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

Chinese PLA General Hospital1 site in 1 country12 target enrollmentAugust 1, 2023

ConditionsEBV Infection After Allogenic HSCT

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: EBV Infection After Allogenic HSCT
Sponsor: Chinese PLA General Hospital
Enrollment: 12
Locations: 1
Primary Endpoint: Adverse events
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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.

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.

Registry

clinicaltrials.gov

Start Date

August 1, 2023

End Date

December 31, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Chinese PLA General Hospital

Responsible Party

Principal Investigator

Daihong Liu

Director

Chinese PLA General Hospital

Eligibility Criteria

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.

Outcomes

Primary Outcomes

Adverse events

Time Frame: 1 year after EBV-TCR-T treatment

Percentage of participants with adverse events.

Secondary Outcomes

The time to EBV-DNA negative(180 days after 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 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(28 days after EBV-TCR-T treatment)
Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells(28 days after EBV-TCR-T treatment)
Half life time (T1/2) of EBV-TCR-T cells(28 days after EBV-TCR-T treatment)
Concentration levels of cytokines(28 days after EBV-TCR-T treatment)
Maximum tolerated dose(28 days after EBV-TCR-T treatment)
The proportion of EBV-DNA negative patients(180 days after EBV-TCR-T treatment)
Changes of EBV-DNA copies number(1 year after EBV-TCR-T treatment)
Dose-limiting toxicity(28 days after EBV-TCR-T treatment)
The incidence of EBV-PTLD(1 year after EBV-TCR-T treatment)
Persistence of EBV-TCR-T cells(1 year after EBV-TCR-T treatment)
The duration of response(1 year after 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)
Concentration levels of CRP(28 days after EBV-TCR-T treatment)
The time to response(180 days after EBV-TCR-T treatment)
Concentration levels of ferritin(28 days after EBV-TCR-T treatment)