ClinicalTrials.gov record NCT06339177
Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This prospective observational study follows adults (18–120 years) with secondary HLH (sHLH) to learn about immune and genetic features of the condition. Participants have at least three clinical evaluations over 9–12 months (inpatient or outpatient as needed), with a physical exam and blood draw at each visit; blood collection may be done locally and shipped for research. No new treatments are given by the study, though standard care and treatment decisions remain separate from the research.
What it is studying. The study is testing which immune cells, biomarkers, and gene-expression patterns are involved in sHLH across different causes, to define mechanisms that could guide future research.
What the researchers hope to learn. To define the immunologic mechanisms of sHLH, identify biomarkers and cellular phenotypes, compare immune profiles across sHLH subgroups (malignancy, autoimmune, immune-therapy, infection, unknown), discover novel immunologic subsets using multi-omic analyses, and evaluate rare genetic variants that may influence susceptibility. (Genetic-variant testing is optional and requires separately co-enrolling in a NIAID sequencing protocol.)
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by disrupted immune function. People with HLH are prone to fevers and illnesses, which can be fatal. Some people develop a genetic form of this disease (pHLH), but researchers do not understand why some other people develop a nongenetic form (sHLH). They also do not have good ways to diagnose and treat sHLH. Objective: To learn about sHLH and why some people get it and others do not. Eligibility: Adults aged 18 years and older with sHLH. Design: Participants will be admitted to the study based on a review of their medical records. Those who join will have at least 3 clinical evaluations over 9 to 12 months. These may occur during an inpatient hospitalization if they require medical care or in the outpatient clinic. Participants will also have a physical exam at each visit. Up to half a cup of blood will be drawn at each visit. Participants may also have their blood drawn by their own doctors, who will send the samples to the researchers. Researchers may also contact these participants by telephone or video calls. The blood will be used for clinical tests as well as research. No new treatments will be administered as part of this study; however, standard medications and treatments may be recommended. Participants may opt to continue their visits once a year for 3 more years. Participants may also opt for an extra clinial evaluation 1 week after starting a new treatment. ...
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Aged 18 years or older.
- Established diagnosis of sHLH defined by meeting any published criteria, per Table 1:
- Meeting the HLH-2004 criteria.
- HScore of >168. For those without a bone marrow biopsy to evaluate for hemophagocytosis (worth 35 points in the criteria), HScore>134 will be used.
- For those with underlying rheumatologic disease: meeting the 2016 American College of Rheumatology criteria for macrophage activation syndrome.
- Agree to storage and sharing of study data and biospecimens for future research use.
- Table 1: Published Criteria for HLH
- HLH-2004 Criteria:
- Molecular diagnosis of HLH OR At least 5 of 8 below criteria:
- Fever (>38.4 Degrees Celcius)
- Splenomegaly
- Cytopenias affecting >=2 of 3 lineages: Hgb <9 g/dL, platelets <10\^5/microliter, neutrophils <10\^6/microliter
- Hypertriglyceridemia (>256 mg/dL) and/or fibrinogen <1.5 g/L
- Hemophagocytosis on biopsy
- Serum ferritin >=500 ng/mL
- Increased serum sCD25 (>2400 U/mL)
- Low or absent NK cell activity
- HScore:
- Known immunosuppression:
- 0 (no) or 18 (yes)
- Temperature (degrees, Celsius):
- 0 (<38.4), 33 (38.4-39.4), 49 (>39.4)
- Organomegaly:
- 0 (no), 23 (liver/spleen), 38 (both)
- Number of cytopenias:
- 0 (1 lines), 24 (2 lines), 34 (3 lines)
- Ferritin (ng/mL):
- 0 (<2000), 35 (2000-6000), 50 (>6000)
- Triglycerides (mg/dL):
- 0 (<1.5), 44 (1.5-4), 66 (>4)
- Fibrinogen (g/L):
- 0 (>2.5), 30 (<2.5)
- AST (IU/mL):
- 0 (<30), 19 (>30)
- Hemophagocytosis:
- 0 (no) or 35 (yes)
- Cutoff value=169
- ACR 2016-MAS Criteria:
- A febrile patient with known or suspected sJIA is classified as having macrophage activation syndrome if the following criteria are met:
- Ferritin >684 ng/mL
- AND any 2 of the following:
- Platelets <=181,000/microliter
- AST >48 IU/mL
- Triglycerides >156 mg/dL
- Fibrinogen <=3.6 g/L
- Abbreviations: ACR, American College of Rheumatology; AST, aspartate transaminase; Hgb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; MAS, macrophage activation syndrome; NK, natural killer, sJIA, systemic juvenile idiopathic arthritis.
Exclusion criteria
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Currently pregnant.
- Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
Study Description: The purpose of this multisite natural history study is to study the immunopathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH). This will include detailed longitudinal clinical and immunologic characterization of sHLH, as well as mechanistic studies evaluating inflammasome activation, cytotoxicity, and JAK-STAT signaling. Participants with sHLH will undergo clinical assessment and management along with three research blood draws with the option for additional blood draws at time points such as post-immunosuppressive treatment or treatment escalation and during longer-term follow-up. Participation may be in person or remote, with blood collected and processed locally then shipped to the NIH. Longitudinal clinical information will be recorded, and standard of care will be offered as needed. Primary Objective: To study the immunopathogenesis of sHLH from various etiologies including biomarkers, cellular phenotypes, and gene expression to determine mechanistic pathways that may be amenable to host-directed therapies. Secondary Objectives:
- To prospectively and longitudinally characterize the predisposing conditions, clinical features, acute triggers, clinical labs, and outcomes of a cohort of individuals meeting sHLH criteria.
- To compare biomarkers and immune profiles between the classically defined sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology).
- To evaluate for novel immunologic subsets of sHLH with unsupervised analyses using a multi-omic approach, including single-cell transcriptomics and proteomics.
- To evaluate for rare, protein-altering variants in genes associated with cytotoxicity, inflammasome activation, or immunoregulation via (optional) co-enrollment in NIAID Centralized Sequencing protocol.
Primary Endpoint: Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions. Secondary Endpoints:
- Characterize the longitudinal clinical course of sHLH, including relapse rates and predictors of key clinical outcomes at one year after diagnosis.
- Identify differences in clinical and/or immunologic profiles between sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology).
- To evaluate for novel immunologic profiles in sHLH using multi-omic unsupervised analyses.
- Identify new genetic determinants of susceptibility to sHLH in the setting of different predisposing conditions.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Enrollment is based on medical-record review. Participants have at least three clinical evaluations over about 9–12 months (inpatient or outpatient as needed), with a physical exam at each visit. At each visit up to about half a cup of blood is drawn for clinical tests and research; additional blood draws may occur after starting new treatments or during long-term follow-up, and participants may opt for yearly visits for three extra years. Some visits or contacts may be by phone/video and blood can be collected locally and shipped to the study team; no experimental treatments are given by the study (standard care may be recommended).
How the study is structured. A prospective observational cohort (natural history) study. Participants complete at least three visits over 9–12 months with physical exams and research blood draws (about up to half a cup each visit). Visits can occur during hospitalization or in clinic; some participation may be remote with local blood collection and shipment. Optional longer-term yearly follow-up for up to three more years and extra blood draws after starting a new treatment are available.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on hemophagocytic lymphohistiocytosis
This trial is also listed on this site under adult-onset Still's disease.
Important dates
- Study start
- Jul 2, 2024
- Primary completion
- Oct 1, 2030 (estimated)
- Study completion
- Apr 1, 2031 (estimated)
- Target enrollment
- 300 participants (estimated)
- Last updated on registry
- Sep 10, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Joseph M Rocco, M.D. 📞 (301) 312-2858 ✉ joseph.rocco@nih.gov
Participating sites (2)
- National Institutes of Health Clinical CenterRecruiting
Bethesda, Maryland, 20892 · United States
- NIH Clinical Center Office of Patient Recruitment (OPR) · 800-411-1222 ext. TTY dial 711 · ccopr@nih.gov
- University of PittsburghRecruiting
Pittsburgh, Pennsylvania, 15261 · United States
- Daniella Schwartz, M.D. · 301-761-5420 · daniella.schwartz@nih.gov
Terms used on this page · explanations by MedicalUpdates.ai
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- biospecimens
- A collection of biological samples, such as blood or tissue, stored with medical information so that researchers can study them later.
- INCLUSION CRITERIA
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- EXCLUSION CRITERIA
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- natural history study
- A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
- immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- standard of care
- Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
- Primary Objective
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- biomarkers
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
- cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Endpoints
- Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.
- relapse
- A condition that improved with treatment and has since returned or worsened.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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