Clinical trial NCT06135922: Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
Official title: Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: EBV-associated Hemophagocytic Lymphohistiocytosis
EBV Infection
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 9
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
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-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age 1-60 years, gender unlimited.
* Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
* Fully understood and informed the study and signed the ICF.
* Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age\<16y).
* TCRT-T cell donor inclusion criteria: 1)Age \>=8 years, gender unlimited; 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 or left ventricular ejection fraction\<50%) one week before TCR-T cell infusion.
* Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
* Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
* Have tumours, active and uncontrolled malignant diseases.
* Serologically positive for HIV-Ab or TAP-ab.
* Pregnant or lactating women.
* Men and their partners or women of childbearing potential refused contraception during the study period.
* 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 4 weeks of enrollment.
* Allergy to albumin.
* TCRT-T cell donor exclusion criteria: 1) pregnant woman; 2) Serologically positive for HBsAg, HCV-Ab, HIV-Ab or TAP-ab; 3) EBV-DNA or CMV-DNA positive; 4) other uncontrolled infection; 5) Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.

Primary outcomes:
measure: Adverse events
timeFrame: 1 year after EBV-TCR-T treatment
Secondary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 28 days after EBV-TCR-T treatment
measure: Maximum tolerated dose （MTD）
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: Changes of EBV-DNA copies number
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: Time to peak (Tmax) 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
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: