INTO-HLH- Insight Into the Natural History and Treatment Outcomes of Hemophagocytic Lymphohistiocytosis (HLH): A Disease Registry for Patients With HLH
Overview
- Phase
- Not Applicable
- Intervention
- Patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Sponsor
- Children's Hospital Medical Center, Cincinnati
- Enrollment
- 200
- Locations
- 2
- Primary Endpoint
- Number of patients with infections (e.g., EBV, CMV, HHV6, HIV, fungal, bacterial) at the time of diagnosis.
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
The purpose of this observational study is to collect data on the natural history of disease of patients with Hemophagocytic Lymphohistiocytosis (HLH) including diagnosis, treatments, responses, and outcomes.
Detailed Description
Hemophagocytic Lymphohistiocytosis (HLH) is a complex, hyperinflammatory syndrome resulting from the interplay of genetic predisposition and various environmental factors. Despite available treatment options for HLH, approximately 30% of patients do not respond to therapy. Moreover, the standard therapy is constrained by its toxicities, and safer treatments are pursued. There is an unmet need for a deeper understanding of the natural history, clinical/etiologic diversity, complications, and treatment outcomes of patients with HLH, specifically from North America. The proposed study, a collaboration between Cincinnati Children's Hospital Medical Center (CCHMC), Texas Children's Hospital, and Sobi Inc. aims to establish a robust registry that will enable investigators to better define the natural history of HLH.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with clinically suspected or confirmed HLH, including those meeting the HLH-2004 diagnostic criteria (primary or secondary forms, including malignancy) and other forms of HLH (macrophage activation syndrome \[MAS\], cytokine release syndrome \[CRS\], etc.)
- •Signed and dated informed consent and assent (adolescents)
Exclusion Criteria
- Not provided
Arms & Interventions
Patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis
Multi-institutional cohort registry of patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis
Outcomes
Primary Outcomes
Number of patients with infections (e.g., EBV, CMV, HHV6, HIV, fungal, bacterial) at the time of diagnosis.
Time Frame: Up to 1 month from HLH diagnosis.
The presence of infections at HLH diagnosis (serology and polymerase chain reaction).
Number of patients with organ failure.
Time Frame: Up to 1 year from HLH diagnosis.
Data will be gathered on organ failure related to HLH (e.g., kidney, lung, CNS).
Time to HLH diagnosis from the initial presentation
Time Frame: Interval between date of presentation, as defined as the day of appearance of initial HLH symptom, and the date of full HLH diagnosis, as defined by fulfilling the HLH diagnostic criteria, will be measured. Timeframes up to 6 months will be assessed.
Date of initial presentation and the date of HLH diagnosis as defined by HLH diagnostic criteria (HLH-2004/MAS classification criteria)
Number of patients with an autoimmune disease at the time of HLH diagnosis
Time Frame: Up to 1 month from HLH diagnosis
Presence of an autoimmune disease at the time of diagnosis (e.g., Systemic juvenile idiopathic arthritis, lupus)
Number of patients with malignancy at the time of HLH diagnosis
Time Frame: Up to 1 month from HLH diagnosis.
Presence of hematologic and solid malignancies at the time of HLH diagnosis.
Number of patients treated with immune-activating agents before HLH diagnosis
Time Frame: Up to 1 month before HLH diagnosis.
The number of patients treated with immune-activating agents before initial diagnosis (checkpoint inhibitors, CAR-T constructs)
Number of patients with long-term disease-related complications.
Time Frame: Up to 5 years from HLH diagnosis.
Data on long-term complications (e.g., impaired growth, impaired cognitive development) will be gathered.
Number of patients with central nervous system (CNS) involvement during the HLH disease course.
Time Frame: Up to 1 month from HLH diagnosis.
CNS involvement as defined by elevated neopterin, white blood cells, or protein at a cerebrospinal fluid or changes in MRI
Frequency of a genetic diagnosis underlying the HLH.
Time Frame: Up to 1 month from HLH diagnosis.
Data on genetic testing will be gathered and investigators will summarize the number to calculate the frequency of a genetic diagnosis.
Secondary Outcomes
- Treatment response rate to HLH-related treatments.(Week two from the start of treatment.)
- Frequency of hematopoietic stem cell transplantation (HSCT) related complications(From HSCT up to 5 years post HSCT.)
- Time to response to HLH-related therapy for patients in the registry.(Assessed up to 12 weeks from start of treatment.)
- The survival probability of patients in the registry(From HLH diagnosis to last follow-up or death, whichever comes first, assessed up to 5 years post-HLH diagnosis.)
- Number of patients who received hematopoietic stem cell transplantation (HSCT)(From HLH diagnoses up to 5 years post-HLH diagnosis.)
- Number of participants with treatment-related adverse events >/= 3 as assessed by CTCAE 5.0(From initiation of HLH related treatment up to 30 days following discontinuation of treatment.)