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

Stem Cell Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06075927
• Other study ID #: 2023PHD006-001
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: November 1, 2023
• Est. completion date: October 30, 2025

Study information

• Verified date: October 2023
• Source: Peking University People's Hospital
• Contact: Yuanjie Ding
• Phone: 010-88325948
• Email: rmkyc[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 29
• Est. completion date: October 30, 2025
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• CMV Infection
• Communicable Diseases
• Cytomegalovirus Infections
• EBV Infection
• Epstein-Barr Virus Infections
• Infections
• Stem Cell Transplant

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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