Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 1×106/kg to 1×108/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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental: 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 |
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.
|
Outcome Measures
Primary Outcome Measures
- Adverse events [1 year after EBV-TCR-T treatment]
Percentage of participants with adverse events
Secondary Outcome Measures
- Dose-limiting toxicity (DLT) [28 days after EBV-TCR-T treatment]
Toxic effects considered by the investigators to be related to the EBV-TCR-T
- Maximum tolerated dose （MTD） [28 days after EBV-TCR-T treatment]
The highest dose of DLT was seen in 1/6 of 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
- 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.
- Maximum Plasma Concentration (Cmax) of EBV-TCR-T cells [28 days after EBV-TCR-T treatment]
Cmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
- Area under the plasma concentration versus time curve (AUC) of EBV-TCR-T cells [28 days after EBV-TCR-T treatment]
AUC of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
- Time to peak (Tmax) of EBV-TCR-T cells [28 days after EBV-TCR-T treatment]
Tmax of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
- Half life time (T1/2) of EBV-TCR-T cells [28 days after EBV-TCR-T treatment]
T1/2 of EBV-TCR-T cells in patients with EBV-HLH or EBV infection
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 1-60 years, gender unlimited.
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Diagnosed with EBV associated-hemophagocytic lymphohistiocytosis (HLH) or EBV infection.
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Fully understood and informed the study and signed the ICF.
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Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
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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;
- 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:
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Patients with uncontrolled active aGVHD one day before TCR-T cell infusion.
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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.
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Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
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Use of immunosuppressive drugs or G-CSF within 2 weeks before PBMC blood collection.
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Have tumours, active and uncontrolled malignant diseases.
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Serologically positive for HIV-Ab or TAP-ab.
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Pregnant or lactating women.
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Men and their partners or women of childbearing potential refused contraception during the study period.
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Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
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Participated in any other clinical study of drugs and medical devices before 4 weeks of enrollment.
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Allergy to albumin.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chinese PLA General Hospital | Beijing | Beijing | China | 100853 |
Sponsors and Collaborators
- Chinese PLA General Hospital
Investigators
- Principal Investigator: Daihong Liu, Doctor, Chinese PLA General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- S2022-381-01