CMV Infection, EBV Infection, Stem Cell Transplant
Conditions
Keywords
Cytomegalovirus, Epstein Barr virus, Multivirus-specific Cytotoxic T-Lymphocytes, Stem Cell Transplant
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.
Interventions
BIOLOGICALVirus 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
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Contacts
Primary ContactYuanjie Ding
Backup ContactXuying Pei
Outcome results
None listed