This is an investigator-initiated, open-label, single-arm, dose-escalation exploratory study to evaluate the safety, tolerability, and preliminary efficacy of EBV-AST cell injection in adults with EBV-associated lymphoproliferative disorders, including post-transplant lymphoproliferative disease (PTLD) and EBV-positive lymphomas. Participants will receive EBV-AST cell infusions intravenously every 2 weeks for up to 3 infusions at escalating dose levels. The primary objective is to assess safety and determine a potential optimal biologically active dose. Secondary objectives include preliminary tumor response and EBV-related virologic outcomes, as well as cellular PK/PD.
EBV-associated lymphoproliferative disorders (LPD), including PTLD and EBV-positive lymphomas, are clinically challenging and may occur in immunocompromised or heavily treated patients. EBV-AST is a cellular immunotherapy consisting of EBV antigen-specific cytotoxic T lymphocytes generated by ex vivo stimulation and expansion of T cells using antigen peptide-loaded dendritic cells. After infusion, EBV-AST cells are expected to recognize and eliminate EBV-infected or EBV-antigen-expressing target cells and provide EBV-specific immune reconstitution. This investigator-initiated, open-label, single-arm exploratory study uses a dose-escalation design to evaluate EBV-AST cell injection in adults with EBV-associated LPD. Approximately 4-18 participants will be enrolled across three dose levels (3×10\^5, 3×10\^6, and 3×10\^7 cells/kg per infusion). EBV-AST will be administered by intravenous infusion every 2 weeks for up to three infusions, following protocol-defined escalation rules and DLT assessment within 28 days after the first infusion. Participants will be monitored for adverse events and immune-related toxicities, and assessed for preliminary efficacy (tumor response and EBV-DNA/virologic outcomes) and cellular PK/PD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
EBV-AST is an Epstein-Barr virus (EBV) antigen-specific cytotoxic T-lymphocyte product generated by ex vivo stimulation and expansion of T cells using peptide-loaded dendritic cells. EBV-AST is administered by intravenous infusion every 2 weeks for up to 3 infusions at escalating dose levels (3×10\^5, 3×10\^6, or 3×10\^7 cells/kg per infusion), according to the protocol-defined dose-escalation design.
Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGDose-Limiting Toxicities (DLTs)
Number of participants experiencing dose-limiting toxicities (DLTs) within 28 days after the first EBV-AST cell infusion, as defined by protocol-specific criteria and graded according to NCI CTCAE v5.0.
Time frame: From first infusion (Day 0) through Day 28
Safety: Incidence of Adverse Events
Number of participants with treatment-emergent adverse events (AEs), immune-related adverse events (irAEs), and serious adverse events (SAEs), graded according to NCI CTCAE v5.0, including clinically significant laboratory abnormalities.
Time frame: From first infusion (Day 0) through 12 months after first infusion
Recommended/Optimal Biologically Active Dose (OBD)
Recommended/optimal biologically active dose (OBD) of EBV-AST, determined based on the incidence of DLTs, overall safety profile, and tolerability across dose levels.
Time frame: Up to 28 days after first infusion for DLT evaluation; overall dose decision through study completion
Objective Response Rate (ORR)
Objective response rate (ORR), defined as the proportion of participants achieving complete response (CR) or partial response (PR) according to protocol-defined response criteria.
Time frame: From first infusion (Day 0) through 12 months after first infusion
Disease Control Rate (DCR)
Disease control rate (DCR), defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to protocol-defined criteria.
Time frame: From first infusion (Day 0) through 12 months after first infusion
Progression-Free Survival (PFS)
Progression-free survival (PFS), defined as the time from first EBV-AST infusion to documented disease progression or death from any cause.
Time frame: From first infusion (Day 0) through 12 months after first infusion
Overall Survival (OS)
Overall survival (OS), defined as the time from first EBV-AST infusion to death from any cause.
Time frame: From first infusion (Day 0) through 12 months after first infusion
Duration of Response (DOR)
Duration of response (DOR), defined as the time from first documented complete or partial response to disease progression or death.
Time frame: From first documented response through 12 months after first infusion
EBV-DNA Negativity Rate
Proportion of participants achieving EBV-DNA negativity in peripheral blood as measured by quantitative polymerase chain reaction (qPCR).
Time frame: From first infusion (Day 0) through 12 months after first infusion
Time to EBV-DNA Negativity
Time from first EBV-AST infusion to first documented EBV-DNA negativity in peripheral blood.
Time frame: From first infusion (Day 0) through 12 months after first infusion
Change in EBV-DNA Level
Change from baseline in EBV-DNA levels in peripheral blood over time, as measured by quantitative polymerase chain reaction (qPCR).
Time frame: From baseline through 12 months after first infusion
Maximum Concentration (Cmax) of EBV-AST Cells in Peripheral Blood
The highest measured absolute concentration of viable EBV-AST cells in peripheral blood following infusion, quantified by flow cytometry.
Time frame: From first infusion (Day 0) through Day 28
Concentration of EBV-AST Cells in Peripheral Blood (Cmax)
Maximum absolute concentration of viable EBV-AST cells in peripheral blood post-infusion, quantified by flow cytometry. Unit of Measure: viable EBV-AST cells per microliter (cells/μL).
Time frame: From baseline through Day 28 after first infusion
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