Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT

Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT

This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV virus infection after allogenic HSCT.

Study Overview

• Status: Recruiting
• Conditions: EBV Infection After Allogenic HSCT
• Intervention / Treatment: Biological: EBV-TCR-T cells

Detailed Description

EB virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (HSCT) is common and can be lethal without prompt treatment. In this prospective study, HLA-A*02:01/11:01/24:02-restricted EBV-specific T cell receptor (TCR) will be introduced into the T cells of HSCT donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 3×10^5/kg to 1×10^6/kg of EBV-TCR-T cells will be infused into patients with EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daihong Liu, Doctor; Phone Number: +86 18301339032; Email: daihongrm@163.com
• Study Contact Backup: Name: Liping Dou, Doctor; Phone Number: +86 13681207138

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Daihong Liu, doctor; Phone Number: 86-13681171597; Email: daihongrm@163.com
      • Contact: Liping Dou, doctor; Phone Number: 86-13681207138; Email: lipingruirui@163.com
      • Principal Investigator: Daihong Liu, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 14-75 years, gender unlimited.
• Diagnosed with hematologic malignancies and have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with EBV infection after allo-HSCT.
• Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
• TCR-T cell donor inclusion criteria: 1) Age 8-70 years; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.

Exclusion Criteria:

• Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
• Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV) one week before TCR-T cell infusion.
• Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
• Have other malignancies.
• Have relapsed and uncontrolled hematologic malignancies.
• Serologically positive for HIV-Ab or TAP-ab.
• Pregnant or lactating women.
• Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
• Participated in any other clinical study of drugs and medical devices before 30 days of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EBV-TCR-T cells; Phase 1 trail: The patients with EBV infection after HSCT will receive one to three infusions of donor-derived EBV-TCR-T cells, with the escalated dose ranging from 5×10^5/kg to 1×10^6/kg EBV-TCR-T cells per dose. Phase 2 trail: According to the PK and response data, the dose escalation phase will be carried out.	Biological: EBV-TCR-T cells; The patients with EBV infection after HSCT will receive one to three infusions of donor-derived EBV-TCR-T cells, with the escalated dose ranging from 5×10^5/kg to 1×10^6/kg EBV-TCR-T cells per dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Percentage of participants with adverse events.	1 year after EBV-TCR-T treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of EBV-DNA copies number	Quantitative PCR will be used to determine viral copy numbers in peripheral blood.	1 year after EBV-TCR-T treatment
Persistence of EBV-TCR-T cells	Quantitative PCR using primers specific for the gene encoding EBV-TCR will be used to determine the number of circulating EBV-TCR-T cells in peripheral blood post infusion.	1 year after EBV-TCR-T treatment
Dose-limiting toxicity	Toxic effects considered by the investigators to be related to the EBV-TCR-T	28 days after EBV-TCR-T treatment
Maximum tolerated dose	The highest dose of DLT was seen in 1/6 of the subjects	28 days after EBV-TCR-T treatment
The proportion of EBV-DNA negative patients	The proportion of patients EBV-DNA negative after EBV-TCR-T treatment	180 days after EBV-TCR-T treatment
The time to EBV-DNA negative	The time from the start of therapy to EBV-DNA negative detected	180 days after EBV-TCR-T treatment
The time to response	The time from the start of therapy to the time when patients firstly achieve complete remission or partial remission	180 days after EBV-TCR-T treatment
The duration of response	The time from the patients firstly achieve complete remission or partial remission to progression of disease	1 year after EBV-TCR-T treatment
The incidence of EBV-PTLD	The incidence of EBV-PTLD after EBV-TCR-T treatment	1 year after EBV-TCR-T treatment
The overall response rate to EBV-TCR-T treatment	The overall response rate to EBV-TCR-T treatment	28,90,180,365,730 days after EBV-TCR-T treatment
The complete response rate to EBV-TCR-T treatment	The complete response rate to EBV-TCR-T treatment	28,90,180,365, and 730 days after EBV-TCR-T treatment
The incidence of EBV reactivation after EBV-TCR-T treatment	The incidence of EBV reactivation after EBV-TCR-T treatment	1 year after EBV-TCR-T treatment
Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells	Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation	28 days after EBV-TCR-T treatment
Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells	Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation	28 days after EBV-TCR-T treatment
Half life time (T1/2) of EBV-TCR-T cells	Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation	28 days after EBV-TCR-T treatment
Concentration levels of cytokines	Concentration levels of cytokines (IL-2, IL-6, IL-10, TNF-α, IFN-γ)	28 days after EBV-TCR-T treatment
Concentration levels of CRP	Pharmacokinetics of EBV-TCR-T cells	28 days after EBV-TCR-T treatment
Concentration levels of ferritin	Pharmacokinetics of EBV-TCR-T cells	28 days after EBV-TCR-T treatment

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Daihong Liu, Doctor, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: October 21, 2023
• First Submitted That Met QC Criteria: November 3, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: EBV infection; allogenic HSCT
• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Epstein-Barr Virus Infections
• Other Study ID Numbers: S2022-083-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No