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
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
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.
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGAdverse events
Percentage of participants with adverse events
Time frame: 1 year after EBV-TCR-T treatment
Dose-limiting toxicity (DLT)
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 (MTD)
The highest dose of DLT was seen in 1/6 of 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
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
Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells
Cmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Time frame: 28 days after EBV-TCR-T treatment
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
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Time frame: 28 days after EBV-TCR-T treatment
Time to peak (Tmax) of EBV-TCR-T cells
Tmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Time frame: 28 days after EBV-TCR-T treatment
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
Time frame: 28 days after EBV-TCR-T treatment