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AzTrials

Hematologic NeoplasmsPhase 3(HEM-FLU)NCT07485855

Influenza Vaccination Strategy for Patients With Hematologic Malignancy

A Phase 3 study testing High-dose trivalent inactivated influenza vaccine (HD-IIV3), MF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4) and Standard-dose trivalent inactivated influenza vaccine (SD-IIV3) in people with Hematologic Neoplasms and Influenza, run by Asan Medical Center at 1 site in South Korea.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Hematologic Neoplasms, Influenza, Immunogenicity
What is being tested?
High-dose trivalent inactivated influenza vaccine (HD-IIV3), MF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4) and Standard-dose trivalent inactivated influenza vaccine (SD-IIV3)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteSouth Korea
Study dates
4 Dec 2025to 30 Apr 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

So Yun Lim, MD, PhD contact

+82-10-4120-3816

soyun_lim@amc.seoul.kr

Sung-Han Kim, MD, PhD contact

+82-2-3010-3305

shkimmd@amc.seoul.kr

South Korea1 site, 1 recruiting

  • Asan Medical Center

    Seoul

    So Yun Lim, MD, PhD, +82-2-3010-3303, soyun_lim@amc.seoul.kr

    Recruiting

Other trials in South Korea

About this study

Official title: 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

Read the 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.

Being tested
High-dose trivalent inactivated influenza vaccine (HD-IIV3), MF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4), Standard-dose trivalent inactivated influenza vaccine (SD-IIV3)
Medical subject headings
Hematologic Neoplasms, Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • High-dose trivalent inactivated influenza vaccine (HD-IIV3)Biological

    High-dose trivalent inactivated influenza vaccine containing 60 µg hemagglutinin per strain (4× standard dose). Single intramuscular injection administered during the influenza season.

  • MF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4)Biological

    MF59C.1 squalene-based adjuvanted quadrivalent inactivated influenza vaccine containing 15 µg hemagglutinin per strain. Single intramuscular injection administered during the influenza season.

  • Standard-dose trivalent inactivated influenza vaccine (SD-IIV3)Biological

    Standard-dose trivalent inactivated influenza vaccine containing 15 µg hemagglutinin per strain. Single intramuscular injection administered during the influenza season. Active comparator.

Study groups in NCT07485855
Study groupRoleWhat they receive
Standard dose Influenza vaccineActive comparatorStandard dose Influenza vaccine
Receives: Biological: Standard-dose trivalent inactivated influenza vaccine (SD-IIV3)
High dose influenza vaccineExperimentalHigh dose influenza vaccine
Receives: Biological: High-dose trivalent inactivated influenza vaccine (HD-IIV3)
MF.59 adjuvant influenza vaccineExperimentalMF.59 adjuvant influenza vaccine
Receives: Biological: MF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Seroconversion rate at Day 28 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

    Measured: Day 28 (±7 days) post-vaccination

Secondary outcomes (1)

  1. Other Immunogenicity

    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).

    Measured: Day 28 (±7 days), Day 180(±30 days), and Day 365(±30 days) post-vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2026
  2. Study start4 Dec 2025
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07485855
Sponsor's protocol ID
2025-1450
Other IDs
RS-2025-25468314
Acronym
(HEM-FLU)
Status last verified
Mar 2026
First submitted
17 Mar 2026
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: 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.

Publications

  • Hall VG, Smibert OC, Sullivan SG, Lim C, Barr IG, Peck H, Fuge-Larsen P, Demajo J, Klimevski E, Tennakoon S, Saunders NR, Joyce T, Whitechurch A, Khot A, Anderson MA, Trubiano JA, Yong MK, Worth LJ, Spelman T, Slavin MA, Teh BW. Influenza Vaccination Strategies in Patients with Hematologic Cancer. N Engl J Med. 2025 Jan 16;392(3):306-308. doi: 10.1056/NEJMc2406750. No abstract available.

    PubMed 39813653

  • Silva-Moraes V, Reis LR, Ross TM. Comparative analysis of cellular immune responses to four seasonal inactivated influenza vaccines in younger and older adults. J Immunol. 2026 Feb 9;215(2):vkaf286. doi: 10.1093/jimmun/vkaf286.

    PubMed 41166714

  • Hall VG, Nguyen THO, Smibert OC, Allen LF, Sullivan SG, Fox A, Carolan L, Wheatley AK, Kent SJ, Gilbertson B, Lim C, Barr IG, Peck H, Fuge-Larsen P, Klimevski E, Tennakoon S, Saunders NR, Joyce T, Whitechurch A, Khot A, Anderson MA, Trubiano JA, Worth LJ, Yong MK, Slavin MA, Kedzierska K, Teh BW. Influenza-Specific T-Cell Responses to Vaccination Are Independent of Underlying Hematological Malignancy: Analysis of a Randomized Influenza Vaccination Trial. J Infect Dis. 2025 Dec 20;232(6):1319-1329. doi: 10.1093/infdis/jiaf297.

    PubMed 40600710

  • Kinoshita H, Walti CS, Webber K, Pezzella G, Jensen-Wachspress M, Lang H, Shuey K, Boonyaratanakornkit J, Pergam SA, Chu HY, Bollard CM, Keller MD, Hill JA. T Cell Immune Response to Influenza Vaccination When Administered Prior to and Following Autologous Chimeric Antigen Receptor-Modified T Cell Therapy. Transplant Cell Ther. 2025 May;31(5):327-338. doi: 10.1016/j.jtct.2025.02.019. Epub 2025 Mar 1.

    PubMed 40032074

  • Branagan AR, Duffy E, Gan G, Li F, Foster C, Verma R, Zhang L, Parker TL, Seropian S, Cooper DL, Brandt D, Kortmansky J, Witt D, Ferencz TM, Dhodapkar KM, Dhodapkar MV. Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias. Blood Adv. 2021 Mar 9;5(5):1535-1539. doi: 10.1182/bloodadvances.2020003880.

    PubMed 33683337

  • Natori Y, Humar A, Lipton J, Kim DD, Ashton P, Hoschler K, Kumar D. A pilot randomized trial of adjuvanted influenza vaccine in adult allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2017 Jul;52(7):1016-1021. doi: 10.1038/bmt.2017.24. Epub 2017 Mar 6.

    PubMed 28263288

  • Halasa NB, Savani BN, Asokan I, Kassim A, Simons R, Summers C, Bourgeois J, Clifton C, Vaughan LA, Lucid C, Wang L, Fonnesbeck C, Jagasia M. Randomized Double-Blind Study of the Safety and Immunogenicity of Standard-Dose Trivalent Inactivated Influenza Vaccine versus High-Dose Trivalent Inactivated Influenza Vaccine in Adult Hematopoietic Stem Cell Transplantation Patients. Biol Blood Marrow Transplant. 2016 Mar;22(3):528-35. doi: 10.1016/j.bbmt.2015.12.003. Epub 2015 Dec 17.

    PubMed 26705931

  • Thomas LD, Batarseh E, Hamdan L, Haddadin Z, Dulek D, Kalams S, Stewart LS, Stahl AL, Rahman H, Amarin JZ, Hayek H, Ison M, Overton ET, Pergam SA, Spieker AJ, Halasa NB; Adult HCT Flu Study. Comparison of Two High-Dose Versus Two Standard-Dose Influenza Vaccines in Adult Allogeneic Hematopoietic Cell Transplant Recipients. Clin Infect Dis. 2023 Dec 15;77(12):1723-1732. doi: 10.1093/cid/ciad458.

    PubMed 39219510

  • Whitaker JA, Parikh SA, Shanafelt TD, Kay NE, Kennedy RB, Grill DE, Goergen KM, Call TG, Kendarian SS, Ding W, Poland GA. The humoral immune response to high-dose influenza vaccine in persons with monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL). Vaccine. 2021 Feb 12;39(7):1122-1130. doi: 10.1016/j.vaccine.2021.01.001. Epub 2021 Jan 16.

    PubMed 33461835

  • Teh BW, Leung VKY, Mordant FL, Sullivan SG, Joyce T, Harrison SJ, Khvorov A, Barr IG, Subbarao K, Slavin MA, Worth LJ. A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2021 Dec 6;73(11):e4269-e4277. doi: 10.1093/cid/ciaa1711.

    PubMed 33175132

  • Cowling BJ, Perera RAPM, Valkenburg SA, Leung NHL, Iuliano AD, Tam YH, Wong JHF, Fang VJ, Li APY, So HC, Ip DKM, Azziz-Baumgartner E, Fry AM, Levine MZ, Gangappa S, Sambhara S, Barr IG, Skowronski DM, Peiris JSM, Thompson MG. Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. Clin Infect Dis. 2020 Oct 23;71(7):1704-1714. doi: 10.1093/cid/ciz1034.

    PubMed 31828291

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing High-dose trivalent inactivated influenza vaccine (HD-IIV3), MF59-adjuvanted quadrivalent inactivated influenza vaccine (aIIV4) and Standard-dose trivalent inactivated influenza vaccine (SD-IIV3) in people with Hematologic Neoplasms and Influenza, run by Asan Medical Center at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact So Yun Lim, MD, PhD (+82-10-4120-3816, soyun_lim@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Seroconversion rate at Day 28 post-vaccination (time frame: Day 28 (±7 days) post-vaccination). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07485855, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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