Influenza Vaccination Strategy for Patients With Hematologic Malignancy ((HEM-FLU))

March 20, 2026 updated by: Sung-Han Kim, Asan Medical Center

Comparison of Immunogenicity of Different Influenza Vaccines in Patients With Hematologic Malignancies

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard dose Influenza vaccine
Biological: Standard-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.
Experimental: High dose influenza vaccine
Biological: High-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.
Experimental: MF.59 adjuvant influenza vaccine
Biological: MF59-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Seroconversion rate at Day 28 post-vaccination
Time Frame: 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
Day 28 (±7 days) post-vaccination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Other Immunogenicity
Time Frame: 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).
Day 28 (±7 days), Day 180(±30 days), and Day 365(±30 days) post-vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Investigators

  • Principal Investigator: Sung-Han Kim, MD, PhD, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 4, 2025

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

April 30, 2028

Study Registration Dates

First Submitted

March 17, 2026

First Submitted That Met QC Criteria

March 17, 2026

First Posted (Actual)

March 20, 2026

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-1450
  • RS-2025-25468314 (Other Grant/Funding Number: Ministry of health and welfare, South Korea)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared publicly to protect patient privacy and confidentiality, in strict accordance with the Institutional Review Board (IRB) approval conditions for this trial.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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