Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection

Phase 1

Recruiting

• Conditions: EBV-associated Hemophagocytic Lymphohistiocytosis; EBV Infection
• Interventions: Biological: EBV-TCR-T cells

• Registration Number: NCT06135922
• Lead Sponsor: Chinese PLA General Hospital

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-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection

Detailed Description

Epstein-Barr virus (EBV) is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and asymptomatic EBV shedders. The inability to control EBV infection can lead to some patients developing EBV-positive B-cell lymphomas, chronic active EBV infections, and hemophagocytic lymphohistiocytosis (HLH). 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 donors by ex vivo lentiviral transduction to generate EBV-TCR-T cells. An escalated dose ranging from 1×10\^6/kg to 1×10\^8/kg of EBV-TCR-T cells will be infused into patients with EBV-HLH or EBV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic EBV-TCR-T cell therapy will be evaluated.

Study Timeline

• Study Start: 2023-08-01
• Status Verified: 2023-10
• Study First Submitted: 2023-11-12
• Study First Submitted QC: 2023-11-12
• Last Update Submitted: 2023-11-12
• Study First Posted: 2023-11-18
• Last Update Posted: 2023-11-18
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• Age 1-60 years, gender unlimited.
• Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
• Fully understood and informed the study and signed the ICF.
• Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
• TCRT-T cell donor inclusion criteria: 1)Age >=8 years, gender unlimited; 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 or left ventricular ejection fraction<50%) one week before TCR-T cell infusion.
• Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
• Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
• Have tumours, active and uncontrolled malignant diseases.
• Serologically positive for HIV-Ab or TAP-ab.
• Pregnant or lactating women.
• Men and their partners or women of childbearing potential refused contraception during the study period.
• 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 4 weeks of enrollment.
• Allergy to albumin.
• TCRT-T cell donor exclusion criteria: 1) pregnant woman; 2) Serologically positive for HBsAg, HCV-Ab, HIV-Ab or TAP-ab; 3) EBV-DNA or CMV-DNA positive; 4) other uncontrolled infection; 5) Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: EBV-TCR-T cells	EBV-TCR-T cells	The patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10\^6/kg to 1×10\^8/kg EBV-TCR-T cells per dose

Primary Outcome Measures

Name	Time	Method
Adverse events	1 year after EBV-TCR-T treatment	Percentage of participants with adverse events

Secondary Outcome Measures

Name	Time	Method
The proportion of EBV-DNA negative patients	180 days after EBV-TCR-T treatment	The proportion of patients EBV-DNA negative after EBV-TCR-T treatment
Dose-limiting toxicity (DLT)	28 days after EBV-TCR-T treatment	Toxic effects considered by the investigators to be related to the EBV-TCR-T
Maximum tolerated dose （MTD）	28 days after EBV-TCR-T treatment	The highest dose of DLT was seen in 1/6 of subjects
The time to EBV-DNA negative	180 days after EBV-TCR-T treatment	The time from the start of therapy to EBV-DNA negative detected
Changes of EBV-DNA copies number	1 year after EBV-TCR-T treatment	Quantitative PCR will be used to determine viral copy numbers in peripheral blood.
Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells	28 days after EBV-TCR-T treatment	Cmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells	28 days after EBV-TCR-T treatment	AUC of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Time to peak (Tmax) of EBV-TCR-T cells	28 days after EBV-TCR-T treatment	Tmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Half life time (T1/2) of EBV-TCR-T cells	28 days after EBV-TCR-T treatment	T1/2 of EBV-TCR-T cells in patients with EBV-HLH or EBV infection

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China