NCT06339177 · National Institute of Allergy and Infectious Diseases (NIAID)
Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
What this study is about
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.
View original scientific description
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. ...
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
Where
- Bethesda, Maryland
- Pittsburgh, Pennsylvania
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 20, 2026 · Source of record for eligibility and locations