Clinical trial NCT04355806: Impact of Inactivated Trivalent Influenza Vaccine on NSCLC Patients Receiving PD-1 / PD-L1 Inhibitors
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Non Small Cell Lung Cancer
Influenza Vaccine
Keywords: Non-Small Cell Lung Cancer
Influenza Vaccine
PD-1 Receptor
Programmed Cell Death 1 Ligand 1
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
Collaborators: name: The University of Hong Kong
First posted: 2020-04-21
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: NSCLC patients receiving PD-1/PD-L1 inhibitors during this project

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
timeFrame: Day 0 after vaccination
measure: Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
timeFrame: Day 2 after vaccination
measure: Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
timeFrame: Day 7 after vaccination
measure: Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
timeFrame: Day 21 after vaccination
measure: Titers of anti-nucleoprotein(NP) or anti-hemagglutinin(HA) antibody (IgG and IgM)
timeFrame: Day 30 after vaccination
measure: Titer of neutralization antibody
timeFrame: Day 0 after vaccination
measure: Titer of neutralization antibody
timeFrame: Day 21 after vaccination
measure: Titer of neutralization antibody
timeFrame: Day 30 after vaccination
measure: Titer of neutralization antibody
timeFrame: Day 60 after vaccination
measure: Titer of neutralization antibody
timeFrame: Month 6 after vaccination
measure: Multiple chemokine and cytokine levels in peripheral blood
timeFrame: Day 0 after vaccination
measure: Multiple chemokine and cytokine levels in peripheral blood
timeFrame: 12 hours after vaccination
measure: Multiple chemokine and cytokine levels in peripheral blood
timeFrame: Day 1 after vaccination
measure: Multiple chemokine and cytokine levels in peripheral blood
timeFrame: Day 2 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 0 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: 12 hours after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 1 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 2 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 7 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 21 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 30 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Day 60 after vaccination
measure: The numbers and proportions of T lymphocyte subpopulations in peripheral blood
timeFrame: Month 6 after vaccination
measure: Peripheral T cell activation and proliferation
timeFrame: Day 0 after vaccination
measure: Peripheral T cell activation and proliferation
timeFrame: Day 30 after vaccination
measure: Peripheral T cell activation and proliferation
timeFrame: Day 60 after vaccination
measure: Peripheral T cell activation and proliferation
timeFrame: Month 6 after vaccination
measure: Antibody-dependent cellular cytotoxicity (ADCC)
timeFrame: Day 0 after vaccination
measure: Antibody-dependent cellular cytotoxicity (ADCC)
timeFrame: Day 30 after vaccination
measure: Antibody-dependent cellular cytotoxicity (ADCC)
timeFrame: Day 60 after vaccination
measure: Antibody-dependent cellular cytotoxicity (ADCC)
timeFrame: Month 6 after vaccination
measure: Immune-related adverse events (irAEs)
timeFrame: June 2020- June 2023
measure: Progression-free Survival (PFS)
timeFrame: June 2020- June 2023 (3 year)
measure: Overall Survival (OS)
timeFrame: June 2020- June 2023 (3 year)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: June 2020- June 2023 (3 year)
measure: Disease Control Rate (DCR)
timeFrame: June 2020- June 2023 (3 year)
measure: Time to Treatment Failure (TFF)
timeFrame: June 2020- June 2023 (3 year)
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong
state: Hong Kong
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Pulmonary Hospital, Shanghai, China
name: Yayi He, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: