Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma (TOXNHL)

June 11, 2026 updated by: Henry M. Jackson Foundation for the Advancement of Military Medicine

Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma Across the Military Healthcare System

The goal of this observational cohort study is to learn how toxin and occupational exposures, germline genetic variation, and immune dysregulation relate to B-cell non-Hodgkin lymphoma among active-duty service members and other Military Health System beneficiaries. The main questions are whether specific exposures and germline variants are associated with B-cell NHL subtype, immune dysfunction, and clinical outcomes. Participants will complete exposure and medical-history surveys, provide biospecimens for immune and genomic testing, and may be followed annually for up to 3 years.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This prospective observational registry and biorepository study evaluates the relationship between occupational/environmental toxin exposures, immune dysregulation, and germline genetic susceptibility in active-duty service members (ADSMs) and other Military Health System (MHS) beneficiaries with B-cell non-Hodgkin lymphoma (NHL). Participants will be enrolled into one of three cohorts based on disease status and age, including individuals in remission, newly diagnosed adults, and treatment-naïve pediatric patients.

The study will collect clinical, epidemiologic, immunologic, and genomic data longitudinally for up to 3 years. Participants will complete standardized surveys assessing demographics, military history, occupational/environmental exposures, medical history, and family history. Additional military exposure data may be obtained from the Department of Defense Individual Longitudinal Exposure Record (ILER).

Clinical data abstracted from the electronic medical record will include lymphoma subtype, staging, pathology, treatment history, laboratory values, infectious complications, immune phenotyping, treatment response, recurrence, second malignancies, and survival outcomes.

Biospecimens may include peripheral blood, skin fibroblasts, residual tumor tissue, bone marrow aspirate, and archived serum samples from the Department of Defense Serum Repository (DODSR). Germline and somatic genomic analyses will be performed using next-generation sequencing platforms, including whole genome sequencing. Immunologic analyses may include lymphocyte subsets, B-cell phenotyping, T-cell phenotyping, activation markers, cytokine profiling, and functional immune assays.

The primary objectives are to characterize toxin exposures and immune dysregulation in B-cell NHL, identify germline pathogenic variants associated with lymphoma susceptibility, and establish a comprehensive longitudinal database and biospecimen repository for future translational research. Exploratory analyses will evaluate relationships among environmental exposures, genomic variants, immune phenotypes, lymphoma subtype, and clinical outcomes.

Study Type

Observational

Enrollment (Estimated)

300

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

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20814
        • Recruiting
        • Walter Reed National Military Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jeremy Perkins, MD, FACP, COL, US Army (ret)
      • Bethesda, Maryland, United States, 20814
        • Active, not recruiting
        • Uniformed Services University of the Health Sciences
    • Virginia
      • Portsmouth, Virginia, United States, 23708
        • Active, not recruiting
        • Naval Medical Center Portsmouth

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Active-duty service members and other MHS beneficiaries, ages 4 years old and up, with B-cell NHL recruited from WRNMMC/Murtha Cancer Center, adult/pediatric Hematology-Oncology clinics, Allergy/Immunology clinic, screening from existing clinical patient lists, and associated MHS sites.

Description

Inclusion Criteria:

  • Age 4 years old and older with a clinical diagnosis of B-cell NHL.
  • Must be willing to undergo phlebotomy and/or skin punch biopsy.
  • Must be willing to undergo whole genome sequencing, which includes return of primary and secondary findings.

Exclusion Criteria:

  • Has any condition that, in the opinion of the Principal Investigator, contraindicates participation in this study. Examples of situation that may contraindicate participation include but are not limited to a) some cases of cerebral vascular accidents where an individual no longer has the capacity to make their own medical decisions and a conservator or responsible family member is not available and b) an individual has active suicidal ideation and is a danger to themselves at the time of enrollment.
  • Does not have access to health care and primary care clinician.
  • Actively undergoing induction treatment for NHL.

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
Cohort 1
Active duty service members (ADSMs) and other Military Health System (MHS) beneficiaries who have a history of B-cell non-Hodgkin Lymphoma (NHL) and have achieved clinical remission.
Cohort 2
ADSMs and other MHS beneficiaries ages 18 and older who are newly diagnosed with B-cell NHL and/or are not undergoing active treatment.
Cohort 3
Other MHS beneficiaries ages 4-17 who are diagnosed with B-cell NHL and are treatment naive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aim 1: Characterize occupational exposures and their impact on health outcomes and immune health of ADSMs and other MHS beneficiaries with B-cell NHL.
Time Frame: 3 years
  1. Characterize and determine the prevalence of various toxin and occupational exposures in ADSMs and other MHS beneficiaries with B-cell NHL (Cohorts 1-3).
  2. Characterize the B-cell NHL subtypes and health outcomes of NHL in ADSMs and other MHS beneficiaries (Cohorts 1-3).
  3. Characterize immune dysregulation in ADSMs and other MHS beneficiaries with B-cell NHL. Immune dysregulation could be characterized by humoral vs cellular defects as well as innate vs adaptive defects among others (Cohorts 2-3).
3 years
Aim 2: Identify and interpret germline variants in ADSMs and other MHS beneficiaries with B-cell NHL.
Time Frame: 3 years
1. Determine the relative frequency of germline pathogenic/likely pathogenic variants in MHS beneficiaries with B-cell NHL (Cohorts 1-3).
3 years
Aim 3: Create a comprehensive database and biorepository of ADSMs and other MHS beneficiaries with B-cell NHL.
Time Frame: 3 years
  1. Create a database compiling clinical information, toxin exposure, military history (if applicable), and health outcomes (Cohorts 1-3).
  2. Create a biorespository of peripheral blood (Cohorts 1-3).
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory Endpoints
Time Frame: 3 years
  1. Determine the relative frequency of somatic tumor mutations in MHS beneficiaries and analyze the association with germline variants (Cohorts 1-3).
  2. Characterize pre-diagnostic serum of ADSMs and analyze their association with clinical outcomes, tumor subtype, and subsequent immune dysregulation.
3 years

Collaborators and Investigators

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

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborators

Children's Hospital Medical Center, Cincinnati
Walter Reed National Military Medical Center
Uniformed Services University of the Health Sciences
United States Naval Medical Center, Portsmouth
Murtha Cancer Center
The American Genome Center

Investigators

  • Principal Investigator: Christin Destefano, Uniformed Services University of the Health Sciences

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 (Actual)

May 1, 2025

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

June 11, 2026

First Submitted That Met QC Criteria

June 11, 2026

First Posted (Actual)

June 17, 2026

Study Record Updates

Last Update Posted (Actual)

June 17, 2026

Last Update Submitted That Met QC Criteria

June 11, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • USUHS.2024-137
  • HU00012520036 (Other Grant/Funding Number: Uniformed Services University of the Health Sciences)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Coded/de-identified study data and biospecimen-associated data may be shared with approved collaborators or public/controlled repositories using external study/sample IDs and appropriate data-sharing agreements; direct identifiers will not be shared. Data shared via cBioPortal as well as by formal request with appropriate agreements in place.

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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