Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
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Outcome Measures
Primary Outcome Measures
- Assessment of safety and toxicity outcomes in subjects receiving VSTs infusion [within 56 days after the first 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
- Assessment of antiviral efficacy of VSTs infusion [within 56 days after the first VSTs infusion]
Antiviral efficacy including clinical signs of viral infections, virus reinfection, and laboratory measurement of viral load after VSTs infusion will be determined
Secondary Outcome Measures
- Virus-specific immune reconstitution [within 56 days after the first VSTs infusion]
Laboratory measurement of virus-specific immune reconstitution before and after VSTs infusion will be tested
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years old, and less than or equal to 70 years old, gender is not limited.
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Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplantation.
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Persistent infection with CMV and/or EBV persists despite standard treatment .
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Prednisone or its equivalent hormone is less than or equal to 0.5 mg/kg/ day when enrolled.
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ECOG score ≤3, expected survival greater than 3 months.
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End blood oxygen saturation ≥90% on room air.
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Available multi-virus-specific cytotoxic T lymphocytes.
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Negative pregnancy test in female patients if applicable.
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Written informed consent and/or signed assent line from patient, parent or guardian.
Exclusion Criteria:
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Within 28 days after allogeneic hematopoietic stem cell transplantation.
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Active III-IV acute GVHD, and/or moderate and above chronic GVHD.
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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.
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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.
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Poor compliance, and subjects deemed unsuitable for study participation by the investigator.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Peking University People's Hospital
Investigators
- Study Chair: Xiangyu Zhao, Peking University People's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023PHD006-001