Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT

Peking University

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Stem Cell Transplant; CMV Infection; EBV Infection

Treatments: Biological: Virus specific T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT06075927

2023PHD006-001

Details and patient eligibility

About

To evaluate the safety and tolerability of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV).

Preliminary evaluation of the efficacy of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV); To monitor the duration and expansion of multi-virus VSTs cells after infusion.

Full description

This study consists of two parts: (1) The first stage is the safety evaluation of multi-virus VSTs and the exploration of DLT and MTD; (2) The second phase is to evaluate the safety and efficacy of multi-viral VSTs in selecting appropriate doses in the first phase.

Enrollment: 29 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age ≥18 years old, and less than or equal to 70 years old, gender is not limited.
• Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplantation.
• Persistent infection with CMV and/or EBV persists despite standard treatment .
• Prednisone or its equivalent hormone is less than or equal to 0.5 mg/kg/ day when enrolled.
• ECOG score ≤3, expected survival greater than 3 months.
• End blood oxygen saturation ≥90% on room air.
• Available multi-virus-specific cytotoxic T lymphocytes.
• Negative pregnancy test in female patients if applicable.
• Written informed consent and/or signed assent line from patient, parent or guardian.

Exclusion criteria

• Within 28 days after allogeneic hematopoietic stem cell transplantation.
• Active III-IV acute GVHD, and/or moderate and above chronic GVHD.
• Severe organ dysfunction: Heart: New York Heart Association (NYHA) levels III and IV; Liver: Total bilirubin>34umol/l; ALT, AST>2 times the normal upper limit; Kidney: Blood creatinine >130umol/L; Lung: Type I or II respiratory failure; Brain: unconsciousness, intracranial hypertension.
• Received DLI, other CTL, CAR-T, NK and other cell therapies, T cell monoclonal antibody immunosuppressants, or participated in any other clinical research related to drugs and medical devices within 28 days before enrollment.
• Poor compliance, and subjects deemed unsuitable for study participation by the investigator.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

VSTs infusion

Experimental group

Description:

Phase I (dose escalation) : An open, single-arm, dose-escalation clinical study to explore the safety, tolerability, and cytodynamic characteristics of CMV and EBV-specific T cells (VSTs), with initial efficacy observations. Subjects enrolled with refractory CMV and/or EBV infection after allogeneic hematopoietic stem cell transplantation were subjected to a 3+3 dose-climb test. Exploring the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of intravenous infusion of multi-virus VSTs. (2) Phase II (dose expansion) : According to the clinically recommended or safe and effective dose determined by the phase I climb test, the extended study of 1-2 dose groups with 20 cases per dose was performed after joint review by the investigators and project collaborators.

Treatment:

Biological: Virus specific T cells