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

NCT06075927 | Unknown Phase 1

• 1 other identifier: 2023PHD006-001
• Study Type: interventional
• Target: 29
• Locations: 0 countries
• Sites: N/A

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.

Conditions

CMV Infection; EBV Infection; Stem Cell Transplant

Keywords

Cytomegalovirus; Epstein Barr virus; Multivirus-specific Cytotoxic T-Lymphocytes; Stem Cell Transplant

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Virus-specific immune reconstitution

  within 56 days after the first VSTs infusion

Study Arms (1)

VSTs infusion

EXPERIMENTAL

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

Interventions

Virus specific T cells 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

VSTs infusion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead

MeSH Terms

Conditions

Cytomegalovirus Infections; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Xiangyu Zhao

  Peking University People's Hospital

  STUDY CHAIR

Central Study Contacts

Yuanjie Ding

CONTACT

010-88325948; rmkyc@163.com

Xuying Pei

CONTACT

86-13521893860; peixuying08@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 10, 2023
• Study Start: November 1, 2023
• Primary Completion: July 30, 2025
• Study Completion: October 30, 2025
• Last Updated: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share