ClinicalTrials.gg
RecruitingNCT07652580TOXNHLUpdated Sep 3, 2026

Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma

An observational study in Non-Hodgkin Lymphoma, Lymphoma Non-Hodgkin and B-cell Lymphoma, sponsored by Henry M. Jackson Foundation for the Advancement of Military Medicine. Recruiting at 3 sites in United States. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2026-09-03.

Primary conditionLymphoma, B-CellRegistry: Lymphoma, Non-HodgkinReclassifiedWhy we changed it
Registry
Lymphoma, Non-Hodgkin — the first condition term the registry derived for this study.
ClinicalTrials.gg
Lymphoma, B-Cell
Why
  1. The study's listed conditions name Lymphoma, B-Cell, a narrower term within Lymphoma, Non-Hodgkin.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by Henry M. Jackson Foundation for the Advancement of Military Medicine · Observational

From the registry’s dates

  • Started May 2025; still recruiting 1 year 6 months later.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
300
Ages
4 Years and older
Sex
All
01

Study summary

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.

Read the 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.

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Conditions studied

  • Non-Hodgkin Lymphoma
  • Lymphoma Non-Hodgkin
  • B-cell Lymphoma
  • Immune Dysregulation

Keywords

  • Immunodeficiency
  • Lymphoma
  • Exposure
  • Genetics
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In context

Lymphoma, B-Cell Reclassified

885 studies on the registry are indexed under Lymphoma, B-Cell; 286 are open to participants now.

This study's planned enrollment of 300 is above the median of 150 across 69 observational studies indexed under Lymphoma, B-Cell.

Browse Lymphoma, B-Cell studies →

Lead sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine is the lead sponsor of 86 studies on the registry; 18 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 2 (29%) have results posted.

Compared within Lymphoma, B-Cell, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Lymphoma, Non-Hodgkin. The counts are of registry records indexed under each term, refreshed daily. How we classify →

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Who can participate

Ages eligible
4 Years and older
Sexes eligible
All
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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 .
  • Must be willing to undergo whole genome sequencing, which includes return of primary and secondary findings.

Exclusion criteria

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.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
300 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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 that is untreated or NHL that has been previously treated.

  • Cohort 3

    Other MHS beneficiaries ages 4-17 who are newly diagnosed with B-cell NHL or are untreated.

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What researchers measure

Primary outcomes

  1. Aim 1: Characterize occupational exposures and their impact on health outcomes and immune health of ADSMs and other MHS beneficiaries with B-cell NHL.

    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).

    Time frame: 3 years

  2. Aim 2: Identify and interpret germline variants in ADSMs and other MHS beneficiaries with B-cell NHL.

    1\. Determine the relative frequency of germline pathogenic/likely pathogenic variants in MHS beneficiaries with B-cell NHL (Cohorts 1-3).

    Time frame: 3 years

  3. Aim 3: Create a comprehensive database and biorepository of ADSMs and other MHS beneficiaries with B-cell NHL.

    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).

    Time frame: 3 years

Secondary outcomes

  1. Exploratory Endpoints

    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.

    Time frame: 3 years

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Study locations

1 of 3 sites recruiting
08

References and documents

Publications

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  • Gonsalves SG, Ng D, Johnston JJ, Teer JK, Stenson PD, Cooper DN, Mullikin JC, Biesecker LG; NISC Comparative Sequencing Program. Using exome data to identify malignant hyperthermia susceptibility mutations. Anesthesiology. 2013 Nov;119(5):1043-53. doi: 10.1097/ALN.0b013e3182a8a8e7. PubMed 24195946 ↗
  • Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, Mullikin JC, Biesecker LG. Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Am J Hum Genet. 2012 Jul 13;91(1):97-108. doi: 10.1016/j.ajhg.2012.05.021. Epub 2012 Jun 14. PubMed 22703879 ↗
  • Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program. Interpreting secondary cardiac disease variants in an exome cohort. Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16. PubMed 23861362 ↗
  • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5. PubMed 25741868 ↗
  • Miller DT, Lee K, Abul-Husn NS, Amendola LM, Brothers K, Chung WK, Gollob MH, Gordon AS, Harrison SM, Hershberger RE, Klein TE, Richards CS, Stewart DR, Martin CL; ACMG Secondary Findings Working Group. Electronic address: documents@acmg.net. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023 Aug;25(8):100866. doi: 10.1016/j.gim.2023.100866. Epub 2023 Jun 22. PubMed 37347242 ↗
  • Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, Klein C, Morio T, Oksenhendler E, Picard C, Puel A, Puck J, Seppanen MRJ, Somech R, Su HC, Sullivan KE, Torgerson TR, Meyts I. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022 Oct;42(7):1473-1507. doi: 10.1007/s10875-022-01289-3. Epub 2022 Jun 24. PubMed 35748970 ↗
  • Bohers E, Viailly PJ, Dubois S, Bertrand P, Maingonnat C, Mareschal S, Ruminy P, Picquenot JM, Bastard C, Desmots F, Fest T, Leroy K, Tilly H, Jardin F. Somatic mutations of cell-free circulating DNA detected by next-generation sequencing reflect the genetic changes in both germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphomas at the time of diagnosis. Haematologica. 2015 Jul;100(7):e280-4. doi: 10.3324/haematol.2015.123612. Epub 2015 Mar 6. No abstract available. PubMed 25749829 ↗
  • DeRoin L, Cavalcante de Andrade Silva M, Petras K, Arndt K, Phillips N, Wanjari P, Subramanian HP, Montes D, McElherne J, Theissen M, Briese R, Das S, Godley LA, Segal J, Del Gaudio D, Fitzpatrick C, Churpek JE. Feasibility and limitations of cultured skin fibroblasts for germline genetic testing in hematologic disorders. Hum Mutat. 2022 Jul;43(7):950-962. doi: 10.1002/humu.24374. Epub 2022 Apr 14. PubMed 35419889 ↗
  • Kiaee F, Azizi G, Rafiemanesh H, Zainaldain H, Sadaat Rizvi F, Alizadeh M, Jamee M, Mohammadi S, Habibi S, Sharifi L, Jadidi-Niaragh F, Haghi S, Yazdani R, Abolhassani H, Aghamohammadi A. Malignancy in common variable immunodeficiency: a systematic review and meta-analysis. Expert Rev Clin Immunol. 2019 Oct;15(10):1105-1113. doi: 10.1080/1744666X.2019.1658523. Epub 2019 Sep 15. PubMed 31452405 ↗
  • Minard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children's Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med. 2020 Jun 4;382(23):2207-2219. doi: 10.1056/NEJMoa1915315. PubMed 32492302 ↗
  • Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk. 2013 Apr;13(2):106-11. doi: 10.1016/j.clml.2012.11.011. Epub 2012 Dec 29. PubMed 23276889 ↗
  • Barmettler S, Ong MS, Farmer JR, Choi H, Walter J. Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia. JAMA Netw Open. 2018 Nov 2;1(7):e184169. doi: 10.1001/jamanetworkopen.2018.4169. PubMed 30646343 ↗
  • Bomken S, van der Werff Ten Bosch J, Attarbaschi A, Bacon CM, Borkhardt A, Boztug K, Fischer U, Hauck F, Kuiper RP, Lammens T, Loeffen J, Neven B, Pan-Hammarstrom Q, Quinti I, Seidel MG, Warnatz K, Wehr C, Lankester AC, Gennery AR. Current Understanding and Future Research Priorities in Malignancy Associated With Inborn Errors of Immunity and DNA Repair Disorders: The Perspective of an Interdisciplinary Working Group. Front Immunol. 2018 Dec 12;9:2912. doi: 10.3389/fimmu.2018.02912. eCollection 2018. PubMed 30619276 ↗
  • Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, Bhagat G, Borges AM, Boyer D, Calaminici M, Chadburn A, Chan JKC, Cheuk W, Chng WJ, Choi JK, Chuang SS, Coupland SE, Czader M, Dave SS, de Jong D, Du MQ, Elenitoba-Johnson KS, Ferry J, Geyer J, Gratzinger D, Guitart J, Gujral S, Harris M, Harrison CJ, Hartmann S, Hochhaus A, Jansen PM, Karube K, Kempf W, Khoury J, Kimura H, Klapper W, Kovach AE, Kumar S, Lazar AJ, Lazzi S, Leoncini L, Leung N, Leventaki V, Li XQ, Lim MS, Liu WP, Louissaint A Jr, Marcogliese A, Medeiros LJ, Michal M, Miranda RN, Mitteldorf C, Montes-Moreno S, Morice W, Nardi V, Naresh KN, Natkunam Y, Ng SB, Oschlies I, Ott G, Parrens M, Pulitzer M, Rajkumar SV, Rawstron AC, Rech K, Rosenwald A, Said J, Sarkozy C, Sayed S, Saygin C, Schuh A, Sewell W, Siebert R, Sohani AR, Tooze R, Traverse-Glehen A, Vega F, Vergier B, Wechalekar AD, Wood B, Xerri L, Xiao W. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022 Jul;36(7):1720-1748. doi: 10.1038/s41375-022-01620-2. Epub 2022 Jun 22. PubMed 35732829 ↗
  • Verhoeven D, Stoppelenburg AJ, Meyer-Wentrup F, Boes M. Increased risk of hematologic malignancies in primary immunodeficiency disorders: opportunities for immunotherapy. Clin Immunol. 2018 May;190:22-31. doi: 10.1016/j.clim.2018.02.007. Epub 2018 Feb 27. PubMed 29499421 ↗
  • Lincoln SE, Nussbaum RL, Kurian AW, Nielsen SM, Das K, Michalski S, Yang S, Ngo N, Blanco A, Esplin ED. Yield and Utility of Germline Testing Following Tumor Sequencing in Patients With Cancer. JAMA Netw Open. 2020 Oct 1;3(10):e2019452. doi: 10.1001/jamanetworkopen.2020.19452. PubMed 33026450 ↗
  • Wagener R, Taeubner J, Walter C, Yasin L, Alzoubi D, Bartenhagen C, Attarbaschi A, Classen CF, Kontny U, Hauer J, Fischer U, Dugas M, Kuhlen M, Borkhardt A, Brozou T. Comprehensive germline-genomic and clinical profiling in 160 unselected children and adolescents with cancer. Eur J Hum Genet. 2021 Aug;29(8):1301-1311. doi: 10.1038/s41431-021-00878-x. Epub 2021 Apr 12. PubMed 33840814 ↗
  • Perkins AT, Haslem D, Goldsberry J, Shortt K, Sittig L, Raghunath S, Giauque C, Snow S, Fulde G, Moulton B, Jones D, Nadauld L. Universal Germline Testing of Unselected Cancer Patients Detects Pathogenic Variants Missed by Standard Guidelines without Increasing Healthcare Costs. Cancers (Basel). 2021 Nov 10;13(22):5612. doi: 10.3390/cancers13225612. PubMed 34830767 ↗
  • Landgren O, Kristinsson SY, Goldin LR, Caporaso NE, Blimark C, Mellqvist UH, Wahlin A, Bjorkholm M, Turesson I. Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. Blood. 2009 Jul 23;114(4):791-5. doi: 10.1182/blood-2008-12-191676. Epub 2009 Jan 30. PubMed 19182202 ↗
  • Ancira G, Romain J, Pham K, Thornton JA, DeStefano CB. Survival of U.S. Military Service Members With Lymphoma. Mil Med. 2023 Nov 3;188(11-12):e3407-e3410. doi: 10.1093/milmed/usad199. PubMed 37256781 ↗

Individual participant data

Plan to share: Yes — 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.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07652580
Lead sponsor
Henry M. Jackson Foundation for the Advancement of Military Medicine
Collaborators
Uniformed Services University of the Health Sciences, Murtha Cancer Center, Walter Reed National Military Medical Center, United States Naval Medical Center, Portsmouth, Children's Hospital Medical Center, Cincinnati, The American Genome Center
Responsible party
Sponsor
First posted
Jun 17, 2026
Start date
May 1, 2025
Primary completion
May 1, 2028 (estimated)
Completion
May 1, 2028 (estimated)
Last update
Sep 3, 2026

Study contacts

Christin B. Destefano, MD, Lt Col, MC, USAF
Contact
christin.destefano@usuhs.edu
(301) 295-3190
W. Grant Day, MD, LCDR, MC, USN
Contact
william.g.day26.mil@health.mil
(757) 953-2194
Christin Destefano
principal investigator · Uniformed Services University of the Health Sciences

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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