INTO-HLH: A Disease Registry for Patients With Hemophagocytic Lymphohistiocytosis (HLH)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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, the North American Consortium for Histiocytosis (NACHO), and Sobi Inc. aims to establish a robust registry that will enable investigators to better define the natural history of HLH.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis Multi-institutional cohort registry of patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis |
Outcome Measures
Primary Outcome Measures
- Time to HLH diagnosis from the initial presentation [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 [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 [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 [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 central nervous system (CNS) involvement during the HLH disease course. [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. [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.
- Number of patients with infections (e.g., EBV, CMV, HHV6, HIV, fungal, bacterial) at the time of diagnosis. [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. [Up to 1 year from HLH diagnosis.]
Data will be gathered on organ failure related to HLH (e.g., kidney, lung, CNS).
- Number of patients with long-term disease-related complications. [Up to 5 years from HLH diagnosis.]
Data on long-term complications (e.g., impaired growth, impaired cognitive development) will be gathered.
Secondary Outcome Measures
- Treatment response rate to HLH-related treatments. [Week two from the start of treatment.]
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.
- Time to response to HLH-related therapy for patients in the registry. [Assessed up to 12 weeks from start of treatment.]
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.
- 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.]
Data on the occurrence and date of death and the date of last documentation for living patients will be gathered.
- Number of patients who received hematopoietic stem cell transplantation (HSCT) [From HLH diagnoses up to 5 years post-HLH diagnosis.]
Data on the frequency of HSCT will be gathered.
- Frequency of hematopoietic stem cell transplantation (HSCT) related complications [From HSCT up to 5 years post HSCT.]
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.
- 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.]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.)
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Signed and dated informed consent and assent (adolescents)
Exclusion Criteria:
- None
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
Sponsors and Collaborators
- Children's Hospital Medical Center, Cincinnati
- Sobi, Inc.
- North American Consortium for Histiocytosis
- Baylor College of Medicine
Investigators
- Study Chair: Michael Jordan, MD, Children's Hospital Medical Center, Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-0821
- Sobi.HLH-RWE102