Clinical trial NCT06119256: Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT
Official title: Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: EBV Infection After Allogenic HSCT
Keywords: EBV infection
allogenic HSCT
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2023-11-07
Enrollment: 12
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: 1 year after EBV-TCR-T treatment
Secondary outcomes:
measure: Changes of EBV-DNA copies number
timeFrame: 1 year after EBV-TCR-T treatment
measure: Persistence of EBV-TCR-T cells
timeFrame: 1 year after EBV-TCR-T treatment
measure: Dose-limiting toxicity
timeFrame: 28 days after EBV-TCR-T treatment
measure: Maximum tolerated dose
timeFrame: 28 days after EBV-TCR-T treatment
measure: The proportion of EBV-DNA negative patients
timeFrame: 180 days after EBV-TCR-T treatment
measure: The time to EBV-DNA negative
timeFrame: 180 days after EBV-TCR-T treatment
measure: The time to response
timeFrame: 180 days after EBV-TCR-T treatment
measure: The duration of response
timeFrame: 1 year after EBV-TCR-T treatment
measure: The incidence of EBV-PTLD
timeFrame: 1 year after EBV-TCR-T treatment
measure: The overall response rate to EBV-TCR-T treatment
timeFrame: 28,90,180,365,730 days after EBV-TCR-T treatment
measure: The complete response rate to EBV-TCR-T treatment
timeFrame: 28,90,180,365, and 730 days after EBV-TCR-T treatment
measure: The incidence of EBV reactivation after EBV-TCR-T treatment
timeFrame: 1 year after EBV-TCR-T treatment
measure: Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells
timeFrame: 28 days after EBV-TCR-T treatment
measure: Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells
timeFrame: 28 days after EBV-TCR-T treatment
measure: Half life time (T1/2) of EBV-TCR-T cells
timeFrame: 28 days after EBV-TCR-T treatment
measure: Concentration levels of cytokines
timeFrame: 28 days after EBV-TCR-T treatment
measure: Concentration levels of CRP
timeFrame: 28 days after EBV-TCR-T treatment
measure: Concentration levels of ferritin
timeFrame: 28 days after EBV-TCR-T treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Daihong Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
References: