Overview
This exploratory clinical study focuses on the use of EBV-AST cell infusion for treating EBV-DNA viremia following allogeneic hematopoietic stem cell transplantation (Allo-HSCT). The study aims to determine the maximum tolerated dose (MTD) or optimal biological dose (OBD) of EBV-AST cells and assess their safety, tolerability, and preliminary efficacy in treating EBV-DNA viremia. The study will involve a 3+3 dose escalation design to evaluate three different dosages of EBV-AST cell infusion. The study is expected to provide important insights into the clinical application of cell-based therapies for EBV infections.
Description
This clinical trial, initiated by the First Medical Center of the Chinese People's Liberation Army General Hospital, will recruit patients who have experienced EBV-DNA viremia following Allo-HSCT. Patients eligible for inclusion must exhibit EBV-DNA viremia that requires clinical intervention and should meet the inclusion criteria set for the study.
The research employs a 3+3 dose escalation methodology where three dosage groups are evaluated: 3×10\^5 cells/Kg, 1×10\^6 cells/Kg, and 3×10\^6 cells/Kg. Each patient will receive up to three infusions, one per week. The study will monitor both the safety and the preliminary efficacy of the infusions, including their ability to reduce EBV-DNA levels and the duration of EBV-DNA negativity. The trial will also assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the EBV-AST cell infusion.
Eligibility
Inclusion Criteria:
- The patient must be aged 18-75 years.
- ust have undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT).
- Must have EBV-DNA viremia post-transplant, with EBV-DNA \> 1000 copies/mL (on two consecutive tests or one test \> 10,000 copies/mL).
- Karnofsky Performance Score (KPS) of 70 or higher.
- Expected survival of at least 3 months.
- Sufficient organ function, including renal (serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min), hepatic (AST, ALT, and total bilirubin ≤ 5 × ULN), and hematologic parameters (platelets ≥ 10 × 10\^9/L, neutrophils ≥ 1.0 × 10\^9/L).
- HLA-matching criteria must be met for the donor/recipient.
Exclusion Criteria:
- Active GVHD (Grade 2 or higher) or requiring \>0.5 mg/kg/day corticosteroids for GVHD.
- History of CMV viremia or disease within the past week.
- PTLD (Post-Transplant Lymphoproliferative Disorder) diagnosed or suspected within 1 week before infusion.
- Severe active infections (excluding EBV and CMV).
- Serious allergic reactions or contraindications to the infusion.
- Previous immune therapy-related adverse events of Grade 3 or higher.
- History of HIV, HCV, or HBV infection with an active viral load.
