Evaluation of the Safety and Efficacy of LB-DTK-BKV in Patients With BK Virus-Associated Hemorrhagic Cystitis Following Allogeneic Hematopoietic Stem Cell Transplantation

Summary

The goal of this clinical trial is to assess efficacy of BK virus specific T cells (LB-DTK-BKV) to treat pediatric, adolescent, and adult patients with BK virus-associated hemorrhagic cystitis after allogenic hematopoietic stem cell transplantation (allo-HSCT). It will also evaluate the safety of LB-DTK-BKV using treatment-emergent adverse events (TEAEs). The main questions it aims to answer are: * Does LB-DTK-BKV reduce the number of BKV virus viral load in allo-HSCT patients with hemorrhagic cystitis? * Do adverse events occur after the second dose? Researchers will compare LB-DTK-BKV to a placebo to see if LB-DTK-BKV works to treat hemorrhagic cystitis in allo-HSCT patients. Participants will: * Receive a single intravenous infusion of LB-DTK-BKV at the baseline visit (low dose: 1x10\^7/m\^2; high dose: 2x10\^7/m\^2). * Receive the second dose of LB-DTK-BKV intravenously at the same dose 14 days after the first dose. * Visit the clinic every week for follow-up for 6 months after the first dose.

Timeline

Start

2026-09-01

Primary completion

2028-03-01

Completion

2028-03-01

Publications

• Background Jahangiri, V., et al., Post-Transplantation Cyclophosphamide (PTCY) Is Associated with Increased Risk of BK Virus-Associated Hemorrhagic Cystitis (BKHC) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT). Biology of Blood and Marrow Transplantation, 2019.25 (3): p. S359-S360.
• Background Cho SG, Kim N, Sohn HJ, Lee SK, Oh ST, Lee HJ, Cho HI, Yim HW, Jung SE, Park G, Oh JH, Choi BO, Kim SW, Kim SW, Chung NG, Lee JW, Hong YS, Kim TG. Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs. Mol Ther. 2015 Aug;23(8):1401-1409. doi: 10.1038/mt.2015.91. Epub 2015 May 28.
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• Background Cruz CR, Hanley PJ, Liu H, Torrano V, Lin YF, Arce JA, Gottschalk S, Savoldo B, Dotti G, Louis CU, Leen AM, Gee AP, Rooney CM, Brenner MK, Bollard CM, Heslop HE. Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience. Cytotherapy. 2010 Oct;12(6):743-9. doi: 10.3109/14653241003709686.
• Background Green A, Rubinstein JD, Grimley M, Pfeiffer T. Virus-Specific T Cells for the Treatment of Systemic Infections Following Allogeneic Hematopoietic Cell and Solid Organ Transplantation. J Pediatric Infect Dis Soc. 2024 Feb 28;13(Supplement_1):S49-S57. doi: 10.1093/jpids/piad077.
• Background Martits-Chalangari K, Spak CW, Askar M, Killian A, Fisher TL, Atillasoy E, Marshall WL, McNeel D, Miller MD, Mathai SK, Gottlieb RL. ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report. Am J Transplant. 2022 Apr;22(4):1261-1265. doi: 10.1111/ajt.16927. Epub 2021 Dec 27.
• Background Vasileiou S, Hill L, Kuvalekar M, Workineh AG, Watanabe A, Velazquez Y, Lulla S, Mooney K, Lapteva N, Grilley BJ, Heslop HE, Rooney CM, Brenner MK, Eagar TN, Carrum G, Grimes KA, Leen AM, Lulla P. Allogeneic, off-the-shelf, SARS-CoV-2-specific T cells (ALVR109) for the treatment of COVID-19 in high-risk patients. Haematologica. 2023 Jul 1;108(7):1840-1850. doi: 10.3324/haematol.2022.281946.
• Background Dadwal SS, Bansal R, Schuster MW, Yared JA, Myers GD, Matzko M, Adnan S, McNeel D, Ma J, Gilmore SA, Vasileiou S, Leen AM, Hill JA, Young JH. Final outcomes from a phase 2 trial of posoleucel in allogeneic hematopoietic cell transplant recipients. Blood Adv. 2024 Sep 10;8(17):4740-4750. doi: 10.1182/bloodadvances.2023011562.
• Background Dekker L, Sanders E, Lindemans CA, de Koning C, Nierkens S. Naive T Cells in Graft Versus Host Disease and Graft Versus Leukemia: Innocent or Guilty? Front Immunol. 2022 Jun 20;13:893545. doi: 10.3389/fimmu.2022.893545. eCollection 2022.
• Background Jalili A, Hajifathali A, Mohammadian M, Sankanian G, Sayahinouri M, Dehghani Ghorbi M, Roshandel E, Aghdami N. Virus-Specific T Cells: Promising Adoptive T Cell Therapy Against Infectious Diseases Following Hematopoietic Stem Cell Transplantation. Adv Pharm Bull. 2023 Jul;13(3):469-482. doi: 10.34172/apb.2023.046. Epub 2022 Nov 4.
• Background Vasileiou S, Turney AM, Kuvalekar M, Mukhi SS, Watanabe A, Lulla P, Ramos CA, Naik S, Vera JF, Tzannou I, Leen AM. Rapid generation of multivirus-specific T lymphocytes for the prevention and treatment of respiratory viral infections. Haematologica. 2020 Jan;105(1):235-243. doi: 10.3324/haematol.2018.206896. Epub 2019 Apr 19. No abstract available.
• Background Vasileiou S, Kuvalekar M, Velazquez Y, Watanabe A, Leen AM, Gilmore SA. Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. Cytotherapy. 2024 Aug;26(8):869-877. doi: 10.1016/j.jcyt.2024.03.012. Epub 2024 Mar 19.
• Background Tzannou I, Papadopoulou A, Naik S, Leung K, Martinez CA, Ramos CA, Carrum G, Sasa G, Lulla P, Watanabe A, Kuvalekar M, Gee AP, Wu MF, Liu H, Grilley BJ, Krance RA, Gottschalk S, Brenner MK, Rooney CM, Heslop HE, Leen AM, Omer B. Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation. J Clin Oncol. 2017 Nov 1;35(31):3547-3557. doi: 10.1200/JCO.2017.73.0655. Epub 2017 Aug 7.
• Background Pfeiffer T, Tzannou I, Wu M, Ramos C, Sasa G, Martinez C, Lulla P, Krance RA, Scherer L, Ruderfer D, Naik S, Bocchini C, Fraser IP, Patel B, Ward D, Wang T, Heslop HE, Leen AM, Omer B. Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting. Clin Cancer Res. 2023 Jan 17;29(2):324-330. doi: 10.1158/1078-0432.CCR-22-2415.
• Background Imlay H, Xie H, Leisenring WM, Duke ER, Kimball LE, Huang ML, Pergam SA, Hill JA, Jerome KR, Milano F, Nichols WG, Pang PS, Hirsch HH, Limaye AP, Boeckh M. Presentation of BK polyomavirus-associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation. Blood Adv. 2020 Feb 25;4(4):617-628. doi: 10.1182/bloodadvances.2019000802.
• Background Chandraker A, Regmi A, Gohh R, Sharma A, Woodle ES, Ansari MJ, Nair V, Chen LX, Alhamad T, Norman S, Cibrik D, Singh M, Alper A, Jain D, Zaky Z, Knechtle S, Sharfuddin A, Gupta G, Lonze BE, Young JH, Adey D, Faravardeh A, Dadhania DM, Rossi AP, Florescu D, Cardarelli F, Ma J, Gilmore S, Vasileiou S, Jindra PT, Wojciechowski D. Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. J Am Soc Nephrol. 2024 May 1;35(5):618-629. doi: 10.1681/ASN.0000000000000329. Epub 2024 Mar 12.
• Background Zhou X, Zhang S, Fan J, Zhu X, Hu S. Risk factors for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis. Clin Transplant. 2023 Nov;37(11):e15121. doi: 10.1111/ctr.15121. Epub 2023 Sep 7.
• Background Cesaro S, Dalianis T, Hanssen Rinaldo C, Koskenvuo M, Pegoraro A, Einsele H, Cordonnier C, Hirsch HH; ECIL-6 Group. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018 Jan 1;73(1):12-21. doi: 10.1093/jac/dkx324.
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• Background Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, Armand P, Antin JH, Chen J, Devine SM, Fowler DH, Luznik L, Nakamura R, O'Donnell PV, Perales MA, Pingali SR, Porter DL, Riches MR, Ringden OT, Rocha V, Vij R, Weisdorf DJ, Champlin RE, Horowitz MM, Fuchs EJ, Eapen M. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015 Aug 20;126(8):1033-40. doi: 10.1182/blood-2015-04-639831. Epub 2015 Jun 30.
• Background Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M, De Bortoli M, Barat V, Prete A, Fagioli F. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study. Biol Blood Marrow Transplant. 2016 May;22(5):902-9. doi: 10.1016/j.bbmt.2016.02.002. Epub 2016 Feb 6.
• Background van den Brink MR, Velardi E, Perales MA. Immune reconstitution following stem cell transplantation. Hematology Am Soc Hematol Educ Program. 2015;2015:215-9. doi: 10.1182/asheducation-2015.1.215. No abstract available.
• Background Khan MA, Bashir Q, Chaudhry QU, Ahmed P, Satti TM, Mahmood SK. Review of Haploidentical Hematopoietic Cell Transplantation. J Glob Oncol. 2018 Dec;4:1-13. doi: 10.1200/JGO.18.00130.
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Drugs

Indications