Hemophagocytic LymphohistiocytosesNCT05277272
INTO-HLH: A Disease Registry for Patients With Hemophagocytic Lymphohistiocytosis (HLH)
An observational study of Hemophagocytic Lymphohistiocytoses, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hemophagocytic Lymphohistiocytoses
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2021to Jan 2027
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with clinically suspected or confirmed HLH
Who may be able to join
- 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)
Who cannot join
- None
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Adi Zoref Lorenz, MD contact
United States1 site, 1 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Michael Jordan, MD, 513-803-9063, Michael.Jordan@cchmc.org
Michael Jordan, MD
About this study
Official title: INTO-HLH- Insight Into the Natural History and Treatment Outcomes of Hemophagocytic Lymphohistiocytosis (HLH): A Disease Registry for Patients With HLH
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.
Read the 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.
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis | Multi-institutional cohort registry of patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
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)
Measured: Up to 1 month from HLH diagnosis
Number of patients with malignancy at the time of HLH diagnosis
Presence of hematologic and solid malignancies at the time of HLH diagnosis.
Measured: Up to 1 month from HLH diagnosis.
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)
Measured: Up to 1 month before HLH diagnosis.
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
Measured: Up to 1 month from HLH diagnosis.
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.
Measured: Up to 1 month from HLH diagnosis.
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).
Measured: Up to 1 month from HLH diagnosis.
Number of patients with organ failure.
Data will be gathered on organ failure related to HLH (e.g., kidney, lung, CNS).
Measured: Up to 1 year from HLH diagnosis.
Number of patients with long-term disease-related complications.
Data on long-term complications (e.g., impaired growth, impaired cognitive development) will be gathered.
Measured: Up to 5 years from HLH diagnosis.
Secondary outcomes (6)
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.
Measured: Week two from the start of treatment.
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.
Measured: Assessed up to 12 weeks from start of treatment.
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.
Measured: 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)
Data on the frequency of HSCT will be gathered.
Measured: From HLH diagnoses up to 5 years post-HLH diagnosis.
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.
Measured: From HSCT up to 5 years post HSCT.
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.
Measured: From initiation of HLH related treatment up to 30 days following discontinuation of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2022
- Study start31 Dec 2021
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophagocytic LymphohistiocytosesStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Sobi, Inc., Baylor College of Medicine
- Responsible party
- Sponsor
- Investigators
- Michael Jordan, MD, Study chair, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05277272
- Sponsor's protocol ID
- 2021-0821
- Other IDs
- Sobi.HLH-RWE102
- Status last verified
- Feb 2026
- First submitted
- 29 Dec 2021
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data that will be shared include individual participant data that underlie the results reported in the article, after de-identification. Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. The types of analyses will include research on HLH.
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- INTO-HLH- Insight Into the Natural History and Treatment Outcomes of Hemophagocytic Lymphohistiocytosis (HLH): A Disease Registry for Patients With HLH
- ClinicalTrials.gov ID
- NCT05277272
- Acronym / sponsor ID
- 2021-0821
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Sobi, Inc., Baylor College of Medicine
- Study start
- 31 Dec 2021 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 14 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis | – | –Multi-institutional cohort registry of patients with clinically suspected or confirmed Hemophagocytic Lymphohistiocytosis |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with clinically suspected or confirmed HLH
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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 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.
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).
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.
6 secondary outcomes
Treatment response rate to HLH-related treatments.
Time frame: Week two from the start of treatment.
Time to response to HLH-related therapy for patients in the registry.
Time frame: Assessed up to 12 weeks from start of treatment.
The survival probability of patients in the registry
Time frame: 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)
Time frame: From HLH diagnoses up to 5 years post-HLH diagnosis.
Frequency of hematopoietic stem cell transplantation (HSCT) related complications
Time frame: From HSCT up to 5 years post HSCT.
Number of participants with treatment-related adverse events >/= 3 as assessed by CTCAE 5.0
Time frame: From initiation of HLH related treatment up to 30 days following discontinuation of treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Individual participant dataSharing planned: Yes. Data that will be shared include individual participant data that underlie the results reported in the article, after de-identification. Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. The types of analyses will include research on HLH.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Adi Zoref Lorenz, MD contact
Michael Jordan, MD study chair
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophagocytic Lymphohistiocytoses, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Jordan, MD ((513) 803-9063, Michael.Jordan@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.