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

Primary Purpose

CMV Infection, EBV Infection, Stem Cell Transplant

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Virus specific T cells
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CMV Infection focused on measuring Cytomegalovirus, Epstein Barr virus, Multivirus-specific Cytotoxic T-Lymphocytes, Stem Cell Transplant

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    VSTs infusion

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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
    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

    Secondary Outcome Measures

    Virus-specific immune reconstitution
    Laboratory measurement of virus-specific immune reconstitution before and after VSTs infusion will be tested

    Full Information

    First Posted
    September 12, 2023
    Last Updated
    October 4, 2023
    Sponsor
    Peking University People's Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06075927
    Brief Title
    Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 1, 2023 (Anticipated)
    Primary Completion Date
    July 30, 2025 (Anticipated)
    Study Completion Date
    October 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Peking University People's Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    CMV Infection, EBV Infection, Stem Cell Transplant
    Keywords
    Cytomegalovirus, Epstein Barr virus, Multivirus-specific Cytotoxic T-Lymphocytes, Stem Cell Transplant

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    29 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    VSTs infusion
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    Virus specific T cells
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    Assessment of safety and toxicity outcomes in subjects receiving VSTs infusion
    Description
    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
    Time Frame
    within 56 days after the first VSTs infusion
    Title
    Assessment of antiviral efficacy of VSTs infusion
    Description
    Antiviral efficacy including clinical signs of viral infections, virus reinfection, and laboratory measurement of viral load after VSTs infusion will be determined
    Time Frame
    within 56 days after the first VSTs infusion
    Secondary Outcome Measure Information:
    Title
    Virus-specific immune reconstitution
    Description
    Laboratory measurement of virus-specific immune reconstitution before and after VSTs infusion will be tested
    Time Frame
    within 56 days after the first VSTs infusion

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Yuanjie Ding
    Phone
    010-88325948
    Email
    rmkyc@163.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xuying Pei
    Phone
    86-13521893860
    Email
    peixuying08@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Xiangyu Zhao
    Organizational Affiliation
    Peking University People's Hospital
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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

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