Evaluation of IFNγ and Inflammatory Mediators in Patients With Hemophagocytic Lymphohistiocytosis

An Observational, Multicenter Study to Evaluate Levels of Interferon Gamma (IFNγ) and Other Inflammatory Mediators in Adult Patients With Hemophagocytic Lymphohistiocytosis (A-HLH)

This observational study is designed to provide a better understanding of the potential use of interferon gamma (IFNγ) and IFNγ-inducible chemokines as markers of HLH disease activity in adults, and the potential of IFNγ to represent a therapeutic target.

Study Overview

• Status: Completed
• Conditions: Hemophagocytic Lymphohistiocytoses
• Intervention / Treatment: Other: Blood Draws Data Collection

Detailed Description

This is a observational study designed to determine the levels of pro-inflammatory markers in adult patients diagnosed with HLH and to assess the relationship between the biomarkers and disease activity in these patients during the HLH course. Inflammatory markers include IFNγ and IFNγ-induced chemokines C-X-C chemokine ligand 9 and C-X-C chemokine ligand 10.

In addition to the blood samples for the biomarker analysis, relevant information gathered by the treating physician will be collected in a data collection form. Whenever possible, collection of serum samples for biomarker analysis and relevant information should occur at HLH diagnosis, at regular time intervals during the treatment course (not more than once a week) up to resolution of HLH.

Blood samples will also be sent to the study sponsor (NovImmune S.A.) for cytokine testing. Before patient's samples are sent to the sponsor for testing, patient's name and any personal identifying information will be coded to protect participant's privacy.

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Male and female adult (>=18 years old) patients who are diagnosed with HLH and meet the inclusion criteria.

Description

Inclusion Criteria:

• Patients >=18 years old diagnosed with active HLH as established by the treating physician.
• HLH forms of unknown origin or secondary to infections or rheumatologic disorders.
• Should the diagnosis of primary HLH or malignancy become apparent after inclusion, the data collected will be analyzed separately as additional cohorts.
• The patient must have consented to the use of their clinical data for research purposes at the site.

Exclusion Criteria:

• Patients with primary HLH (diagnosed by the presence of homozygous mutations in a known HLH causative gene) and secondary HLH due to malignancy are excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
A-HLH Patients; Patients diagnosed with A-HLH.	Other: Blood Draws Data Collection
Malignancy-Associated Hemophagocytic Lymphohistiocytosis (M-HLH) Patients; Patients diagnosed with HLH in the context of a malignancy.	Other: Blood Draws Data Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Serum Concentration of Inflammatory Biomarker - C-X-C Chemokine Ligand 10 (CXCL10)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of CXCL10.	11 months
Mean Serum Concentration of Inflammatory Biomarker - C-X-C Chemokine Ligand 9 (CXCL9)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of CXCL9.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Interferon Gamma (IFNg)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of IFNg.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Interleukin 10 (IL-10)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of IL-10.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Interleukin 1 Beta (IL-1B)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of IL-1B.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Interleukin 6 (IL-6)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of IL-6.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Neopterin	Serum samples was collected at various times after HLH diagnosis to determine the concentration of neopterin.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Tumor Necrosis Factor Alpha (TNFa)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of TNFa.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Total Human Interferon Gamma (hIFNg)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of hIFNg.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Soluble CD163 (sCD163)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of sCD163.	11 months
Mean Serum Concentration of Inflammatory Biomarker - Soluble IL-2 Receptor Alpha (sIL2Ra)	Serum samples was collected at various times after HLH diagnosis to determine the concentration of sIL2Ra.	11 months
Mean Serum Concentration of White Blood Cells	Blood samples was collected at various times after HLH diagnosis to determine the concentration of white blood cells.	11 months
Mean Serum Concentration of Red Blood Cells	Blood samples was collected at various times after HLH diagnosis to determine the concentration of red blood cells.	11 months
Mean Serum Concentration of Hemoglobin	Blood samples was collected at various times after HLH diagnosis to determine the concentration of hemoglobin.	11 months
Mean Serum Concentration of Hematocrit	Blood samples was collected at various times after HLH diagnosis to determine the concentration of hematocrit.	11 months
Mean Serum Concentration of Platelets	Blood samples was collected at various times after HLH diagnosis to determine the concentration of platelets.	11 months
Mean Serum Concentration of Neutrophils	Blood samples was collected at various times after HLH diagnosis to determine the concentration of neutrophils.	11 months
Mean Serum Concentration of Lymphocytes	Blood samples was collected at various times after HLH diagnosis to determine the concentration of lymphocytes.	11 months
Mean Serum Concentration of Monocytes	Blood samples was collected at various times after HLH diagnosis to determine the concentration of monocytes.	11 months
Mean Serum Concentration of Eosinophils	Blood samples was collected at various times after HLH diagnosis to determine the concentration of eosinophils.	11 months
Mean Serum Concentration of Basophils	Blood samples was collected at various times after HLH diagnosis to determine the concentration of basophils.	11 months
Mean Plasma Concentration of D-Dimer	Blood samples was collected at various times after HLH diagnosis to determine the concentration of D-dimer.	11 months
Mean Plasma Concentration of Fibrinogen	Blood samples was collected at various times after HLH diagnosis to determine the concentration of fibrinogen.	11 months
Mean Activated Partial Thromboplastin Time (aPTT)	Blood samples was collected at various times after HLH diagnosis to determine the aPTT.	11 months
Mean Prothrombin Time	Blood samples was collected at various times after HLH diagnosis to determine the prothrombin time.	11 months
Mean Serum Concentration of C-Reactive Protein	Blood samples was collected at various times after HLH diagnosis to determine the concentration of c-reactive protein.	11 months
Mean Serum Concentration of Ferritin	Blood samples was collected at various times after HLH diagnosis to determine the concentration of ferritin.	11 months
Mean Plasma Concentration of Blood Urea Nitrogen	Blood samples was collected at various times after HLH diagnosis to determine the concentration of blood urea nitrogen.	11 months
Mean Serum Concentration of Creatinine	Blood samples was collected at various times after HLH diagnosis to determine the concentration of creatinine.	11 months
Mean Serum Concentration of Albumin	Blood samples was collected at various times after HLH diagnosis to determine the concentration of albumin.	11 months
Mean Serum Concentration of Sodium	Blood samples was collected at various times after HLH diagnosis to determine the concentration of sodium.	11 months
Mean Serum Concentration of Fasting Triglycerides	Blood samples was collected at various times after HLH diagnosis to determine the concentration of fasting triglycerides.	11 months
Mean Serum Concentration of Total Bilirubin	Blood samples was collected at various times after HLH diagnosis to determine the concentration of total bilirubin.	11 months
Mean Serum Concentration of Conjugated Bilirubin	Blood samples was collected at various times after HLH diagnosis to determine the concentration of conjugated bilirubin.	11 months
Mean Serum Concentration of Alanine Aminotransferase	Blood samples was collected at various times after HLH diagnosis to determine the concentration of alanine aminotransferase.	11 months
Mean Serum Concentration of Aspartate Aminotransferase	Blood samples was collected at various times after HLH diagnosis to determine the concentration of aspartate aminotransferase.	11 months
Mean Serum Concentration of Alkaline Phosphatase	Blood samples was collected at various times after HLH diagnosis to determine the concentration of alkaline phosphatase.	11 months
Mean Serum Concentration of Lactate Dehydrogenase	Blood samples was collected at various times after HLH diagnosis to determine the concentration of lactate dehydrogenase.	11 months
Mean Serum Concentration of Immunoglobulin G (IgG)	Blood samples was collected at various times after HLH diagnosis to determine the concentration of IgG.	11 months

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: Harvard Medical School (HMS and HSDM); Brigham and Women's Hospital
• Investigators: Principal Investigator: Nancy Berliner, MD, Brigham and Women's Hospital

Publications and helpful links

Helpful Links

• Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2016
• Primary Completion (Actual): October 30, 2019
• Study Completion (Actual): October 30, 2019

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers; Inflammatory Markers; Interferon Gamma; IFNγ; Hemophagocytic Lymphohistiocytosis
• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: NI-0501-08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No