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

NCT07727083 | Recruiting

• 1 other identifier: SHCA-EBV-T/NK-202601
• Study Type: observational
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Extranodal NK/T-cell Lymphoma; Aggressive NK-Cell Leukemia; Systemic Chronic Active Epstein-Barr Virus Disease; Epstein-Barr Virus-Positive Nodal T/NK-Cell Lymphoma; Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disease

Keywords

Epstein-Barr virus; T/NK-cell lymphoproliferative disease; extranodal NK/T-cell lymphoma; aggressive NK-cell leukemia; chronic active Epstein-Barr virus disease; EBV-positive nodal T/NK-cell lymphoma; circulating tumor DNA; plasma EBV-DNA; immune profiling; molecular biomarker

Outcome Measures

Primary Outcomes (2)

• Overall Survival

  Overall survival is defined as the time from the date of initial diagnosis to death from any cause. Participants who are alive will be censored at the date on which their survival status was last confirmed.

  From initial diagnosis to death or last confirmed follow-up, assessed for up to 10 years.

• Progression-Free Survival

  Progression-free survival is defined as the time from the date of initial diagnosis to the first documented disease progression, disease relapse, or death from any cause, whichever occurs first. Participants without an event will be censored at the date of the last assessment confirming absence of progression.

  From initial diagnosis to progression, relapse, death, or last disease assessment, assessed for up to 10 years.

Secondary Outcomes (4)

• Objective Response Rate

  From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months.

• Complete Response Rate

  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

  During each treatment line, from treatment initiation through treatment completion, assessed for up to 24 months per treatment line.

• Treatment-Related Mortality

  From initiation of first anticancer treatment to 30 days after the last administered treatment, assessed for up to 10 years across treatment lines.

Other Outcomes (4)

• Plasma Epstein-Barr Virus (EBV) DNA Level

  Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.

• Circulating Tumor DNA Mutation Detection Status

  Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.

• Peripheral Blood Immune Cell Subset Frequencies

  Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.

Study Arms (2)

Retrospective NKTCL Cohort

Approximately 500 consecutive hospitalized patients with newly diagnosed extranodal NK/T-cell lymphoma diagnosed between January 1, 2017 and December 31, 2025. Clinical, treatment, response, relapse, safety, and survival information is collected from medical records and follow-up records. No biospecimen collection is mandated.

Prospective EBV-Positive T/NK Disease Cohort

Approximately 1,000 consecutive newly diagnosed patients enrolled between June 1, 2026 and December 31, 2030. Eligible diseases 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. Clinical information, longitudinal outcomes, and protocol-defined biospecimens are collected. Extranodal NK/T-cell lymphoma will represent at least 80% of this cohort.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18 years or older with a newly diagnosed Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease meeting World Health Organization diagnostic criteria. The retrospective cohort includes consecutive hospitalized patients with extranodal NK/T-cell lymphoma diagnosed from 2017 through 2025. The prospective cohort includes consecutive newly diagnosed patients with extranodal NK/T-cell lymphoma or one of the prespecified rare Epstein-Barr virus-positive T/NK-cell disease entities from 2026 through 2030.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rong Tao: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (6)

• 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; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.

  PMID: 25113753 BACKGROUND

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples are collected prospectively before treatment, after two treatment cycles, at the end of treatment or the first formal end-of-treatment assessment, and at relapse or refractory disease confirmation. Each 10-mL blood sample is processed into plasma and peripheral blood mononuclear cells and stored in two aliquots at participating-center biobanks. Optional tumor tissue specimens, preferentially 10-20 unstained slides and no fewer than 5 slides when available, may also be stored. Specimens will be used only for protocol-specified EBV-DNA, circulating tumor DNA, molecular genetic, immune profiling, cytokine, EBV-infected cell subset, and tumor microenvironment analyses.

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Leukemia, Large Granular Lymphocytic; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Central Study Contacts

Rong Tao, MD

CONTACT

008621-64175590; hkutao@hotmail.com

Chuanxu Liu, MD

CONTACT

008621-64175590; liuchaunxu@shca.or.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Department head, professor

Study Record Dates

• First Submitted: July 19, 2026
• First Posted: July 27, 2026
• Study Start: August 11, 2026
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035
• Last Updated: August 13, 2026

Record last verified: 2026-08

Locations

CN (1)