INTO-HLH: A Disease Registry for Patients With Hemophagocytic Lymphohistiocytosis (HLH)

Hemophagocytic Lymphohistiocytoses Clinical Trial

Official title:

INTO-HLH- Insight Into the Natural History and Treatment Outcomes of Hemophagocytic Lymphohistiocytosis (HLH): A Disease Registry for Patients With HLH

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05277272
• Other study ID #: 2021-0821
• Secondary ID: Sobi.HLH-RWE102
• Status: Recruiting
• Start date: December 31, 2021
• Est. completion date: January 2026

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Michael Jordan, MD
• Phone: (513) 803-9063
• Email: Michael.Jordan[@]cchmc.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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:

• None

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytoses
• Lymphohistiocytosis, Hemophagocytic

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Baylor College of Medicine, Sobi, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to HLH diagnosis from the initial presentation	Date of initial presentation and the date of HLH diagnosis as defined by HLH diagnostic criteria (HLH-2004/MAS classification criteria)	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.
Primary	Number of patients with an autoimmune disease at the time of HLH diagnosis	Presence of an autoimmune disease at the time of diagnosis (e.g., Systemic juvenile idiopathic arthritis, lupus)	Up to 1 month from HLH diagnosis
Primary	Number of patients with malignancy at the time of HLH diagnosis	Presence of hematologic and solid malignancies at the time of HLH diagnosis.	Up to 1 month from HLH diagnosis.
Primary	Number of patients treated with immune-activating agents before HLH diagnosis	The number of patients treated with immune-activating agents before initial diagnosis (checkpoint inhibitors, CAR-T constructs)	Up to 1 month before HLH diagnosis.
Primary	Number of patients with central nervous system (CNS) involvement during the HLH disease course.	CNS involvement as defined by elevated neopterin, white blood cells, or protein at a cerebrospinal fluid or changes in MRI	Up to 1 month from HLH diagnosis.
Primary	Frequency of a genetic diagnosis underlying the HLH.	Data on genetic testing will be gathered and investigators will summarize the number to calculate the frequency of a genetic diagnosis.	Up to 1 month from HLH diagnosis.
Primary	Number of patients with infections (e.g., EBV, CMV, HHV6, HIV, fungal, bacterial) at the time of diagnosis.	The presence of infections at HLH diagnosis (serology and polymerase chain reaction).	Up to 1 month from HLH diagnosis.
Primary	Number of patients with organ failure.	Data will be gathered on organ failure related to HLH (e.g., kidney, lung, CNS).	Up to 1 year from HLH diagnosis.
Primary	Number of patients with long-term disease-related complications.	Data on long-term complications (e.g., impaired growth, impaired cognitive development) will be gathered.	Up to 5 years from HLH diagnosis.
Secondary	Treatment response rate to HLH-related treatments.	The response of all treatments for all patients using the criteria used to assess the efficacy of anti-IFN treatment in the NI-0501-04 04 and NI-0501-14 clinical trials.	Week two from the start of treatment.
Secondary	Time to response to HLH-related therapy for patients in the registry.	The response of all treatments for all patients using the criteria used to assess the efficacy of anti-IFN treatment in the NI-0501-04 04 and NI-0501-14 clinical trials.	Assessed up to 12 weeks from start of treatment.
Secondary	The survival probability of patients in the registry	Data on the occurrence and date of death and the date of last documentation for living patients will be gathered.	From HLH diagnosis to last follow-up or death, whichever comes first, assessed up to 5 years post-HLH diagnosis.
Secondary	Number of patients who received hematopoietic stem cell transplantation (HSCT)	Data on the frequency of HSCT will be gathered.	From HLH diagnoses up to 5 years post-HLH diagnosis.
Secondary	Frequency of hematopoietic stem cell transplantation (HSCT) related complications	Investigators will gather data on the frequency of primary graft failure and reception of more than one cellular product, secondary graft failure, and chimerism post-HSCT. Primary graft failure is defined as the observed record of failure to achieve an absolute neutrophil count (ANC) of >500/µL by 42 days after HSCT. Secondary graft failure is defined as the observed record of cytopenia after initial engraftment (ANC <500/ µL) and is not related to infection or drug toxicity, loss of donor chimerism <5%. Mixed chimerism is defined as <80% donor cells after day +30.	From HSCT up to 5 years post HSCT.
Secondary	Number of participants with treatment-related adverse events >/= 3 as assessed by CTCAE 5.0	Grade 3 and higher adverse events (per CTCAE 5.0) reported in the medical charts will be collected. The data will be summarized and described using descriptive statistics.	From initiation of HLH related treatment up to 30 days following discontinuation of treatment.