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

EBV Infection Clinical Trial

Official title:

Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06135922
• Other study ID #: S2022-381-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 1, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: October 2023
• Source: Chinese PLA General Hospital
• Contact: Daihong Liu, Doctor
• Phone: +86 18301339032
• Email: daihongrm[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• EBV Infection
• Epstein-Barr Virus Infections
• Infections
• Lymphohistiocytosis, Hemophagocytic

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Percentage of participants with adverse events	1 year after EBV-TCR-T treatment
Secondary	Dose-limiting toxicity (DLT)	Toxic effects considered by the investigators to be related to the EBV-TCR-T	28 days after EBV-TCR-T treatment
Secondary	Maximum tolerated dose (MTD)	The highest dose of DLT was seen in 1/6 of subjects	28 days after EBV-TCR-T treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells	Cmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection	28 days after EBV-TCR-T treatment
Secondary	Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells	AUC of EBV-TCR-T cells in patients with EBV-HLH or EBV infection	28 days after EBV-TCR-T treatment
Secondary	Time to peak (Tmax) of EBV-TCR-T cells	Tmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection	28 days after EBV-TCR-T treatment
Secondary	Half life time (T1/2) of EBV-TCR-T cells	T1/2 of EBV-TCR-T cells in patients with EBV-HLH or EBV infection	28 days after EBV-TCR-T treatment