Clinical Study of EBV-TCR-T Cells for EBV Infection After Allogenic HSCT
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 virus infection after allogenic HSCT.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 3×105/kg to 1×106/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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EBV-TCR-T cells Phase 1 trail: 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. Phase 2 trail: According to the PK and response data, the dose escalation phase will be carried out. |
Biological: EBV-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.
|
Outcome Measures
Primary Outcome Measures
- Adverse events [1 year after EBV-TCR-T treatment]
Percentage of participants with adverse events.
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 14-75 years, gender unlimited.
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Diagnosed with hematologic malignancies and have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with EBV infection after allo-HSCT.
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Karnofsky Score ≥ 70(age ≥16y) or Lansky Score ≥ 50(age<16y).
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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:
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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) 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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Have other malignancies.
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Have relapsed and uncontrolled hematologic malignancies.
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Serologically positive for HIV-Ab or TAP-ab.
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Pregnant or lactating women.
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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 30 days of enrollment.
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.- S2022-083-01