Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT
CMV Infection, EBV Infection, Stem Cell Transplant
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
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
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.