Recruiting

Observational Study

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Code:

NCT06339177

Conditions

Lymphohistiocytosis, Hemophagocytic

Secondary Hemophagocytic Lymphohistiocytosis

Macrophage Activation Syndrome

Hyperinflammatory Syndromes

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Study Details

Brief summary:

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.

...

Conditions

Lymphohistiocytosis, Hemophagocytic

Secondary Hemophagocytic Lymphohistiocytosis

Macrophage Activation Syndrome

Hyperinflammatory Syndromes

Study ID

NCT06339177

Start date

Jul 2, 2024

Status verified date

Mar 18, 2026

Completion date

Apr 1, 2031

Anticipated

Primary completion date

Oct 1, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • 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 Design

Enrollment

300 participants

Anticipated

Interventions and Outcome Measures

Arms

sHLH

Hemophagocytic lymphohistiocytosis (HLH) represents a clinical condition of persistent, dysregulated immune activation with unrelenting fevers, hyperferritinemia, and cytopenias, which lead to multiorgan failure and death.

Primary outcome measure

  • Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions. [ Time Frame: Through end of study. ]

Central Contacts and Locations

Central contacts

Joseph M Rocco, M.D.

(301) 312-2858joseph.rocco@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

NIH Clinical Center Office of Patient Recruitment (OPR)

800-411-1222ccopr@nih.gov

University of Pittsburgh

Recruiting

Pittsburgh, Pennsylvania, United States, 15261

Contacts

Daniella Schwartz, M.D.

301-761-5420daniella.schwartz@nih.gov

More Information

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Last update posted

Mar 20, 2026

Last verified

Mar 18, 2026

Keywords

  • Hemophagocytic Lymphohistiocytosis
  • HLH
  • Macrophage Activation Syndrome
  • MAS
  • Cytokine Storm Syndrome
  • Hyperinflammatory Syndrome
  • Hyperinflammation
  • Still's Disease
  • Hyperferritinemia
  • Immune Dysregulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Institute of Allergy and Infectious Diseases (NIAID) on 2026-03-20.