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| ID | Type | Description | Link |
|---|---|---|---|
| RS-2025-25468314 | Other Grant/Funding Number | Ministry of health and welfare, South Korea |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard dose Influenza vaccine | Active Comparator | Standard dose Influenza vaccine |
|
| High dose influenza vaccine | Experimental | High dose influenza vaccine |
|
| MF.59 adjuvant influenza vaccine | Experimental | MF.59 adjuvant influenza vaccine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Day 28 (±7 days) post-vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Other Immunogenicity |
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). |
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Inclusion Criteria:
non-Hodgkin lymphoma, Hodgkin lymphoma, acute leukemia, chronic leukemia, or plasma cell disorders
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| 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 |
| Name | Affiliation | Role |
|---|---|---|
| Sung-Han Kim, MD, PhD | Asan Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center | Recruiting | Seoul | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39813653 | Background | 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. | |
| 41166714 |
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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.
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| 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. |
|
| Day 28 (±7 days), Day 180(±30 days), and Day 365(±30 days) post-vaccination |
| Background |
| 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. |
| 40600710 | Background | 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. |
| 40032074 | Background | 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. |
| 33683337 | Background | 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. |
| 28263288 | Background | 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. |
| 26705931 | Background | 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. |
| 39219510 | Background | 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. |
| 33461835 | Background | 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. |
| 33175132 | Background | 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. |
| 31828291 | Background | 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. |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
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