Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma (TOXNHL)
1. september 2026 oppdatert av: 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.
Studieoversikt
Status
Rekruttering
Detaljert beskrivelse
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.
Studietype
Observasjonsmessig
Registrering (Antatt)
300
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Christin B. Destefano, MD, Lt Col, MC, USAF
- Telefonnummer: (301) 295-3190
- E-post: christin.destefano@usuhs.edu
Studer Kontakt Backup
- Navn: W. Grant Day, MD, LCDR, MC, USN
- Telefonnummer: (757) 953-2194
- E-post: william.g.day26.mil@health.mil
Studiesteder
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Maryland
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Bethesda, Maryland, Forente stater, 20814
- Rekruttering
- Walter Reed National Military Medical Center
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Ta kontakt med:
- Christin B Destefano
- Telefonnummer: (301) 295-3190
- E-post: christin.destefano@usuhs.edu
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Ta kontakt med:
- Annika Hamann, RN, BSN, BS
- Telefonnummer: (301) 295-4198
- E-post: annika.hamann.ctr@usuhs.edu
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Hovedetterforsker:
- Jeremy Perkins, MD, FACP, COL, US Army (ret)
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Bethesda, Maryland, Forente stater, 20814
- Aktiv, ikke rekrutterende
- Uniformed Services University of the Health Sciences
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Virginia
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Portsmouth, Virginia, Forente stater, 23708
- Aktiv, ikke rekrutterende
- Naval Medical Center Portsmouth
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
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.
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
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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.
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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.
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Cohort 3
Other MHS beneficiaries ages 4-17 who are newly diagnosed with B-cell NHL or are untreated.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Aim 1: Characterize occupational exposures and their impact on health outcomes and immune health of ADSMs and other MHS beneficiaries with B-cell NHL.
Tidsramme: 3 years
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3 years
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Aim 2: Identify and interpret germline variants in ADSMs and other MHS beneficiaries with B-cell NHL.
Tidsramme: 3 years
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1. Determine the relative frequency of germline pathogenic/likely pathogenic variants in MHS beneficiaries with B-cell NHL (Cohorts 1-3).
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3 years
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Aim 3: Create a comprehensive database and biorepository of ADSMs and other MHS beneficiaries with B-cell NHL.
Tidsramme: 3 years
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3 years
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Exploratory Endpoints
Tidsramme: 3 years
|
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3 years
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Christin Destefano, Uniformed Services University of the Health Sciences
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, Herman GE, Hufnagel SB, Klein TE, Korf BR, McKelvey KD, Ormond KE, Richards CS, Vlangos CN, Watson M, Martin CL, Miller DT. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017 Feb;19(2):249-255. doi: 10.1038/gim.2016.190. Epub 2016 Nov 17.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
1. mai 2025
Primær fullføring (Antatt)
1. mai 2028
Studiet fullført (Antatt)
1. mai 2028
Datoer for studieregistrering
Først innsendt
11. juni 2026
Først innsendt som oppfylte QC-kriteriene
11. juni 2026
Først lagt ut (Faktiske)
17. juni 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
3. september 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
1. september 2026
Sist bekreftet
1. september 2026
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- USUHS.2024-137
- HU00012520036 (Annet stipend/finansieringsnummer: Uniformed Services University of the Health Sciences)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
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.
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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