EBV-TCR-T Cells for EB Virus Infection After HSCT

Phase 1

Completed

• Conditions: EBV Emia and EBV Positive PTLD After Allogenic HSCT
• Interventions: Biological: EBV-TCR-T cells

• Registration Number: NCT04156217
• Lead Sponsor: Hebei Yanda Ludaopei Hospital

Brief Summary

This is a single center, single arm, open-label, phase I study to evaluate the safety and efficacy of EBV-TCR-T cells in patients with EB virus infection after HSCT.

Detailed Description

EBV infection is a common virus infection of HSCT, and which is highly related with the failure of transplantation and survival time of transplant patients. To evaluate the safety and efficacy of allogenic EBV-TCR-T cell therapy in subjects with EBV infection, patients with EBV emias or EBV positive PTLD will be enrolled, and donor derived EBV-TCR-T(HLA-A\*1101\\0201\\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 EBV-TCR-T cells. The EBV DNA copies and EBV-TCR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14, day 28).

Study Timeline

• Study First Submitted: 2019-11-04
• Study First Submitted QC: 2019-11-05
• Study First Posted: 2019-11-07
• Study Start: 2020-02-10
• Primary Completion: 2021-07-30
• Status Verified: 2021-08
• Study Completion: 2021-10-31
• Last Update Submitted: 2022-03-06
• Last Update Posted: 2022-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Age 1-70 years, including boundary values, gender unlimited;
2. The EBV DNA copies number of allogenic HSCT patients with EBV infection (EBV emia and EBV positive PTLD) still did not decrease，after treated with lower dosage of Immunosuppressants，or antiviral therapy or Rituximab（Rituxan）；
3. Allogenic HSCT patients could not tolerate the antiviral therapy and / or Rituximab（Rituxan）；
4. The EBV-positive diagnosis criteria: EBV DNA copy number>1000 copies/ ml, or the tissue EBV-EBER pathological result is positive, the diagnosis of PTLD was based on the diagnostic criteria of WHO 2016；
5. Estimated life expectancy ≥ 3 months；
6. ECOG 3 ；
7. Patients who voluntarily sign informed consent and are willing to comply with treatment plans, visit arrangements, laboratory tests and other research procedures.

Exclusion Criteria

1. Patients with active aGVHD III-IV and / or mild and severe cGVHD;

2. Received cell therapy such as DLI,CTL,CAR-T or participated in any other clinical study of drugs and medical devices before 30 days of enrollment；

3. Pregnant or lactating women;

4. Intracranial hypertension or confusion; respiratory failure; disseminated intravascular coagulation;

5. patients with organ failure:

   • Heart: NYHA heart function grade IV;
   • Liver: Grade C that achieves Child-Turcotte liver function grading;
   • Kidney: kidney failure and uremia;
   • Lung: symptoms of respiratory failure;
   • Brain: a person with a disability;

6. The researchers found that it was unsuitable for the recipients to be enrolled.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EBV-TCR-T cells	EBV-TCR-T cells	Patients with EBV emias or EBV positive PTLD will be enrolled, and donor derived EBV-TCR-T(HLA-A\*1101\\0201\\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 EBV-TCR-T cells. The EBV DNA copies and EBV-TCR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14, day 28).

Primary Outcome Measures

Name	Time	Method
Percentage of adverse events	3months	Percentage of participants with adverse events.

Secondary Outcome Measures

Name	Time	Method
changes of EBV-DNA copies	3months
Proliferation ratio of TCR-T cells	3months

Trial Locations

Locations (1)

Hebei Yanda Ludaopei Hospital; 🇨🇳 Sanhe, Hebei, China