Evaluation of secondary hemophagocytic lymphohistiocytosis and its immune mechanisms

Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study

This study is trying to understand the immune system's role in secondary hemophagocytic lymphohistiocytosis by looking closely at patients' health and blood over a year to find better treatment options.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 2 sites (Bethesda, Maryland and 1 other locations)
• Trial ID: NCT06339177 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the immunopathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH) by conducting detailed clinical evaluations and immunologic assessments over a period of 9 to 12 months. Participants aged 18 and older with a confirmed diagnosis of sHLH will undergo multiple clinical evaluations and blood draws to analyze biomarkers, cellular phenotypes, and gene expression. The study seeks to identify the underlying mechanisms of sHLH and potential pathways for targeted therapies. Data will be collected longitudinally, with options for remote participation and local blood processing.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 years and older who have a confirmed diagnosis of secondary hemophagocytic lymphohistiocytosis.

Not a fit: Patients with primary hemophagocytic lymphohistiocytosis or those under 18 years of age may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and treatment options for patients with secondary hemophagocytic lymphohistiocytosis.

How similar studies have performed: While there have been studies on hemophagocytic lymphohistiocytosis, this specific approach focusing on the immunopathogenesis of secondary forms is relatively novel.

Eligibility criteria

* 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 this trial is running

Bethesda, Maryland and 1 other locations

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
• University of Pittsburgh — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Joseph M Rocco, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Joseph M Rocco, M.D.

Conditions Lymphohistiocytosis, Hemophagocytic; Secondary Hemophagocytic Lymphohistiocytosis; Macrophage Activation Syndrome; Hyperinflammatory Syndromes; Hemophagocytic Lymphohistiocytosis; HLH; MAS; Cytokine Storm Syndrome