through end of treatment
|
|
AZD9150 Minimum Plasma Concentration (Cmin)
Prazo: Measured at defined study visits from time of first dose through end of treatment
|
Measured at defined study visits from time of first dose through end of treatment
|
|
Individual MEDI4736 Concentrations
Prazo: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
|
Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
|
|
Individual tremelimumab Concentrations
Prazo: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
|
Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
|
|
Individual AZD9150 Concentrations
Prazo: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
|
Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
|
|
Change from baseline of STAT3 RNA (signal transducer and activator of transcription)
Prazo: Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
|
Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
|
|
Baseline PD-L1 protein expression within the tumor
Prazo: Measured on tumor samples provided at screening
|
Measured on tumor samples provided at screening
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
13 de julho de 2016
Conclusão Primária (Real)
4 de fevereiro de 2019
Conclusão do estudo (Real)
4 de fevereiro de 2019
Datas de inscrição no estudo
Enviado pela primeira vez
27 de agosto de 2015
Enviado pela primeira vez que atendeu aos critérios de CQ
11 de setembro de 2015
Primeira postagem (Estimativa)
15 de setembro de 2015
Atualizações de registro de estudo
Última Atualização Postada (Real)
27 de fevereiro de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
26 de fevereiro de 2019
Última verificação
1 de fevereiro de 2019
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do sistema imunológico
- Neoplasias por Tipo Histológico
- Neoplasias
- Distúrbios Linfoproliferativos
- Doenças Linfáticas
- Distúrbios imunoproliferativos
- Linfoma Não-Hodgkin
- Linfoma
- Linfoma de Células B
- Linfoma de Células B Grandes Difuso
- Agentes Antineoplásicos
- Agentes Antineoplásicos Imunológicos
- Durvalumabe
- Tremelimumabe
Outros números de identificação do estudo
- D4190C00023
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .