EBV-AST Cell Therapy for EBV-Related Diseases After Stem Cell Transplantation

Phase 2RecruitingNCT07438067

Daihong Liu18 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

EBV-DNA Viremia

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. The patient must be aged 18-75 years. 2. ust have undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT). 3. Must have EBV-DNA viremia post-transplant, with EBV-DNA \> 1000 copies/mL (on two consecutive tests or one test \> 10,000 copies/mL). 4. Karnofsky Performance Score (KPS) of 70 or higher. 5. Expected survival of at least 3 months. 6. 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). 7. HLA-matching criteria must be met for the donor/recipient. Exclusion Criteria: 1. Active GVHD (Grade 2 or higher) or requiring \>0.5 mg/kg/day corticosteroids for GVHD. 2. History of CMV viremia or disease within the past week. 3. PTLD (Post-Transplant Lymphoproliferative Disorder) diagnosed or suspected within 1 week before infusion. 4. Severe active infections (excluding EBV and CMV). 5. Serious allergic reactions or contraindications to the infusion. 6. Previous immune therapy-related adverse events of Grade 3 or higher. 7. History of HIV, HCV, or HBV infection with an active viral load.

Outcomes

Primary Outcomes

Maximum Tolerated Dose (MTD) of EBV-AST Cell Infusion

The primary outcome measure of the study is to determine the maximum tolerated dose (MTD) of EBV-AST cell infusion in patients with EBV-DNA viremia following allogeneic hematopoietic stem cell transplantation (Allo-HSCT). A dose-escalation design (3×10\^5, 1×10\^6, and 3×10\^6 cells/kg) will be used to evaluate safety and tolerability based on the occurrence of dose-limiting toxicities (DLTs).

Time frame: Day 1 through 28 days after each EBV-AST cell infusion during the dose escalation phase.

Secondary Outcomes

Proportion of Patients Achieving EBV-DNA Negativity

The proportion of patients achieving EBV-DNA negativity following EBV-AST cell infusion.

Time frame: 8 weeks and 12 weeks after EBV-AST cell infusion.

Change in EBV-DNA Levels

Change in EBV-DNA viral load from baseline following EBV-AST cell infusion.

Time frame: Baseline through 12 weeks after EBV-AST cell infusion.

Time to EBV-DNA Negativity

Time from EBV-AST cell infusion to first documented EBV-DNA negativity.

Time frame: Up to 12 weeks after EBV-AST cell infusion.

Absolute Concentration of Circulating EBV-AST Cells in Peripheral Blood at Pre-specified Time Points

Quantification of the absolute number of viable EBV-AST cells per microliter (μL) of peripheral blood using flow cytometry.

Time frame: Baseline through 28 days after EBV-AST cell infusion

Change in EBV-Specific T-Cell Frequency in Peripheral Blood

The fold change in the frequency of circulating EBV-specific T cells (LMP1/2-specific, EBNA1-specific) from baseline, as measured by flow cytometry or ELISpot.