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

Macrophage Activation Syndrome Clinical Trial

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

Status Recruiting

Clinical Trial 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....

Clinical Trial Description

Study Description:

The purpose of this 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. ;

Related Conditions & MeSH terms

• Lymphohistiocytosis, Hemophagocytic
• Macrophage Activation Syndrome
• Syndrome

• NCT number: NCT06339177
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Joseph M Rocco, M.D.
• Phone: (301) 312-2858
• Email: joseph.rocco@nih.gov
• Status: Recruiting
• Start date: June 26, 2024
• Completion date: April 1, 2031