clinical study of therapeutic immunological agent for ebv lymphoproliferative diseases

Conditions: CAEBV (Chronic Active Epstein-Barr Virus Infection) Syndrome; PTLDs

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.


Eligibility criteria:
inclusion criteria: 1. 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. 6). 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. 2. 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: 1. 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. 2. 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.

Keywords: ebv immunotherapy lymphoproliferative disease, lpd chronic active epstein-barr virus disease，caebv post-transplant lymphoproliferative disorders，ptld