Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EBV-TCR-T cells | Experimental | Phase 1 trail: 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. Phase 2 trail: According to the PK and response data, the dose escalation phase will be carried out. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EBV-TCR-T cells | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events | Percentage of participants with adverse events. | 1 year after EBV-TCR-T treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Daihong Liu, Doctor | Contact | +86 18301339032 | daihongrm@163.com | |
| Liping Dou, Doctor | Contact | +86 13681207138 |
| Name | Affiliation | Role |
|---|---|---|
| Daihong Liu, Doctor | Chinese PLA General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
Not provided
| ID | Term |
|---|---|
| D020031 | Epstein-Barr Virus Infections |
| ID | Term |
|---|---|
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 1 year after EBV-TCR-T treatment |
| Dose-limiting toxicity | Toxic effects considered by the investigators to be related to the EBV-TCR-T | 28 days after EBV-TCR-T treatment |
| Maximum tolerated dose | The highest dose of DLT was seen in 1/6 of the subjects | 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 | 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 | 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 | 180 days after EBV-TCR-T treatment |
| The duration of response | The time from the patients firstly achieve complete remission or partial remission to progression of disease | 1 year after EBV-TCR-T treatment |
| The incidence of EBV-PTLD | The incidence of EBV-PTLD after EBV-TCR-T treatment | 1 year after EBV-TCR-T treatment |
| The overall response rate to 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 complete response rate to 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 |
| The incidence of EBV reactivation 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 | Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation | 28 days after EBV-TCR-T treatment |
| Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells | Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation | 28 days after EBV-TCR-T treatment |
| Half life time (T1/2) of EBV-TCR-T cells | Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation | 28 days after EBV-TCR-T treatment |
| Concentration levels of cytokines | Concentration levels of cytokines (IL-2, IL-6, IL-10, TNF-α, IFN-γ) | 28 days after EBV-TCR-T treatment |
| Concentration levels of CRP | Pharmacokinetics of EBV-TCR-T cells | 28 days after EBV-TCR-T treatment |
| Concentration levels of ferritin | Pharmacokinetics of EBV-TCR-T cells | 28 days after EBV-TCR-T treatment |
| D014412 |
| Tumor Virus Infections |