Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT
- Conditions
- EBV Infection After Allogenic HSCT
- Interventions
- Biological: EBV-TCR-T cells
- Registration Number
- NCT06119256
- 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 virus infection after allogenic HSCT.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 12
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description EBV-TCR-T cells EBV-TCR-T cells 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.
- 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 Maximum tolerated dose 28 days after EBV-TCR-T treatment The highest dose of DLT was seen in 1/6 of the 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
The overall response rate to EBV-TCR-T treatment 28,90,180,365,730 days after EBV-TCR-T treatment The overall response rate to EBV-TCR-T treatment
The incidence of EBV reactivation after EBV-TCR-T treatment 1 year after EBV-TCR-T treatment The incidence of EBV reactivation after EBV-TCR-T treatment
Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells 28 days after EBV-TCR-T treatment Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation
Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells 28 days after EBV-TCR-T treatment Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation
Half life time (T1/2) of EBV-TCR-T cells 28 days after EBV-TCR-T treatment Pharmacokinetic (PK) parameters of EBV-TCR-T cells in patients with EBV reactivation
Concentration levels of cytokines 28 days after EBV-TCR-T treatment Concentration levels of cytokines (IL-2, IL-6, IL-10, TNF-α, IFN-γ)
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
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.
Dose-limiting toxicity 28 days after EBV-TCR-T treatment Toxic effects considered by the investigators to be related to the EBV-TCR-T
The incidence of EBV-PTLD 1 year after EBV-TCR-T treatment The incidence of EBV-PTLD after EBV-TCR-T treatment
Persistence of EBV-TCR-T cells 1 year after EBV-TCR-T treatment 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.
The duration of response 1 year after EBV-TCR-T treatment The time from the patients firstly achieve complete remission or partial remission to progression of disease
The complete response rate to EBV-TCR-T treatment 28,90,180,365, and 730 days after EBV-TCR-T treatment The complete response rate to EBV-TCR-T treatment
Concentration levels of CRP 28 days after EBV-TCR-T treatment Pharmacokinetics of EBV-TCR-T cells
The time to response 180 days after EBV-TCR-T treatment The time from the start of therapy to the time when patients firstly achieve complete remission or partial remission
Concentration levels of ferritin 28 days after EBV-TCR-T treatment Pharmacokinetics of EBV-TCR-T cells
Trial Locations
- Locations (1)
Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China