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

July 22, 2026 updated by: Rong Tao

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

1500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Fudan University Shanghai Cancer Center
        • Principal Investigator:
          • Rong Tao, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From initial diagnosis to death or last confirmed follow-up, assessed for up to 10 years.
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
Time Frame: From initial diagnosis to progression, relapse, death, or last disease assessment, assessed for up to 10 years.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months.
The proportion of response-evaluable participants who achieve a best response of complete response or partial response during first-line treatment. The response-evaluable population includes participants who undergo at least one formal response assessment.
From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months.
Complete Response Rate
Time Frame: From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months.
The proportion of response-evaluable participants who achieve complete response during first-line treatment.
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
Time Frame: During each treatment line, from treatment initiation through treatment completion, assessed for up to 24 months per treatment line.
The proportion of participants experiencing grade 3 or higher adverse events during systemic anticancer treatment, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
During each treatment line, from treatment initiation through treatment completion, assessed for up to 24 months per treatment line.
Treatment-Related Mortality
Time Frame: From initiation of first anticancer treatment to 30 days after the last administered treatment, assessed for up to 10 years across treatment lines.
The proportion of participants whose death is assessed as related to anticancer treatment.
From initiation of first anticancer treatment to 30 days after the last administered treatment, assessed for up to 10 years across treatment lines.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma Epstein-Barr Virus (EBV) DNA Level
Time Frame: Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.
Plasma Epstein-Barr virus (EBV) DNA level (Copies/mL) will be quantitatively measured by real-time polymerase chain reaction (PCR) at predefined clinical time points in the prospective cohort.
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
Time Frame: Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.
The presence or absence of tumor-derived somatic mutations detected in circulating tumor DNA will be evaluated by next-generation sequencing at predefined clinical time points.
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
Time Frame: Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.
Frequencies of immune cell subsets in peripheral blood, including EBV-infected cell subsets when applicable, will be evaluated by flow cytometry at predefined clinical time points.
Baseline, after 2 treatment cycles, at end of treatment, and at relapse or refractory disease confirmation; assessed for up to 10 years.
Peripheral Blood Cytokine Concentrations
Time Frame: Baseline, after 2 treatment cycles, at end of treatment or formal end-of-treatment assessment, and at relapse or refractory disease confirmation; assessed for up to 10 years.
Peripheral Blood Cytokine Concentrations
Baseline, after 2 treatment cycles, at end of treatment or formal end-of-treatment assessment, and at relapse or refractory disease confirmation; assessed for up to 10 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rong Tao

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 25, 2026

Primary Completion (Estimated)

December 31, 2035

Study Completion (Estimated)

December 31, 2035

Study Registration Dates

First Submitted

July 19, 2026

First Submitted That Met QC Criteria

July 22, 2026

First Posted (Actual)

July 27, 2026

Study Record Updates

Last Update Posted (Actual)

July 27, 2026

Last Update Submitted That Met QC Criteria

July 22, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHCA-EBV-T/NK-202601

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Individual participant data will not be made publicly available because the current informed consent and multicenter data governance framework do not authorize unrestricted public sharing. Deidentified data may be considered for qualified scientific requests subject to approval by the study steering committee, participating institutions, and applicable ethics committees.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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