Clinical and Biological Cohort Study of EBV-Positive T/NK-Cell Lymphoproliferative Diseases

Официальное название

A Multicenter Ambidirectional Clinical and Biological Cohort Study of Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Diseases

Обзор

This is a multicenter, non-interventional, ambidirectional cohort study of Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases. The study consists of a retrospective clinical cohort of 500 consecutively diagnosed patients with extranodal NK/T-cell lymphoma and a prospective clinical-biological cohort of 1,000 newly diagnosed patients with extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, systemic chronic active Epstein-Barr virus disease of T/NK-cell type, or Epstein-Barr virus-positive nodal T/NK-cell lymphoma. The study will characterize clinical features, treatment pathways, response, relapse or progression patterns, and long-term survival. The prospective cohort will additionally undergo standardized collection of peripheral blood and optional tumor tissue specimens at predefined clinical time points. Clinical, molecular, viral, and immune biomarkers will be evaluated for their associations with treatment response, treatment failure, disease progression, and survival. No treatment is assigned by the study.

Подробное описание

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases comprise a heterogeneous spectrum of disorders that share viral and immunobiological features but differ substantially in clinical presentation, disease course, treatment, and prognosis. Extranodal NK/T-cell lymphoma is the principal disease entity in this study and will constitute the core population for clinical outcome analyses and development of integrated clinical-molecular prognostic models.

The study includes two cohorts. Cohort A is a retrospective cohort of approximately 500 consecutive hospitalized patients with newly diagnosed extranodal NK/T-cell lymphoma diagnosed between January 1, 2020 and December 31, 2025. Patients are identified through pathology records, followed by clinical verification and confirmation of survival follow-up. Cohort A includes clinical data only.

Cohort B is a prospective clinical-biological cohort of approximately 1,000 consecutive newly diagnosed patients enrolled between June 1, 2026 and December 31, 2030. Eligible disease entities include extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, systemic chronic active Epstein-Barr virus disease of T/NK-cell type, and Epstein-Barr virus-positive nodal T/NK-cell lymphoma. Extranodal NK/T-cell lymphoma will account for at least 80% of Cohort B.

Treatment is determined by treating physicians according to routine clinical practice and is not assigned by the study. Clinical information includes baseline disease characteristics, pathology, laboratory and imaging findings, treatment exposures, response assessments, adverse events, relapse or progression, subsequent treatment, and survival.

Prospective participants provide a 10-mL peripheral blood sample before treatment and are scheduled for additional sample collection after two treatment cycles, at the end of treatment or first formal end-of-treatment assessment, and at relapse or refractory disease confirmation. Plasma and peripheral blood mononuclear cells are stored in two aliquots at participating-center biobanks. Tumor tissue is optional. Molecular, viral, immune, and tumor microenvironment analyses will be performed within the scope approved by the protocol and informed consent.

The main clinical outcomes are overall survival and progression-free survival. Secondary outcomes include objective response rate, complete response rate, primary refractory disease, early progression, relapse or progression patterns, post-relapse survival, grade 3 or higher adverse events, serious infections, treatment-related mortality, and longitudinal changes in plasma Epstein-Barr virus DNA, circulating tumor DNA, and immune biomarkers.

Первичные конечные точки

• Overall Survival [Срок оценки: From initial diagnosis to death or last confirmed follow-up, assessed for up to 10 years.]
• Progression-Free Survival [Срок оценки: From initial diagnosis to progression, relapse, death, or last disease assessment, assessed for up to 10 years.]

Вторичные конечные точки (4)

• Objective Response Rate [Срок оценки: From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months.]
• Complete Response Rate [Срок оценки: From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months.]
• Grade 3 or Higher Adverse Events [Срок оценки: During each treatment line, from treatment initiation through treatment completion, assessed for up to 24 months per treatment line.]
• Treatment-Related Mortality [Срок оценки: From initiation of first anticancer treatment to 30 days after the last administered treatment, assessed for up to 10 years across treatment lines.]

Критерии участия

Критерии включения

• Age 18 years or older.
• Newly diagnosed Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease meeting World Health Organization diagnostic criteria.
• For the retrospective cohort: diagnosis of extranodal NK/T-cell lymphoma between January 1, 2017 and December 31, 2025 at a participating center.
• For the prospective cohort: diagnosis between June 1, 2026 and December 31, 2030 of one of the following:
• Extranodal NK/T-cell lymphoma;
• Aggressive NK-cell leukemia;
• Systemic chronic active Epstein-Barr virus disease of T/NK-cell type; or Epstein-Barr virus-positive nodal T/NK-cell lymphoma.
• Availability of essential diagnostic, staging, and treatment information.
• For the prospective cohort: written informed consent and successful collection of the protocol-required baseline peripheral blood specimen.

Критерии исключения

• For the retrospective cohort: no usable survival follow-up information, inability to confirm survival status, or inability to calculate the principal survival outcomes.
• For the prospective cohort: unwillingness or inability to participate in protocol-defined longitudinal clinical follow-up.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Публикации

• Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; Germ PMID 25113753
• Li D, Liu C, Wan J, Zhang W, Ma Y, Zhu Y, Ma L, Tian S, Ding H, Tao R. Sintilimab, pegaspargase, and anlotinib as induction therapy for advanced-stage NKTCL: a multicenter phase II study. Blood Adv. 2026 Mar 3:bloodadvances.2025018720. doi: 10.1182/bloodadvances.2025018720. Online ahead of print. PMID 41774854
• Zhu Y, Tian S, Xu L, Ma Y, Zhang W, Wang L, Jin L, Liu C, Zhu C, Li Z, Hao S, Zhong H, Ding H, Tao R. GELAD chemotherapy with sandwiched radiotherapy for patients with newly diagnosed stage IE/IIE natural killer/T-cell lymphoma: a prospective multicentre study. Br J Haematol. 2022 Feb;196(4):939-946. doi: 10.1111/bjh.17960. Epub 2021 Nov 21. PMID 34806163
• Liu C, Ding H, Zhu Q, Liu P, Zhu Y, Wang L, Ma Y, Zhang W, Tian S, Zhang X, Jin L, Liu L, Li Z, Hao S, Tao R. Induction with MEDA regimen and consolidation with Auto-HSCT for stage IV NKTCL patients: A prospective multicenter study. Int J Cancer. 2022 Sep 1;151(5):752-763. doi: 10.1002/ijc.34055. Epub 2022 Jun 9. PMID 35489026
• Oishi N, Ahmed R, Feldman AL. Updates in the Classification of T-cell Lymphomas and Lymphoproliferative Disorders. Curr Hematol Malig Rep. 2023 Dec;18(6):252-263. doi: 10.1007/s11899-023-00712-9. Epub 2023 Oct 23. PMID 37870698
• Luniewski A, Chaudhary S, Goldfarb A, Obiorah IE. EBV-Driven NK/T-Cell Lymphoproliferative Disorders: Clinical Diversity and Molecular Insights. Lymphatics. 2026 Mar;4(1):7. doi: 10.3390/lymphatics4010007. Epub 2026 Jan 26. PMID 41657941

Идентификаторы

NCT: NCT07727083 · SHCA-EBV-T/NK-202601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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