Clinical Study of Therapeutic Immunological Agent for EBV Lymphoproliferative Diseases

NCT06666153 | Not Yet Recruiting Phase 1

• 1 other identifier: 2024-68
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Quality of life for patients

  up to 12 months

• Effectiveness

  up to 12 months

Study Arms (1)

Treatment Cohort

EXPERIMENTAL

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

Biological: EBV immunological agent

Interventions

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.

Treatment Cohort

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, China

Location

Related Publications (14)

• 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 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.

  PMID: 25735952 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.

  PMID: 12393655 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.

  PMID: 21361747 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.

  PMID: 36969150 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.

  PMID: 34552486 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.

  PMID: 26205347 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.

  PMID: 23737188 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.

  PMID: 20498651 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.

  PMID: 28210942 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.

  PMID: 19236801 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.

  PMID: 12599068 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.

  PMID: 32598475 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.

  PMID: 11435294 RESULT

MeSH Terms

Conditions

Syndrome; Lymphoproliferative Disorders

Condition Hierarchy (Ancestors)

Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xingchen Peng

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng

CONTACT

+86 18980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: October 28, 2024
• First Posted: October 30, 2024
• Study Start: October 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 30, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)