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

An Exploratory Clinical Study of Multivirus-specific T Cells in the Treatment of Refractory Cytomegalovirus and/or Epstein-Barr Virus Infection After Allogeneic Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stem Cell Transplant; CMV Infection; EBV Infection
• Intervention / Treatment: Biological: Virus specific T cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yuanjie Ding; Phone Number: 010-88325948; Email: rmkyc@163.com
• Study Contact Backup: Name: Xuying Pei; Phone Number: 86-13521893860; Email: peixuying08@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

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: 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.

Biological: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of safety and toxicity outcomes in subjects receiving VSTs infusion	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, and graft-versus-host-disease will be summarized using descriptive statistics for each dose level	within 56 days after the first VSTs infusion
Assessment of antiviral efficacy of VSTs infusion	Antiviral efficacy including clinical signs of viral infections, virus reinfection, and laboratory measurement of viral load after VSTs infusion will be determined	within 56 days after the first VSTs infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virus-specific immune reconstitution	Laboratory measurement of virus-specific immune reconstitution before and after VSTs infusion will be tested	within 56 days after the first VSTs infusion

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Study Chair: Xiangyu Zhao, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: October 4, 2023
• First Posted (Estimated): October 10, 2023

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Cytomegalovirus; Stem Cell Transplant; Epstein Barr virus; Multivirus-specific Cytotoxic T-Lymphocytes
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Epstein-Barr Virus Infections
• Other Study ID Numbers: 2023PHD006-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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