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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Cohort | Experimental | EBV immunological agent administration on day 0,7,14,21 and 42 for Intradermal or Subcutaneous Injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EBV immunological agent | Biological | 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 one dose will be administered to each participant with EBV immunological agent combined with Toripalimab 240mg. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability | 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). | up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Quality of life for patients | The EORTC QLQ-C30 consists of five functional scales, nine symptom scales and one global quality of life (QoL) scale, and has been validated in an international setting | up to 12 months |
| Effectiveness |
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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.
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.
Exclusion Criteria:
Patients were excluded if they met any of the following criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xingchen Peng | Contact | +86 18980606753 | pxx2014@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Xingchen Peng | West China Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital | Chengdu | Sichuan | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36556158 | Result | 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. | |
| 25735952 | Result | 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. |
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| ID | Term |
|---|---|
| D013577 | Syndrome |
| D008232 | Lymphoproliferative Disorders |
| ID | Term |
|---|---|
| D004194 | Disease |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008206 | Lymphatic Diseases |
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|
The number of subjects with CR and PR, calculate the duration from the time of initial administration to the date of disease progression or the date of subject's death
| up to 12 months |
| 12393655 | Result | 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. |
| 21361747 | Result | 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. |
| 36969150 | Result | 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. |
| 34552486 | Result | 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. |
| 26205347 | Result | 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. |
| 23737188 | Result | 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. |
| 20498651 | Result | Kawa K, Sawada A, Sato M, Okamura T, Sakata N, Kondo O, Kimoto T, Yamada K, Tokimasa S, Yasui M, Inoue M. Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection. Bone Marrow Transplant. 2011 Jan;46(1):77-83. doi: 10.1038/bmt.2010.122. Epub 2010 May 24. |
| 28210942 | Result | Sawada A, Inoue M, Kawa K. How we treat chronic active Epstein-Barr virus infection. Int J Hematol. 2017 Apr;105(4):406-418. doi: 10.1007/s12185-017-2192-6. Epub 2017 Feb 16. |
| 19236801 | Result | Lu G, Xie ZD, Zhao SY, Ye LJ, Wu RH, Liu CY, Yang S, Jin YK, Shen KL. Clinical analysis and follow-up study of chronic active Epstein-Barr virus infection in 53 pediatric cases. Chin Med J (Engl). 2009 Feb 5;122(3):262-6. |
| 12599068 | Result | Kimura H, Morishima T, Kanegane H, Ohga S, Hoshino Y, Maeda A, Imai S, Okano M, Morio T, Yokota S, Tsuchiya S, Yachie A, Imashuku S, Kawa K, Wakiguchi H; Japanese Association for Research on Epstein-Barr Virus and Related Diseases. Prognostic factors for chronic active Epstein-Barr virus infection. J Infect Dis. 2003 Feb 15;187(4):527-33. doi: 10.1086/367988. Epub 2003 Jan 28. |
| 32598475 | Result | Yonese I, Sakashita C, Imadome KI, Kobayashi T, Yamamoto M, Sawada A, Ito Y, Fukuhara N, Hirose A, Takeda Y, Makita M, Endo T, Kimura SI, Ishimura M, Miura O, Ohga S, Kimura H, Fujiwara S, Arai A. Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification. Blood Adv. 2020 Jul 14;4(13):2918-2926. doi: 10.1182/bloodadvances.2020001451. |
| 11435294 | Result | Kimura H, Hoshino Y, Kanegane H, Tsuge I, Okamura T, Kawa K, Morishima T. Clinical and virologic characteristics of chronic active Epstein-Barr virus infection. Blood. 2001 Jul 15;98(2):280-6. doi: 10.1182/blood.v98.2.280. |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |