Clinical trial NCT06075927: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: CMV Infection
EBV Infection
Stem Cell Transplant
Keywords: Cytomegalovirus
Epstein Barr virus
Multivirus-specific Cytotoxic T-Lymphocytes
Stem Cell Transplant
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2023-10-10
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Assessment of safety and toxicity outcomes in subjects receiving VSTs infusion
timeFrame: within 56 days after the first VSTs infusion
measure: Assessment of antiviral efficacy of VSTs infusion
timeFrame: within 56 days after the first VSTs infusion
Secondary outcomes:
measure: Virus-specific immune reconstitution
timeFrame: within 56 days after the first VSTs infusion
Other outcomes:
Locations:
Study officials:
affiliation: Peking University People's Hospital
name: Xiangyu Zhao
role: STUDY_CHAIR
References: