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

NCT ID: NCT06075927

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2025-10-30

Brief Summary

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.

Detailed 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.

Conditions

CMV Infection; EBV Infection; Stem Cell Transplant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VSTs infusion

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.

Group Type: EXPERIMENTAL

Virus specific T cells

Intervention Type: BIOLOGICAL

Subjects will receive partial HLA-matched viral-specific T cells (VSTs) against both CMV and EBV on one of the following dose levels:

Level One: 1 x 10^7 cells/m2 Level Two: 2 x 10^7cells/m2 Level Three: 5x 10^7 cellss/m2

Interventions

Virus specific T cells

Subjects will receive partial HLA-matched viral-specific T cells (VSTs) against both CMV and EBV on one of the following dose levels:

Level One: 1 x 10^7 cells/m2 Level Two: 2 x 10^7cells/m2 Level Three: 5x 10^7 cellss/m2

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiao-Jun Huang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiangyu Zhao

Role: STUDY_CHAIR

Peking University People's Hospital

Central Contacts

Yuanjie Ding

Role: CONTACT

rmkyc@163.com

010-88325948

Xuying Pei

Role: CONTACT

peixuying08@126.com

86-13521893860

Other Identifiers

2023PHD006-001

Identifier Type: -

Identifier Source: org_study_id