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

A Pilot Study of EBV-TCR-T Cells in EB Virus Infection Diseases After HSCT

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.

Study Overview

• Status: Completed
• Conditions: EBV Emia and EBV Positive PTLD After Allogenic HSCT
• Intervention / Treatment: Biological: EBV-TCR-T cells

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Hebei Yanda Ludaopei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

Biological: EBV-TCR-T cells; EBV-TCR-T cells are prepared via lentiviral 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of adverse events	Percentage of participants with adverse events.	3months

Secondary Outcome Measures

Outcome Measure	Time Frame
Proliferation ratio of TCR-T cells	3months
changes of EBV-DNA copies	3months

Collaborators and Investigators

• Sponsor: Hebei Yanda Ludaopei Hospital
• Collaborators: China Immunotech (Beijing) Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): October 31, 2021

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 6, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: HXYT-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No