Patients After Hematopoietic Stem Cell Transplantation
Conditions
Keywords
HSCT
Brief summary
The purpose of this clinical trial is to investigate the efficacy of the EBV mRNA vaccine (WGc-0401 injection) in preventing EBV-related diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to evaluate the safety and efficacy of this vaccine in patients following allo-HSCT. The main study questions are: 1. The incidence of grade III-IV acute graft-versus-host disease (aGVHD) within 100 days, and the occurrence of ≥ grade 3 adverse events (AEs) that are possibly or definitely related to the vaccine, in patients receiving EBV mRNA vaccination after allo-HSCT. 2. To determine the optimal biological dose (OBD) of the EBV mRNA vaccine in patients after allo-HSCT among the dose levels of 25μg, 50μg, 75μg, or 100μg. 3. EBV-ELISpot levels, the incidence of EBV viremia (EBV DNAemia), the incidence of post-transplant lymphoproliferative disorders (PTLD), disease relapse rate during follow-up, non-relapse mortality (NRM), and immunogenicity indicators (IFN-γ+ T cells, immune cell analysis, cytokine profiles, EBV glycoprotein antigen antibodies). Participants will: 1. Receive three intramuscular injections of the EBV mRNA vaccine on days 30, 44, and 81 after allogeneic hematopoietic stem cell transplantation (d30, d44, d81). 2. Be hospitalized for at least 72 hours after each vaccination for close monitoring (with a focus on CRS and aGVHD), and undergo intensive safety assessments throughout the dose-escalation period (at least 28 days). 3. Return for clinical visits on days 7 (d37, d51, d88), day 14 (d58), and day 180 (d180) after vaccination for EBV-ELISpot, EBV-DNA quantification, and immunogenicity testing, with continued long-term follow-up to evaluate safety and the persistence of vaccine-induced immune responses.
Interventions
BIOLOGICALIntramuscular injection of EBV mRNA vaccine (WGc-0401 injection)
Intramuscular injection of EBV mRNA vaccine (WGc-0401 injection)
Sponsors
The General Hospital of Western Theater Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥14 years, regardless of gender; * Patients undergoing allogeneic hematopoietic stem cell transplantation; * Voluntary participation in the clinical study and signing of the informed consent form.
Exclusion criteria
* History of vaccine allergy; * Presence of active acute graft-versus-host disease (aGVHD) at screening; * Severe impairment of cardiac, hepatic, or renal function; * Body temperature \>38°C within 72 hours prior to enrollment; * Inability to communicate reliably with the investigator or unlikely to comply with study requirements; * Any other condition deemed by the investigator to make the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of grade III-IV acute graft-versus-host disease (aGVHD) | Up to 100 days after HSCT | Assessed according to the modified Glucksberg criteria (or the MAGIC criteria), with clinical staging comprehensively determined by the attending physician based on the involvement of skin, upper and lower gastrointestinal tract, and liver. |
| Incidence of grade ≥3 treatment related adverse events (TRAEs) | Up to 180 days after HSCT | AEs graded per CTCAE v6.0. Grade ≥3 AEs with causality assessed as possibly, probably, or definitely related to the vaccine are captured. Systematic AE assessment at each visit covers: local injection site reactions, systemic symptoms (fever, fatigue), laboratory abnormalities (cytopenias, transaminitis), and hypersensitivity. Causality determined by investigator based on temporal association, biological plausibility, and exclusion of other causes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of EBV viremia | From Day 30 to Day 180 post-transplant | EBV-DNA load measured in plasma by quantitative real-time PCR (qPCR). Abnormal viremia defined as either: (1) ≥10³ copies/mL on two consecutive measurements (with an interval of at least 1 day), or (2) a single measurement ≥10⁴ copies/mL. |
| EBV-specific T-cell response measured by IFN-γ ELISpot | Post-transplant days 37, 44, 51, 58, 81, 88, and 180 | EBV-specific T-cell immune response measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay using peripheral blood mononuclear cells (PBMCs) stimulated with EBV peptide pools (e.g., LMP2, EBNA1, BZLF1). Results expressed as spot-forming cells (SFC) per 2×10⁵ PBMCs. Positive response defined as ≥25 SFC/2×10⁵ PBMCs and at least 2-fold above negative control. Samples collected at protocol-specified time points. |
| Incidence of post-transplant lymphoproliferative disorders (PTLD) | From HSCT (day 0) through 12 months post-transplant | PTLD confirmed by tissue biopsy per WHO classification. EBV status by EBER in situ hybridization. Subtypes: early lesions, polymorphic, monomorphic, or classic Hodgkin lymphoma-type. Clinical presentation, sites, and response recorded. |
| Underlying disease relapse rate | Day 0 to 12 months post-HSCT | Relapse defined as recurrence of primary disease post-HSCT. Confirmed by bone marrow (≥5% blasts), flow cytometry, cytogenetics/FISH, molecular markers, or extramedullary biopsy/imaging as indicated. |
| EBV vaccine-induced humoral and cellular immune responses | Pre-vaccination (baseline) and 24h post-vaccination (antibodies/T-cells); pre-vaccination and 6h, 24h post-vaccination (cytokines). Per vaccination dose. | Immunogenicity indicators: (1) EBV-specific antibodies (VCA-IgG, EBNA1-IgG) by ELISA; (2) EBV-specific T-cell responses by IFN-γ ELISpot; (3) serum cytokines/chemokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) by multiplex assay. All samples processed at central lab. |
| Non-relapse mortality (NRM) | Cumulative NRM at day 100 and 12 months post-HSCT | Death from any cause except relapse/progression post-HSCT. Causes: infection, organ failure, GVHD, second malignancy, hemorrhage, other transplant-related causes. Deaths without documented relapse included as NRM. |
Countries
China
Contacts
CONTACTshan zhang
CONTACThai yi
Outcome results
None listed