A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of Therapeutic Immunological Agent for EBV Lymphoproliferative Diseases

West China Hospital1 site in 1 country27 target enrollmentOctober 2024

ConditionsCAEBV (Chronic Active Epstein-Barr Virus Infection) Syndrome PTLDs

InterventionsEBV immunological agent

DrugsEBV immunological agent

Overview

Phase: Phase 1
Intervention: EBV immunological agent
Conditions: CAEBV (Chronic Active Epstein-Barr Virus Infection) Syndrome
Sponsor: West China Hospital
Enrollment: 27
Locations: 1
Primary Endpoint: Safety and tolerability
Status: Not yet recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study intends to conduct a prospective single-center open single-arm multi-dose escalation study on therapeutic immunological agent treatment in patients with Lymphoproliferative disease associated with EBV to observe the safety and efficacy.

Registry

clinicaltrials.gov

Start Date

October 2024

End Date

December 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

West China Hospital

Responsible Party

Principal Investigator

Xingchen Peng

professor

West China Hospital

Eligibility Criteria

Inclusion Criteria

•For CAEBV patients and others with EBV-LPD 1). Patients who have signed informed consent before the trial and have a full understanding of the trial content, process and possible adverse reactions, and can complete the study according to the requirements of the trial protocol; 2). Patients with evidence consistent with the following diagnoses:
•a. Patients with the 2016 version of WHO's CAEBV diagnostic criteria (except
•B-lymphocyte involvement only) :
•Persistent or recurrent infectious IM-like symptoms lasting for more than 3 months;
•Increased EBV-DNA load in peripheral blood or tissue lesions: the level of EBV-DNA in peripheral blood was higher than 10\^2.5 copies/μg DNA; ③ EBV-infected T cells or NK cells were found in the affected tissues or peripheral blood;
•④ Exclude other possible diagnoses, such as primary EBV infection (IM), autoimmune diseases, neoplastic diseases, other viral infections (HBV, HIV, HCV, etc.), and congenital or secondary immunodeficiency diseases; Or b. EBV-PLD patients with evidence consistent with pathological diagnosis of EBV antigen positive; 3). Male and female, 2-70 years old (including the critical value); 4). Patients with EBV-DNA≥1000 copies/mL or EBER+; 5). Before the study, total bilirubin ≤ 2 times of the upper limit of normal value, blood creatinine ≤ 1.5 times of normal value; Fibrinogen can be corrected to ≥0.6g/L after infusion.
•. Before the study, hemoglobin ≥60g/L, platelets ≥50×10\^9/L, neutrophil count ≥1×10\^9/L; 7). Echocardiography showed LVEF ≥ 50%; 8). Women of childbearing age must confirm through a pregnancy test that they are not pregnant and be willing to use effective contraception during the test period and for ≥12 months after the last dose; 9). The compliance was good, and the patients and their families were willing to cooperate with the later follow-up.
•For PTLD patients 1). Patients who have signed informed consent before the trial and have a full understanding of the trial content, process and possible adverse reactions, and can complete the study according to the requirements of the trial protocol; 2). Patients diagnosed with PTLD WHO have received SOT or HSCT (refer to WHO 2016 diagnostic criteria); 3). Male and female, 18-70 years old (including the critical value); 4). Patients with EBV-DNA≥1000 copies/mL or EBER+; 5). Women of childbearing age must confirm through a pregnancy test that they are not pregnant and be willing to use effective contraception during the test period and for ≥12 months after the last dose; 6). Good compliance, patients and their families are willing to cooperate with later follow-up.

Exclusion Criteria

•Patients were excluded if they met any of the following criteria:
•For CAEBV patients and others with EBV-LPD 1). Participated in other drug clinical trials within 4 weeks; 2). Pregnant or lactating patients; 3). Patients with severe heart, lung and kidney diseases; 4). Active gastrointestinal bleeding; 5). The patient has active pulmonary tuberculosis, bacterial or fungal infection (≥ Grade 2 of NCI-CTC, 3rd edition); Have a history of herpes simplex, herpes zoster or chickenpox within 3 months; 6). People with a history of psychotropic drug abuse and unable to quit or patients with mental disorders; 7). The subject has any active autoimmune disease or history of autoimmune disease; 8). In the judgment of the investigator, there is a serious concomitant disease that endangers the patient's safety or interferes with the patient's completion of the study.
•For PTLD patients 1). Patients with active aGVHD III-IV and/or mild and severe cGVHD; 2). Had received other cellular immunotherapy clinical studies 30 days before enrollment; 3). Pregnant or lactating patients; 4). Intracranial hypertension or confusion; Respiratory failure; Patients with diffuse intravascular coagulation; 5). Organ failure patients: (1) Heart :NYHA level IV cardiac function; (2) Liver: Grade C, reaching the Child-Turcotte liver function grade; (3) Kidney: renal failure, uremia; (4) Lungs: symptoms of respiratory failure. 6). Patients with active gastrointestinal bleeding; 7). Patients with severe non-compensatory hypertension; 8). Patients with severe non-compensatory diabetes; 9). The patient has active pulmonary tuberculosis, bacterial or fungal infection (≥ Grade 2 of NCI-CTC, 3rd edition); Have a history of herpes simplex, herpes zoster or chickenpox within 3 months; 10). Those who have a history of psychotropic drug abuse and cannot quit or those with mental disorders; 11). The subject has any active autoimmune disease or history of autoimmune disease; 12). Other possible diagnoses, such as primary EBV infection (IM), neoplastic diseases, other viral infections (HBV, HIV, HCV, etc.), and congenital or secondary immunodeficiency diseases; 13). According to the judgment of the investigator, there is a serious harm to the safety of the patient or affect the completion of the study.

Arms & Interventions

Treatment Cohort

EBV immunological agent administration on day 0,7,14,21 and 42 for Intradermal or Subcutaneous Injection

Intervention: EBV immunological agent

Outcomes

Primary Outcomes

Safety and tolerability

Time Frame: up to 12 months

Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).