Influenza Vaccination in Patients Receiving Immune Checkpoint Inhibitor

Study Overview
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Brief Summary
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The purpose of this study is to elucidate efficacy and safety of influenza vaccine in cancer patients receiving immune checkpoint inhibitor.

Detailed Description
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Solid cancer patients receiving immune checkpoint inhibitor or cytotoxic chemotherapy will be recruited 1:2 manner in two hospitals. Target numbers are 48 and 95, respectively. All the participants will be vaccinated for influenza during their chemotherapy when they meet inclusion criteria. All the participants will be asked if they have any contraindication for influenza vaccine by a physician before vaccination. Hemagglutination inhibition Ab titre at pre-vaccination and post-vaccination (21-35 days after vaccination) will be examined in all participants to examine seroprotection rates, seroconversion rates, and changes in geometric mean titer. And they will be monitored for any vaccination-related adverse reaction or immune-related adverse events after 2-4 days(via phone call), and till 6 months after vaccination (when they visit oncology clinics).

Official Title
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Efficacy and Safety of Influenza Vaccine in Cancer Patients Receiving Immune Checkpoint Inhibitor

Conditions
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Influenza, Solid Carcinoma

Intervention / Treatment
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* Biological: Influenza vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Solid cancer patients receiving immune checkpoint inhibitor or cytotoxic chemotherapeutic agent in Seoul National University Hospital or Seoul National University Bundang Hospital. Patients who was not vaccinated for influenza in 2018-2019 season ECOG performance status 0 or 1 Patients who fulfilling following laboratory criteria Total bilirubin ≤ 1.5 x upper normal limit Aspartate transaminase, alanine transaminase ≤ 2.5 x upper normal limit Alkaline phosphatase ≤ 2.5 x upper normal limit Creatinine ≤ upper normal limit Patients who can understand and agreed with the informed consents. Exclusion Criteria: Patients having contraindication for influenza vaccination (e.g. egg allergy) Patients who receive any immunosuppressant (excluding steroid for anti-emetic effect) Patients with HIV infection Patients with autoimmune disease who are anticipated to have a problem with immunogenicity for vaccine Patients who have transplanted organ and receive immunosuppressants Patients who are suspected to have active infection (e.g. pneumonia) Patients who receive targeted chemotherapeutic agent alone for cancer treatment Patients who could not receive cancer chemotherapy due to hematologic abnormality at the date of the participation

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double center prospective case-control clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immune checkpoint inhibitor<br>Solid cancer patients who receiving immune checkpoint inhibitor patients will be undergone Influenza vaccination using purified inactivated influenza virus antigen (Green Cross Corp.) 0.5 mL IM once | Biological: Influenza vaccination<br>* Purified inactivated influenza virus antigen (Green Cross Corp) 0.5 mL once IM<br>|
| Active Comparator: Cytotoxic chemotherapy<br>Solid cancer patients who receiving conventional cytotoxic chemotherapy will be undergone Influenza vaccination using purified inactivated influenza virus antigen (Green Cross Corp.) 0.5 mL IM once | Biological: Influenza vaccination<br>* Purified inactivated influenza virus antigen (Green Cross Corp) 0.5 mL once IM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection rate | The percentage of vaccine recipients with a serum haemagglutination inhibition(HI) titre ≥40 post vaccination (21-28 days) | 21 to 35 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate | Seroconversion rate is defined as the percentage of vaccine recipients with a fourfold increase or more in post-vaccination HI titre | 21 to 35 days after vaccination | 
| Geometric mean titer of HI | Geometric mean titers of HI (haemagglutination inhibition) after vaccination | 21 to 35 days after vaccination | 
| Injection-related adverse events | The proportion of patients who experienced local or systemic adverse events related to vaccination | 21 to 35 days after vaccination | 
| Immune-related adverse events | The proportion of patients who experienced immune checkpoint inhibitor induced immune-related adverse events | 6 months after vaccination | 
| T-cell mediated immune response | The levels of intracellular cytokines measured by flow cytometry | 21 to 35 days after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, vaccine, solid carcinoma, immune checkpoint, efficacy, safety