Epstein-Barr Virus Associated Lymphoma
Conditions
Keywords
relapsed or refractory lymphoma, Epstein-Barr virus mRNA vaccine, Epstein-Barr virus-positive lymphoma
Brief summary
This exploratory study, based on a pharmaceutical company-initiated clinical trial, aims to investigate the therapeutic effects of the EBV mRNA vaccine (WGc-043 injection) in treating EBV-positive relapsed or refractory lymphoma. The study explores the mechanism of the EBV mRNA vaccine (WGc-043 injection) within the tumor microenvironment in EBV-positive lymphoma, elucidating the vaccine's inhibitory effects on EBV. This research will provide a theoretical foundation for the application of mRNA vaccines, either alone or in combination with other immunotherapies, in the treatment of EBV-positive lymphoma.
Interventions
DRUGEBV mRNA vaccine (WGc-043)
Each subject will be infused with EBV mRNA vaccine per administration, including 5 doses for the primary immunization regimen and subsequent optional personalized treatment. For the primary immunization, the first 4 doses will be administered weekly, with the 5th dose given 4 weeks after the 4th dose. The specific dose of mRNA vaccine will be determined according to the experimental group.
Sponsors
Ruijin Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 18 to 75 years (inclusive). 2. Histologically or cytologically diagnosed as relapsed or refractory EBV-positive lymphoma (confirmed by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) showing EBER positivity in tumor tissue) that has failed standard treatment and lacks effective treatment options. This includes, but is not limited to, NK/T-cell lymphoma, Diffuse Large B-cell Lymphoma (DLBCL), or other Peripheral T-cell Lymphomas (PTCL).Relapse is defined as the appearance of new lesions in the primary site or elsewhere after achieving complete remission (CR). (1)Refractory is defined by any of the following conditions: No partial response (PR) after ≥2 cycles of treatment. No CR after ≥4 cycles of treatment. No complete remission (CR) after autologous hematopoietic stem cell transplantation. If the best response or reason for discontinuation is progressive disease (PD), no cycle number requirements apply. (2)Prior treatment must include: 1. Relapsed/Refractory DLBCL: Must have received at least second-line systemic therapy. 2. Relapsed/Refractory Peripheral T-cell Lymphoma: Must have received at least first-line systemic therapy. 3. Relapsed/Refractory NK/T-cell Lymphoma: Must have received a regimen based on L-asparaginase (I/II stage diseases as per the nasal NK/T-cell lymphoma CA staging system must have also received radiotherapy). 3.Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-2 points. 4.Expected survival ≥3 months. 5.At least one measurable lesion as defined by the Lymphoma Classification (2014 version), with measurable lesions defined as: 1. A lymph node lesion with a maximum long diameter \>15 mm on enhanced CT, MRI, or PET-CT. 2. An extranodal lesion with a maximum long diameter \>10 mm. 6.Adequate organ function as evidenced by the following criteria: <!-- --> 1. No use of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human erythropoietin, recombinant human thrombopoietin, or blood component transfusion within 14 days prior to screening. Hemoglobin ≥80 g/L; neutrophil count \>1.0 × 10\^9/L; platelet count ≥75 × 10\^9/L. 2. Total bilirubin ≤1.5× upper limit of normal (ULN); if liver metastasis or Gilbert's syndrome present, total bilirubin ≤3× ULN. 3. ALT or AST ≤2.5× ULN; if liver metastasis, ALT or AST ≤5× ULN. 4. Serum creatinine (SCr) ≤1.5× ULN or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula). 5. Prothrombin time (PT), International Normalized Ratio (INR) ≤1.5× ULN (unless using warfarin for anticoagulation). 6. Cardiac Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥50%. 7. If the investigator considers any of the above parameters below the study's lower limit due to disease progression, the patient's inclusion can be discussed with the sponsor and the CRO's medical team. 7.No plans for pregnancy during the treatment period. Female patients of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the trial and for 4 months after treatment. 8.Able to understand and voluntarily sign a written informed consent form before the trial. 9.Able to communicate well with the investigator and adhere to the protocol for completing the trial.
Exclusion criteria
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Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ScRNA-seq profiles of tumor tissues before and after injection | If the patient receives personalized treatment, safety follow-up will be conducted 28 days after the last infusion; if not, safety follow-up will be conducted 28 days after the 5th dose. | Analysis of changes in the TME during treatment by comparing scRNA-seq profiles of tumor tissues before and after injection. |
| Clinical data from patients with disease remission (CR/PR) and those without remission (SD/PD) | If the patient receives personalized treatment, safety follow-up will be conducted 28 days after the last infusion; if not, safety follow-up will be conducted 28 days after the 5th dose. | Identification of key molecular mechanisms and immune cell components associated with treatment efficacy by comparing data from patients with disease remission (CR/PR) and those without remission (SD/PD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportions of different immune cell types in tumor tissues from subjects with varying disease remission statuses. | If the patient receives personalized treatment, safety follow-up will be conducted 28 days after the last infusion; if not, safety follow-up will be conducted 28 days after the 5th dose. | (1) Identification of immune cells associated with the formation of immune memory by comparing the proportions of different immune cell types in tumor tissues from subjects with varying disease remission statuses. The molecular mechanisms underlying this process will be explored through gene expression profiling, focusing on key immune cell components and molecular pathways related to T cell memory formation. |
| Gene expression profiling in tumor tissues from subjects with varying disease | If the patient receives personalized treatment, safety follow-up will be conducted 28 days after the last infusion; if not, safety follow-up will be conducted 28 days after the 5th dose. | The molecular mechanisms underlying this process will be explored through gene expression profiling, focusing on key immune cell components and molecular pathways related to T cell memory formation. Identification of endogenous tumor factors associated with immune chemotaxis, T cell activation, and immune escape through correlation analysis with tumor cell characteristics, molecular genetic alterations, and oncogenic pathways. |
| Molecular biological changes in EBV in peripheral blood samples before and after EBV mRNA vaccine injection | Time Frame: If the patient receives personalized treatment, safety follow-up will be conducted 28 days after the last infusion; if not, safety follow-up will be conducted 28 days after the 5th dose. | Analysis of molecular biological changes in EBV in peripheral blood samples before and after EBV mRNA vaccine injection, focusing on changes in genes, proteins, and other molecular markers. |
Countries
China
Contacts
Primary ContactWeili Zhao
Backup ContactPengpeng Xu
Outcome results
None listed