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

Phase 1RecruitingNCT06119256

Chinese PLA General Hospital12 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

EBV Infection After Allogenic HSCT

Interventions

EBV-TCR-T cellsBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 14 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Adverse events

Percentage of participants with adverse events.

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

Secondary Outcomes

Changes of EBV-DNA copies number

Quantitative PCR will be used to determine viral copy numbers in peripheral blood.

Time frame: 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.

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

Dose-limiting toxicity

Toxic effects considered by the investigators to be related to the EBV-TCR-T

Time frame: 28 days after EBV-TCR-T treatment

Maximum tolerated dose

The highest dose of DLT was seen in 1/6 of the subjects

Time frame: 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

Time frame: 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

Time frame: 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

Central Contacts

Daihong Liu, Doctor

CONTACT

+86 18301339032 daihongrm@163.com

Liping Dou, Doctor

CONTACT

+86 13681207138

Data from ClinicalTrials.gov

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