Hematologic Neoplasms, Immunogenicity, Influenza
Conditions
Brief summary
This randomized controlled trial evaluates and compares the immunogenicity of three different influenza vaccine formulations: high-dose trivalent (HD-IIV3), MF59-adjuvanted quadrivalent (aIIV4), and standard-dose trivalent (SD-IIV3) vaccines. The study population consists of patients with hematologic malignancies, including those undergoing autologous stem cell transplantation or CAR-T cell therapy. The primary goal is to identify which vaccine strategy elicits the most robust antibody and T cell-mediated immune responses in this severely immunocompromised population
Detailed description
Patients with hematologic malignancies face a 3-10 times higher risk of influenza infection and a 5-20 times greater rate of severe complications compared to the general population, owing to disease- and treatment-related immunosuppression. Although high-dose and adjuvanted influenza vaccines have been proposed to overcome suboptimal vaccine responses in this population, robust comparative evidence remains lacking - particularly following recent clinical trials which did not demonstrate superiority of adjuvanted vaccine over standard-dose vaccine in terms of antibody response. Critically, T cell-mediated immune responses, which may serve as an independent correlate of protection especially in B cell-depleted patients (e.g., post-CAR-T therapy), have not been comprehensively evaluated in prior trials. This randomized controlled trial aims to compare the immunogenicity of three influenza vaccine formulations - high-dose trivalent inactivated vaccine (HD-IIV3; Efluelda), MF59-adjuvanted quadrivalent inactivated vaccine (aIIV4; Fluad Quadrivalent), and standard-dose trivalent inactivated vaccine (SD-IIV3) - in patients with hematologic malignancies including lymphoma, leukemia, plasma cell disorders, and those undergoing autologous stem cell transplantation or CAR-T cell therapy. Immunogenicity will be assessed by both antibody responses (HAI-based GMT, seroconversion, seroprotection) and cellular immune responses (polyfunctional CD4+ and cytotoxic CD8+ T cells via IFN-γ/TNF-α/IL-2 intracellular cytokine staining of PBMCs) at baseline, Day 28, Day 180, and Day 365.
Interventions
BIOLOGICALHigh-dose trivalent inactivated influenza vaccine (HD-IIV3)
High-dose trivalent inactivated influenza vaccine containing 60 µg hemagglutinin per strain (4× standard dose). Single intramuscular injection administered during the influenza season.
BIOLOGICALMF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4)
MF59C.1 squalene-based adjuvanted quadrivalent inactivated influenza vaccine containing 15 µg hemagglutinin per strain. Single intramuscular injection administered during the influenza season.
BIOLOGICALStandard-dose trivalent inactivated influenza vaccine (SD-IIV3)
Standard-dose trivalent inactivated influenza vaccine containing 15 µg hemagglutinin per strain. Single intramuscular injection administered during the influenza season. Active comparator.
Sponsors
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged 19 years or older * Confirmed diagnosis of hematologic malignancy, including: non-Hodgkin lymphoma, Hodgkin lymphoma, acute leukemia, chronic leukemia, or plasma cell disorders
Exclusion criteria
* Difficulty with repeated venipuncture or blood sampling (e.g., poor vascular access or bleeding tendency) * Cognitive or psychiatric impairment precluding understanding of or cooperation with study procedures * Known hypersensitivity to influenza vaccine components * Influenza vaccination within the preceding 6 months * Any other condition deemed clinically inappropriate for study participation at investigator discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion rate at Day 28 post-vaccination | Day 28 (±7 days) post-vaccination | Proportion of participants achieving ≥4-fold rise in hemagglutinin inhibition (HAI) titer from baseline at Day 28, compared among HD-IIV3, aIIV4, and SD-IIV3 arms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Other Immunogenicity | Day 28 (±7 days), Day 180(±30 days), and Day 365(±30 days) post-vaccination | 1. Humoral Immune Response (Antibody Response) Geometric Mean Titer (GMT): Measured by Hemagglutination Inhibition (HAI) assay. Geometric Mean Fold Rise (GMFR): Ratio of post-vaccination to pre-vaccination HAI titer. Seroprotection Rate: Proportion of participants achieving an HAI titer of ≥ 1:40. 2. Cellular Immune Response T-cell Functionality: Quantification of IFN-γ, TNF-α, and IL-2 expression in CD4+ and CD8+ T cells from peripheral blood mononuclear cells (PBMCs). |
Countries
South Korea
Contacts
CONTACTSo Yun Lim, MD, PhD
CONTACTSung-Han Kim, MD, PhD
PRINCIPAL_INVESTIGATORSung-Han Kim, MD, PhD
Asan Medical Center
Outcome results
None listed