Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma (TOXNHL)
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.
研究概览
详细说明
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.
研究类型
观察性的
注册 (估计的)
300
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Christin B. Destefano, MD, Lt Col, MC, USAF
- 电话号码：(301) 295-3190
- 邮箱：christin.destefano@usuhs.edu
研究联系人备份
- 姓名：W. Grant Day, MD, LCDR, MC, USN
- 电话号码：(757) 953-2194
- 邮箱：william.g.day26.mil@health.mil
学习地点
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Maryland
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Bethesda、Maryland、美国、20814
- 招聘中
- Walter Reed National Military Medical Center
-
接触：
- Christin B Destefano
- 电话号码：(301) 295-3190
- 邮箱：christin.destefano@usuhs.edu
-
接触：
- Annika Hamann, RN, BSN, BS
- 电话号码：(301) 295-4198
- 邮箱：annika.hamann.ctr@usuhs.edu
-
首席研究员：
- Jeremy Perkins, MD, FACP, COL, US Army (ret)
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Bethesda、Maryland、美国、20814
- 主动，不招人
- Uniformed Services University of the Health Sciences
-
-
Virginia
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Portsmouth、Virginia、美国、23708
- 主动，不招人
- Naval Medical Center Portsmouth
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-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
不
取样方法
非概率样本
研究人群
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.
描述
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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
|---|
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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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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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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.
大体时间：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.
大体时间：3 years
|
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.
大体时间：3 years
|
|
3 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Exploratory Endpoints
大体时间：3 years
|
|
3 years
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 首席研究员：Christin Destefano、Uniformed Services University of the Health Sciences
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
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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.
- 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.
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- 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.
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- 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.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2025年5月1日
初级完成 (估计的)
2028年5月1日
研究完成 (估计的)
2028年5月1日
研究注册日期
首次提交
2026年6月11日
首先提交符合 QC 标准的
2026年6月11日
首次发布 (实际的)
2026年6月17日
研究记录更新
最后更新发布 (实际的)
2026年9月3日
上次提交的符合 QC 标准的更新
2026年9月1日
最后验证
2026年9月1日
更多信息
与本研究相关的术语
其他研究编号
- USUHS.2024-137
- HU00012520036 (其他赠款/资助编号：Uniformed Services University of the Health Sciences)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
是的
IPD 计划说明
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.
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.