EBV Infection After Allogenic HSCT
Conditions
Keywords
EBV infection, allogenic HSCT
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.
Interventions
BIOLOGICALEBV-TCR-T cells
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.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 1 year after EBV-TCR-T treatment | Percentage of participants with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Dose-limiting toxicity | 28 days after EBV-TCR-T treatment | Toxic effects considered by the investigators to be related to the EBV-TCR-T |
| Maximum tolerated dose | 28 days after EBV-TCR-T treatment | The highest dose of DLT was seen in 1/6 of the subjects |
| 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 |
| 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 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 |
| 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 incidence of EBV-PTLD | 1 year after EBV-TCR-T treatment | The incidence of EBV-PTLD after 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 overall 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 complete 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) |
| Concentration levels of CRP | 28 days after EBV-TCR-T treatment | Pharmacokinetics of EBV-TCR-T cells |
| Concentration levels of ferritin | 28 days after EBV-TCR-T treatment | Pharmacokinetics of EBV-TCR-T cells |
Countries
China
Contacts
CONTACTDaihong Liu, Doctor
CONTACTLiping Dou, Doctor
PRINCIPAL_INVESTIGATORDaihong Liu, Doctor
Chinese PLA General Hospital
Outcome results
None listed