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.
Patients who have undergone allogeneic hematopoietic stem cell transplantation, including pediatric and adolescent patients as well as adults who were 12 years of age or older at the time of transplantation. However, only adults aged 19 years or older are eligible for enrollment in Phase 1.
Patients diagnosed with BK virus-associated hemorrhagic cystitis who meet all three of the following criteria.
Clinical symptoms and signs of cystitis, such as lower abdominal pain and dysuria
Hematuria of grade 2 or higher according to the Bedi criteria
Individuals who have received treatment with ATG (Antithymocyte Globulin), Campath (Alemtuzumab), or other T-cell immunosuppressive monoclonal antibodies within 28 days prior to the first dose.
Patients with hemorrhagic cystitis caused by adenovirus (excluded via urine PCR)
Patients with bacterial growth in urine culture (excluded via bacterial culture)
Uncontrolled hypertension
Parallel
LB-DTK-BKV
Biological/VaccineLB-DTK-BKV derived from a designated donor determined based on the type of allogeneic hematopoietic stem cell transplant the subject is undergoing. A pale yellow cell suspension filled in a colorless, transparent freeze-dried vial that is stored frozen until thawed into liquid before administration. Study participants will receive a single intravenous infusion of the assigned cell dose (low dose: 1x10\^7/m\^2;high dose: 2x10\^7/m\^2) on Visit 2 and 14 days after the initial dose.
Standard-of-care
Other interventionStandard-of-care therapy for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation will be administered according to the participant's clinical status by the principal investigator. Participants in the placebo group will not receive LB-DTK-BKV during the clinical trial.
BK virus viral load
BK viral load testing is performed using RT-PCR on urine samples. Viral load is measured weekly for the first 4 weeks, followed by two measurements at 2-week intervals to monitor the progression of the infection, then once every 4 weeks, and subsequently once every 12 weeks. (That is, measurements are taken at weeks 1, 2, 3, 4, 6, 8, 12, and 24 after treatment initiation.)
Immunogenicity Testing
Immunogenicity testing using the IFN-γ ELISpot assay is performed weekly for the first 4 weeks following administration of the investigational drug. Thereafter, to evaluate the persistence and reconstitution of the immune response, measurements are taken twice at 2-week intervals, once at 4-week intervals, and once at 12-week intervals. (i.e., measurements are taken at weeks 1, 2, 3, 4, 6, 8, 12, and 24 after dosing)
Adverse Events
The investigator must confirm the occurrence of adverse events through medical examinations, including interviews and medical history reviews, during regular visits throughout the clinical trial period. Adverse events shall be assessed at each visit starting from the administration of the investigational drug at the baseline visit (Visit 2); however, from the baseline visit (Visit 2) until the discharge date, adverse events shall be assessed daily, and after the discharge date, assessments shall be conducted according to the procedures for each visit; diseases or symptoms that occurred prior to the first administration of the investigational drug shall be collected as part of the medical history.
BK virus viral load
BK viral load testing is performed using RT-PCR on blood samples. Viral load is measured weekly for the first 4 weeks, followed by two measurements at 2-week intervals to monitor the progression of the infection, then once every 4 weeks, and subsequently once every 12 weeks. (That is, measurements are taken at weeks 1, 2, 3, 4, 6, 8, 12, and 24 after treatment initiation.)
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