Evaluation of Safety and Efficacy of Virus Specific T-Cell Administration in Pediatric Patients With Systemic Viral Infection Following Allogeneic Hematopoietic Stem Cell Transplantation.

A Prospective Clinical Study to Evaluate the Safety and Efficacy of Virus Specific T-Cell Administration in Pediatric Patients With Systemic Viral Infection Following Allogeneic Hematopoietic Stem Cell Transplantation.

The goal of this prospective clinical study is to evaluate the safety and efficacy of Multi-Virus Specific T cells (LB-DTK-MV) in pediatric patients with systemic viral infection, including CMV, EBV, and BKV, after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The main questions it aims to answer are:

• What is the maximum tolerated dose of LB-DTK-MV based on dose-limiting toxicity?
• What treatment emergent adverse events occur within 14 days after the second infusion?
• Is there a clinically significant reduction in CMV, EBV, and BKV viral loads within 14 days following the second infusion?
• Is there a clinically significant improvement in clinical symptoms within 14 days following the second infusion?

Participants will:

• Receive a single intravenous infusion of LB-DTK-MV during the baseline visit (low dose: 1x10^7/m^2; high dose: 2x10^7/m^2).
• Receive the second infusion of LB-DTK-MV intravenously at the same dose 14 days after the first infusion.
• Attend weekly follow-up visits at the clinic for 6 months after the first infusion.

Inclusion Criteria:

1. Patients with CMV, EBV, and/or BKV infection that is resistant or refractory to standard-of-care treatment and associated with severe complications following allogeneic hematopoietic stem cell transplantation at the ages of 1-25 years.
2. Patients with evidence of neutrophil engraftment, defined as an absolute neutrophil count (ANC) maintained at 0.5x10^3/μL or higher for 3 consecutive days following allogeneic hematopoietic stem cell transplantation.
3. Patients who have undergone allogeneic hematopoietic stem cell transplantation at least 21 days prior to the screening visit.
4. Patients who show complete donor chimerism (PCR-short tandem repeats ≥ 95%) at the time of first dose administration.
5. Patients who are able to reduce their steroid dosage to 0.5mg/kg/day of Prednisolone (or an equivalent dose) or less.
6. Individuals who have voluntarily decided to participate in this clinical study and have provided written consent to comply with the restrictions.
7. For women of childbearing potential, those who tested negative on a pregnancy test (blood test) performed on the screening visit.
8. Individuals deemed suitable as study subjects through screening tests (vital signs, physical examination, medical and surgical history, electrocardiogram, laboratory tests, etc.).

Exclusion Criteria:

1. 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.

2. Patients with organ failures and/or uncontrolled bacterial or fungal infections.

   • Moderate or severe liver damage [Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN)]
   • Chronic kidney disease [eGFR < 30mL/min/1.73m^2]

3. Patients who have undergone allogeneic hematopoietic stem cell transplantation or received donor lymphocyte infusion (DLI) within 28 days prior to the scheduled first dose.

4. Patients with active graft-versus-host disease (GvHD) of grade 2 or higher.

5. Patients with active malignant tumor or uncontrolled recurrence.

6. Patients deemed ineligible for participation in this clinical study by the investigator.