Clinical Study of Therapeutic Immunological Agent for EBV Lymphoproliferative Diseases

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат EBV immunological agent
  27 participants with will be enrolled in the study and divided into three groups, including EBV-LPD (Adults group), EBV-LPD (Children group) and PTLD (Adults group） each with 9 people.The participants will be divided into three different dose groups, and a "3+3" dose escalation design is used. The low dose is 5.0×10\^5, the medium dose is 2.0×10\^6 and the high dose is 5.0×10\^6 for children and low dose is 5.0×10\^6, the medium dose is 2.0×10\^7 and the high dose is 5.0×10\^7 for adults. Only o

Первичные конечные точки

• Safety and tolerability [Срок оценки: up to 12 months]

Вторичные конечные точки (2)

• Quality of life for patients [Срок оценки: up to 12 months]
• Effectiveness [Срок оценки: up to 12 months]

Критерии участия

Критерии включения

• 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.

• 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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital — Чэнду

Публикации

• Clerico M, Dogliotti I, Aroldi A, Consoli C, Giaccone L, Bruno B, Cavallo F. Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Stem Cell Transplantation: Biology and Treatment Options. J Clin Med. 2022 Dec 19;11(24):7542. doi: 10.3390/jcm11247542. PMID 36556158
• Hartlage AS, Liu T, Patton JT, Garman SL, Zhang X, Kurt H, Lozanski G, Lustberg ME, Caligiuri MA, Baiocchi RA. The Epstein-Barr Virus Lytic Protein BZLF1 as a Candidate Target Antigen for Vaccine Development. Cancer Immunol Res. 2015 Jul;3(7):787-94. doi: 10.1158/2326-6066.CIR-14-0242. Epub 2015 Mar 3. PMID 25735952
• Savoldo B, Huls MH, Liu Z, Okamura T, Volk HD, Reinke P, Sabat R, Babel N, Jones JF, Webster-Cyriaque J, Gee AP, Brenner MK, Heslop HE, Rooney CM. Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection. Blood. 2002 Dec 1;100(12):4059-66. doi: 10.1182/blood-2002-01-0039. Epub 2002 Aug 1. PMID 12393655
• Bollard CM, Gottschalk S, Helen Huls M, Leen AM, Gee AP, Rooney CM. Good manufacturing practice-grade cytotoxic T lymphocytes specific for latent membrane proteins (LMP)-1 and LMP2 for patients with Epstein-Barr virus-associated lymphoma. Cytotherapy. 2011 May;13(5):518-22. doi: 10.3109/14653249.2011.561983. Epub 2011 Mar 1. No abstract available. PMID 21361747
• Ma Y, Zhang P, Bao Y, Luo H, Wang J, Huang L, Zheng M. Outcomes of programmed death protein-1 inhibitors treatment of chronic active Epstein Barr virus infection: A single center retrospective analysis. Front Immunol. 2023 Mar 10;14:1093719. doi: 10.3389/fimmu.2023.1093719. eCollection 2023. PMID 36969150
• Song Y, Wang J, Wang Y, Wang Z. Ruxolitinib in Patients With Chronic Active Epstein-Barr Virus Infection: A Retrospective, Single-Center Study. Front Pharmacol. 2021 Sep 6;12:710400. doi: 10.3389/fphar.2021.710400. eCollection 2021. PMID 34552486
• Hui KF, Cheung AK, Choi CK, Yeung PL, Middeldorp JM, Lung ML, Tsao SW, Chiang AK. Inhibition of class I histone deacetylases by romidepsin potently induces Epstein-Barr virus lytic cycle and mediates enhanced cell death with ganciclovir. Int J Cancer. 2016 Jan 1;138(1):125-36. doi: 10.1002/ijc.29698. Epub 2015 Aug 11. PMID 26205347
• Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013 Sep;8(3):173-83. doi: 10.1007/s11899-013-0162-5. PMID 23737188

Идентификаторы

NCT: NCT06666153 · 2024-68

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗