Clinical trial NCT06666153: Clinical Study of Therapeutic Immunological Agent for EBV Lymphoproliferative Diseases
Official title: A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of Therapeutic Immunological Agent for EBV Lymphoproliferative Diseases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: CAEBV (Chronic Active Epstein-Barr Virus Infection) Syndrome
PTLDs
Keywords: EBV
immunotherapy
Lymphoproliferative disease, LPD
chronic active Epstein-Barr virus disease，CAEBV
Post-transplant lymphoproliferative disorders，PTLD
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2024-10-30
Enrollment: 27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Safety and tolerability
timeFrame: up to 12 months
Secondary outcomes:
measure: Quality of life for patients
timeFrame: up to 12 months
measure: Effectiveness
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Xingchen Peng
role: PRINCIPAL_INVESTIGATOR
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