Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: EBV-TCR-T cells.
- Who it may be relevant to
- Registry conditions: EBV-associated Hemophagocytic Lymphohistiocytosis, EBV Infection. Basic parameters: 1 year — 60 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Multicenter, Open Label, Single-arm Exploratory Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
Overview
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.
Interventions
- Biological EBV-TCR-T cells
The patients with EBV-HLH or EBV infection will receive infusions of EBV-TCR-T cells, with the escalated dose ranging from 1×10\^6/kg to 1×10\^8/kg EBV-TCR-T cells per dose.
Primary outcome measures
- Adverse events [Time frame: 1 year after EBV-TCR-T treatment]
Secondary outcome measures (9)
- Dose-limiting toxicity (DLT) [Time frame: 28 days after EBV-TCR-T treatment]
- Maximum tolerated dose （MTD） [Time frame: 28 days after EBV-TCR-T treatment]
- The proportion of EBV-DNA negative patients [Time frame: 180 days after EBV-TCR-T treatment]
- The time to EBV-DNA negative [Time frame: 180 days after EBV-TCR-T treatment]
- Changes of EBV-DNA copies number [Time frame: 1 year after EBV-TCR-T treatment]
- Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells [Time frame: 28 days after EBV-TCR-T treatment]
- Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells [Time frame: 28 days after EBV-TCR-T treatment]
- Time to peak (Tmax) of EBV-TCR-T cells [Time frame: 28 days after EBV-TCR-T treatment]
- Half life time (T1/2) of EBV-TCR-T cells [Time frame: 28 days after EBV-TCR-T treatment]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 1 center
- Chinese PLA General Hospital — Beijing
Identifiers
NCT: NCT06135922 · S2022-381-01