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Impact of Inactivated Trivalent Influenza Vaccine on NSCLC Patients Receiving PD-1 / PD-L1 Inhibitors

2020年4月20日 更新者：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.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

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.

研究类型

观察性的

注册 (预期的)

160

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

  • 姓名：Yayi He
  • 电话号码：8613818828623
  • 邮箱：2250601@qq.com

学习地点

  • 中国
    • Hong Kong
      • Hong Kong、Hong Kong、中国
        • School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong
        • 接触：
    • Shanghai
      • Shanghai、Shanghai、中国、200433
        • Shanghai Pulmonary Hospital
        • 接触：
        • 首席研究员：
          • Yayi He, PhD, MD

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 75年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

取样方法

概率样本

研究人群

NSCLC patients receiving PD-1/PD-L1 inhibitors during this project

描述

Inclusion Criteria:

  1. NSCLC patients were diagnosed with clear pathological classification and receive PD-1 / PD-L1 inhibitor treatment during this project.
  2. NSCLC patients have the exact start and end time of PD-1 / PD-L1 inhibitor and / or the vaccination time and follow-up information.
  3. The healthy participants are not in an immunosuppressive state, such as cancer, HIV, autoimmune diseases, and long-term use of immunosuppressive drugs.
  4. The healthy participants have exact vaccination time.
  5. All participants have complete clinical and laboratory diagnostic data.
  6. All participants are 18-75 years, regardless of gender.
  7. All participants have agreed and signed the consent form before enrollment.

Exclusion Criteria:

  1. Patients with unclear diagnosis of lung cancer were excluded.
  2. Patients with incomplete clinical data or incomplete follow-up records.
  3. Patients without signed informed consent.
  4. Patient has received blood transfusion within three months.
  5. Patients with HIV, Hepatitis B and Hepatitis C infections.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 观测模型：队列
  • 时间观点：预期

队列和干预

团体/队列
干预/治疗
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).
药品：PD-1/PD-L1 inhibitors
Including nivolumab, pembrolizumab, atezolizumab, and durvalumab, et al.
其他名称：
  • PD-1/PD-L1 blockades
  • PD-1 monoclonal antibodies
  • PD-L1 monoclonal antibodies
生物：Inactivated trivalent influenza vaccine
Including two type A viruses, H1N1 and H3N2, and one type B virus, B/Brisbane.
其他名称：
  • Flu Vaccines
  • Influenza Virus Vaccines
  • Influenza Vaccine, Trivalent
  • Vaccine, Trivalent Influenza
  • Flu Shot
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).
生物：Inactivated trivalent influenza vaccine
Including two type A viruses, H1N1 and H3N2, and one type B virus, B/Brisbane.
其他名称：
  • Flu Vaccines
  • Influenza Virus Vaccines
  • Influenza Vaccine, Trivalent
  • Vaccine, Trivalent Influenza
  • Flu Shot
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).
药品：PD-1/PD-L1 inhibitors
Including nivolumab, pembrolizumab, atezolizumab, and durvalumab, et al.
其他名称：
  • PD-1/PD-L1 blockades
  • PD-1 monoclonal antibodies
  • PD-L1 monoclonal antibodies

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
大体时间：Day 0 after vaccination
The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
Day 0 after vaccination
Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
大体时间：Day 2 after vaccination
The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
Day 2 after vaccination
Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
大体时间：Day 7 after vaccination
The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
Day 7 after vaccination
Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
大体时间：Day 21 after vaccination
The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
Day 21 after vaccination
Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
大体时间：Day 30 after vaccination
The titers of anti-HA IgG and IgM antibodies ,and anti-NP IgG and IgM antibodies are measured by enzyme linked immunosorbent assay (ELISA).
Day 30 after vaccination
Titer of neutralization antibody
大体时间：Day 0 after vaccination
Titer of neutralization antibody is measured by neutralization test.
Day 0 after vaccination
Titer of neutralization antibody
大体时间：Day 21 after vaccination
Titer of neutralization antibody is measured by neutralization test.
Day 21 after vaccination
Titer of neutralization antibody
大体时间：Day 30 after vaccination
Titer of neutralization antibody is measured by neutralization test.
Day 30 after vaccination
Titer of neutralization antibody
大体时间：Day 60 after vaccination
Titer of neutralization antibody is measured by neutralization test.
Day 60 after vaccination
Titer of neutralization antibody
大体时间：Month 6 after vaccination
Titer of neutralization antibody is measured by neutralization test.
Month 6 after vaccination
Multiple chemokine and cytokine levels in peripheral blood
大体时间：Day 0 after vaccination
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.
Day 0 after vaccination
Multiple chemokine and cytokine levels in peripheral blood
大体时间：12 hours after vaccination
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.
12 hours after vaccination
Multiple chemokine and cytokine levels in peripheral blood
大体时间：Day 1 after vaccination
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.
Day 1 after vaccination
Multiple chemokine and cytokine levels in peripheral blood
大体时间：Day 2 after vaccination
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.
Day 2 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 0 after vaccination
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.
Day 0 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：12 hours after vaccination
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.
12 hours after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 1 after vaccination
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.
Day 1 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 2 after vaccination
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.
Day 2 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 7 after vaccination
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.
Day 7 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 21 after vaccination
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.
Day 21 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 30 after vaccination
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.
Day 30 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Day 60 after vaccination
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.
Day 60 after vaccination
The numbers and proportions of T lymphocyte subpopulations in peripheral blood
大体时间：Month 6 after vaccination
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.
Month 6 after vaccination
Peripheral T cell activation and proliferation
大体时间：Day 0 after vaccination
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.
Day 0 after vaccination
Peripheral T cell activation and proliferation
大体时间：Day 30 after vaccination
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.
Day 30 after vaccination
Peripheral T cell activation and proliferation
大体时间：Day 60 after vaccination
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.
Day 60 after vaccination
Peripheral T cell activation and proliferation
大体时间：Month 6 after vaccination
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.
Month 6 after vaccination
Antibody-dependent cellular cytotoxicity (ADCC)
大体时间：Day 0 after vaccination
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.
Day 0 after vaccination
Antibody-dependent cellular cytotoxicity (ADCC)
大体时间：Day 30 after vaccination
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.
Day 30 after vaccination
Antibody-dependent cellular cytotoxicity (ADCC)
大体时间：Day 60 after vaccination
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.
Day 60 after vaccination
Antibody-dependent cellular cytotoxicity (ADCC)
大体时间：Month 6 after vaccination
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.
Month 6 after vaccination
Immune-related adverse events (irAEs)
大体时间：June 2020- June 2023
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.
June 2020- June 2023
Progression-free Survival (PFS)
大体时间：June 2020- June 2023 (3 year)
PFS is calculated as the time from from PD-1/PD-L1 inhibitor starting to the disease progression or the death from any cause.
June 2020- June 2023 (3 year)
Overall Survival (OS)
大体时间：June 2020- June 2023 (3 year)
OS is calculated as the time from PD-1/PD-L1 inhibitor starting to the death from any cause.
June 2020- June 2023 (3 year)

次要结果测量

结果测量
措施说明
大体时间
Objective Response Rate (ORR)
大体时间：June 2020- June 2023 (3 year)
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).
June 2020- June 2023 (3 year)
Disease Control Rate (DCR)
大体时间：June 2020- June 2023 (3 year)
The proportion of patients achieve CR or PR or stable disease (SD) after PD-1/PD-L1 inhibitor treatment according to RECIST 1.1.
June 2020- June 2023 (3 year)
Time to Treatment Failure (TFF)
大体时间：June 2020- June 2023 (3 year)
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.
June 2020- June 2023 (3 year)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Shanghai Pulmonary Hospital, Shanghai, China

合作者

The University of Hong Kong

调查人员

  • 首席研究员：Yayi He, PhD, MD、Shanghai Pulmonary Hospital, Shanghai, China

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (预期的)

2020年6月1日

初级完成 (预期的)

2022年12月31日

研究完成 (预期的)

2023年5月31日

研究注册日期

首次提交

2020年4月9日

首先提交符合 QC 标准的

2020年4月20日

首次发布 (实际的)

2020年4月21日

研究记录更新

最后更新发布 (实际的)

2020年4月21日

上次提交的符合 QC 标准的更新

2020年4月20日

最后验证

2020年4月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • TIV-NSCLC-PD1

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

未定

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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