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| Name | Class |
|---|---|
| The University of Hong Kong | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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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| 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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| 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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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD-1/PD-L1 inhibitors | Drug | Including nivolumab, pembrolizumab, atezolizumab, and durvalumab, et al. |
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| Measure | Description | Time Frame |
|---|---|---|
| Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM) | 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) | 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) | 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) | 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) | 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 | Titer of neutralization antibody is measured by neutralization test. | Day 0 after vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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NSCLC patients receiving PD-1/PD-L1 inhibitors during this project
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yayi He | Contact | 8613818828623 | 2250601@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Yayi He, PhD, MD | Shanghai Pulmonary Hospital, Shanghai, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong | Hong Kong | Hong Kong | China |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D000082082 | Immune Checkpoint Inhibitors |
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
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Biospecimen includes the peripheral blood samples collected on day0, 12h, day1, 2, 7, 21, 30, 60 and 6 months after vaccination.
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| Inactivated trivalent influenza vaccine | Biological | Including two type A viruses, H1N1 and H3N2, and one type B virus, B/Brisbane. |
|
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| Titer of neutralization antibody | Titer of neutralization antibody is measured by neutralization test. | Day 21 after vaccination |
| Titer of neutralization antibody | Titer of neutralization antibody is measured by neutralization test. | Day 30 after vaccination |
| Titer of neutralization antibody | Titer of neutralization antibody is measured by neutralization test. | Day 60 after vaccination |
| Titer of neutralization antibody | Titer of neutralization antibody is measured by neutralization test. | Month 6 after vaccination |
| Multiple chemokine and cytokine levels in peripheral blood | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) |
| Disease Control Rate (DCR) |
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) | 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) |
| Shanghai Pulmonary Hospital | Shanghai | Shanghai Municipality | 200433 | China |
|
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |