Impact of Inactivated Trivalent Influenza Vaccine on NSCLC Patients Receiving PD-1 / PD-L1 Inhibitors
20 de abril de 2020 actualizado por: Caicun Zhou, Shanghai Pulmonary Hospital, Shanghai, China
A Cohort Study to Evaluate the Impact of Inactivated Trivalent Influenza Vaccine on the Immunogenicity, Safety and Survival of Non-small Cell Lung Cancer Patients Receiving PD-1 / PD-L1 Inhibitors
This project is to assess the immunogenicity, safety and overall survival impact of intramuscular injection of trivalent influenza vaccine in non-small cell lung cancer (NSCLC) patients with PD-1/PD-L1 inhibitor treatment.
Descripción general del estudio
Estado
Aún no reclutando
Intervención / Tratamiento
Descripción detallada
Lung cancer is one of the most prevalent cancers in the world. Among them, non-small cell lung cancer (NSCLC) accounts for about 85%. Immune checkpoint inhibitors such as programmed death 1(PD-1) and PD-L1 are new treatments for NSCLC. About 290,000 to 650,000 people die from respiratory illnesses caused by seasonal flu all over the world. Cancer patients are one of the high-risk groups of influenza. Although the United States, Britain, Australia have issued guidelines recommending that cancer patients be vaccinated against influenza every year, due to concerns about the immune effect and safety of flu vaccination for cancer patients, multiple countries including China have not included cancer patients into priority influenza vaccination populations. Therefore, how to further prove the immunogenicity and safety of influenza vaccine in NSCLC patients is the key to promote influenza vaccines in NSCLC patients.
This study will recruit 130 patients with NSCLC who have been treated with PD-1 / PD-L1 inhibitors for 6 months or more and 30 healthy participants. Among them, 100 NSCLC patients and 30 healthy participants will be intramuscularly inactivated with a trivalent influenza vaccine during the influenza seasons 2020-21 and 2021-22. Vaccinated participants' peripheral blood samples were collected at day0, 12 hours, day1, 2, 7, 21, 30, 60 and 6 months after vaccination. The influenza specific antibody titers, inflammatory chemokines and cytokines, antibody-dependent cellular cytotoxicity (ADCC) activity, T lymphocytes activity and the proportions of different T cells subgroups will be measured to evaluate the participants' immune response to the vaccine. In addition, for the subjects receiving the vaccine, the study will also group by age to compare the differences in immune effects between subjects aged 18-65 and subjects over 65.
At last, this project will compare immune-related adverse events (irAEs) that occurred after receiving PD-1 / PD-L1 inhibitor therapy and survival time between NSCLC patients who receive influenza vaccine and those who do not receive influenza vaccine.
Tipo de estudio
De observación
Inscripción (Anticipado)
160
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Yayi He
- Número de teléfono: 8613818828623
- Correo electrónico: 2250601@qq.com
Ubicaciones de estudio
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Hong Kong
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Hong Kong, Hong Kong, Porcelana
- School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong
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Contacto:
- Lit Man Leo Poon, PhD.
- Número de teléfono: 852-3917 9943
- Correo electrónico: llmpoon@hkucc.hku.hk
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Shanghai
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Shanghai, Shanghai, Porcelana, 200433
- Shanghai Pulmonary Hospital
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Contacto:
- Yayi He
- Número de teléfono: 8613818828623
- Correo electrónico: 2250601@qq.com
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Investigador principal:
- Yayi He, PhD, MD
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra de probabilidad
Población de estudio
NSCLC patients receiving PD-1/PD-L1 inhibitors during this project
Descripción
Inclusion Criteria:
- NSCLC patients were diagnosed with clear pathological classification and receive PD-1 / PD-L1 inhibitor treatment during this project.
- NSCLC patients have the exact start and end time of PD-1 / PD-L1 inhibitor and / or the vaccination time and follow-up information.
- The healthy participants are not in an immunosuppressive state, such as cancer, HIV, autoimmune diseases, and long-term use of immunosuppressive drugs.
- The healthy participants have exact vaccination time.
- All participants have complete clinical and laboratory diagnostic data.
- All participants are 18-75 years, regardless of gender.
- All participants have agreed and signed the consent form before enrollment.
Exclusion Criteria:
- Patients with unclear diagnosis of lung cancer were excluded.
- Patients with incomplete clinical data or incomplete follow-up records.
- Patients without signed informed consent.
- Patient has received blood transfusion within three months.
- Patients with HIV, Hepatitis B and Hepatitis C infections.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: Grupo
- Perspectivas temporales: Futuro
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
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Vaccinated NSCLC group
This group contains 100 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
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Including nivolumab, pembrolizumab, atezolizumab, and durvalumab, et al.
Otros nombres:
Including two type A viruses, H1N1 and H3N2, and one type B virus, B/Brisbane.
Otros nombres:
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Vaccinated Health group
This group contains 30 healthy participants without immunosuppressive diseases, who will be intramuscularly injected one dose of inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
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Including two type A viruses, H1N1 and H3N2, and one type B virus, B/Brisbane.
Otros nombres:
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Unvaccinated NSCLC group
This group contains 30 NSCLC patients receiving PD-1/PD-L1 inhibitors for more than 6 months without intramuscular injection of any inactivated trivalent influenza vaccine in influenza seasons 2020-21 or 2021-22 (November-May).
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Including nivolumab, pembrolizumab, atezolizumab, and durvalumab, et al.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
Periodo de tiempo: Day 0 after vaccination
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The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
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Day 0 after vaccination
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Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
Periodo de tiempo: Day 2 after vaccination
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The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
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Day 2 after vaccination
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Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
Periodo de tiempo: Day 7 after vaccination
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The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
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Day 7 after vaccination
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Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
Periodo de tiempo: Day 21 after vaccination
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The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
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Day 21 after vaccination
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Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
Periodo de tiempo: Day 30 after vaccination
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The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
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Day 30 after vaccination
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Titer of neutralization antibody
Periodo de tiempo: Day 0 after vaccination
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Titer of neutralization antibody is measured by neutralization test.
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Day 0 after vaccination
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Titer of neutralization antibody
Periodo de tiempo: Day 21 after vaccination
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Titer of neutralization antibody is measured by neutralization test.
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Day 21 after vaccination
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Titer of neutralization antibody
Periodo de tiempo: Day 30 after vaccination
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Titer of neutralization antibody is measured by neutralization test.
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Day 30 after vaccination
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Titer of neutralization antibody
Periodo de tiempo: Day 60 after vaccination
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Titer of neutralization antibody is measured by neutralization test.
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Day 60 after vaccination
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Titer of neutralization antibody
Periodo de tiempo: Month 6 after vaccination
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Titer of neutralization antibody is measured by neutralization test.
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Month 6 after vaccination
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Multiple chemokine and cytokine levels in peripheral blood
Periodo de tiempo: Day 0 after vaccination
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IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.
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Day 0 after vaccination
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Multiple chemokine and cytokine levels in peripheral blood
Periodo de tiempo: 12 hours after vaccination
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IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.
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12 hours after vaccination
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Multiple chemokine and cytokine levels in peripheral blood
Periodo de tiempo: Day 1 after vaccination
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IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.
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Day 1 after vaccination
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Multiple chemokine and cytokine levels in peripheral blood
Periodo de tiempo: Day 2 after vaccination
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IFN-γ, IL-1β, IL-2,IL-3,IL-4,IL-5,IL-6,IL-8 (CXCL8),IL-9,IL-10,IL-11,IL-12,IL-13,GM-CSF,TNF-α, IP-10 (CXCL10), MCP-1 (CCL2), and TARC (CCL17) in peripheral blood are measured by cytometry bead assay.
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Day 2 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 0 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 0 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: 12 hours after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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12 hours after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 1 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 1 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 2 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 2 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 7 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 7 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 21 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 21 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 30 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 30 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Day 60 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Day 60 after vaccination
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The numbers and proportions of T lymphocyte subpopulations in peripheral blood
Periodo de tiempo: Month 6 after vaccination
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The numbers and proportions of CD4+ T cells, CD8+ T cells, naïve T cells and effector memory T cells in peripheral blood are measured by multiple flow cytometry.
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Month 6 after vaccination
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Peripheral T cell activation and proliferation
Periodo de tiempo: Day 0 after vaccination
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The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.
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Day 0 after vaccination
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Peripheral T cell activation and proliferation
Periodo de tiempo: Day 30 after vaccination
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The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.
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Day 30 after vaccination
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Peripheral T cell activation and proliferation
Periodo de tiempo: Day 60 after vaccination
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The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.
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Day 60 after vaccination
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Peripheral T cell activation and proliferation
Periodo de tiempo: Month 6 after vaccination
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The CD3, CD4, CD8 and CD69 expressions and cell count of peripheral T cells are measured by multiple flow cytometry upon carboxyfluorescein succinimidyl amino ester (CFSE) labeling and anti-CD3/28 beads activation.
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Month 6 after vaccination
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Antibody-dependent cellular cytotoxicity (ADCC)
Periodo de tiempo: Day 0 after vaccination
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The ADCC activities of NK-92 cells cultured by the sera from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.
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Day 0 after vaccination
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Antibody-dependent cellular cytotoxicity (ADCC)
Periodo de tiempo: Day 30 after vaccination
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The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.
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Day 30 after vaccination
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Antibody-dependent cellular cytotoxicity (ADCC)
Periodo de tiempo: Day 60 after vaccination
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The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.
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Day 60 after vaccination
|
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Antibody-dependent cellular cytotoxicity (ADCC)
Periodo de tiempo: Month 6 after vaccination
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The ADCC activities of NK-92 cells cultured by the sera collected from vaccinated participants are measured by lactic acid dehydrogenase (LDH) release of A549 cells infected by H1N1 and H3N2.
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Month 6 after vaccination
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Immune-related adverse events (irAEs)
Periodo de tiempo: June 2020- June 2023
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The performances and the grades of irAEs according to Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0) and their correlation with vaccination.
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June 2020- June 2023
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Progression-free Survival (PFS)
Periodo de tiempo: June 2020- June 2023 (3 year)
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PFS is calculated as the time from from PD-1/PD-L1 inhibitor starting to the disease progression or the death from any cause.
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June 2020- June 2023 (3 year)
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Overall Survival (OS)
Periodo de tiempo: June 2020- June 2023 (3 year)
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OS is calculated as the time from PD-1/PD-L1 inhibitor starting to the death from any cause.
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June 2020- June 2023 (3 year)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Objective Response Rate (ORR)
Periodo de tiempo: June 2020- June 2023 (3 year)
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The proportion of patients whose tumors have shrunk to a certain amount and maintained for a certain period of time, including cases of complete response (CR) and partial response (PR) according to Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1).
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June 2020- June 2023 (3 year)
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Disease Control Rate (DCR)
Periodo de tiempo: June 2020- June 2023 (3 year)
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The proportion of patients achieve CR or PR or stable disease (SD) after PD-1/PD-L1 inhibitor treatment according to RECIST 1.1.
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June 2020- June 2023 (3 year)
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Time to Treatment Failure (TFF)
Periodo de tiempo: June 2020- June 2023 (3 year)
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The time from the start of PD-1/PD-L1 inhibitor to the withdrawal of the trial.
The reasons for withdrawal include the patient's voluntary withdrawal, disease progression, adverse events and even deaths.
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June 2020- June 2023 (3 year)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Yayi He, PhD, MD, Shanghai Pulmonary Hospital, Shanghai, China
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Anticipado)
1 de junio de 2020
Finalización primaria (Anticipado)
31 de diciembre de 2022
Finalización del estudio (Anticipado)
31 de mayo de 2023
Fechas de registro del estudio
Enviado por primera vez
9 de abril de 2020
Primero enviado que cumplió con los criterios de control de calidad
20 de abril de 2020
Publicado por primera vez (Actual)
21 de abril de 2020
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
21 de abril de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
20 de abril de 2020
Última verificación
1 de abril de 2020
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones por virus de ARN
- Enfermedades virales
- Infecciones
- Infecciones del Tracto Respiratorio
- Enfermedades de las vías respiratorias
- Neoplasias
- Enfermedades pulmonares
- Neoplasias por sitio
- Neoplasias de las vías respiratorias
- Neoplasias torácicas
- Carcinoma Broncogénico
- Neoplasias Bronquiales
- Infecciones por Orthomyxoviridae
- Neoplasias Pulmonares
- Carcinoma de pulmón de células no pequeñas
- Influenza Humana
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antineoplásicos
- Factores inmunológicos
- Anticuerpos
- Vacunas
- Inmunoglobulinas
- Anticuerpos Monoclonales
- Agentes antineoplásicos inmunológicos
- Inhibidores de puntos de control inmunitarios
Otros números de identificación del estudio
- TIV-NSCLC-PD1
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Indeciso
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .