Histiocytosis, Langerhans-CellNCT04100408
Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)
An observational study of Histiocytosis, Langerhans-Cell, run by Children's Oncology Group at 1 site in United States.
Trial summary
The long-term goal is to define the mechanisms of pathogenesis underlying Langerhans cell histiocytosis (LCH). The overall objectives of the current study are to characterize the role of SMAD6 inherited genetic variation on LCH susceptibility and identify germline genomic regions associated with LCH somatic mutations. Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Histiocytosis, Langerhans-Cell
- What is being tested?
- Biospecimen Collection, Laboratory Biomarker Analysis and Questionnaire Administration
- How many people
- 647 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2020to 30 Sep 2026
- 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 Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients diagnosed with Langerhans cell histiocytosis (LCH) on or after January 1, 2008.
Who may be able to join
- ≤ 25 years old at the time of original LCH diagnosis
- The patient must be enrolled on ACCRN07 and/or APEC14B1 and registered with COG by a North American member institution
- The patient must have a diagnosis of LCH (ICD Codes/Morphology: 9751/1; 9752/1; 9753/1; or 9754/3).
- The patient must be diagnosed with LCH on or after January 1, 2008.
- All questionnaire respondents must understand English or Spanish.
- All patients and/or their parents or legal guardians must provide informed consent.
- All institutional, FDA, and NCI requirements for human studies must be met.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
About this study
The long-term goal is to define the mechanisms of pathogenesis underlying Langerhans cell histiocytosis (LCH). The overall objectives of the current study are to characterize the role of SMAD6 inherited genetic variation on LCH susceptibility and identify germline genomic regions associated with LCH somatic mutations. Building from preliminary data, the central hypotheses are: (1) causal genetic variants in SMAD6 underlie susceptibility to LCH, and (2) differences in LCH-related somatic activating mutations by race/ethnicity are related to Amerindian (i.e., Native American) genetic ancestry. The Central hypothesis will be tested by pursuing the specific aims.
Read the detailed description
PRIMARY OBJECTIVES:
- To comprehensively characterize germline variants in SMAD6 and their association with LCH.
II. To identify novel germline variants associated with LCH.
III.To determine the role of genetic ancestry on LCH-related somatic mutations.
EXPLORATORY OBJECTIVES:
- To integrate clinical and epidemiologic questionnaire data with genetic risk factor data from the Primary Aims to more comprehensively elucidate LCH susceptibility.
OUTLINE:
Case identification and recruitment followed by questionnaires and specimen processing.
- Conditions
- Histiocytosis, Langerhans-Cell
- Being tested
- Biospecimen Collection, Laboratory Biomarker Analysis, Questionnaire Administration
- Medical subject headings
- Histiocytosis, Langerhans-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionOther
Undergo saliva or buccal mucosa collection
Laboratory Biomarker AnalysisOther
Correlative studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Ancillary-Correlative (biospecimen collection) | LCH patients and their parents undergo collection of saliva or buccal mucosa samples for genetic mutational analysis. Germline DNA from saliva or buccal brushing will be sequenced, genotyped, and analyzed. Receives: Other: Biospecimen Collection; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterized germline variants in SMAD6 and their association with Langerhans Cell Histiocytosis (LCH)
Will re-sequence SMAD6 among LCH case-parent trios to characterize the association between SMAD6 inherited genetic effects and LCH susceptibility using targeted next-generation sequencing. We will also analyze de novo single-nucleotide variants (SNVs), copy-number variants (CNVs), and insertions/deletions(INDELs) obtained through SMAD6 sequence data generated from the biologic samples of the CCRN/PEC LCH case-parent trios.
Measured: Up to 4 years
The frequency of de novo mutations and systematic assessment of the underlying genetic makeup of LCH
Will use the maximum number of LCH case-parent trios enrolled utilizing the CCRN/PEC with viable biologic samples to conduct genome-wide SNP genotyping. This methodology will identify new genes and pathways associated with LCH susceptibility. We will also determine the prevalence of novel de novo mutations associated with LCH in these case-parent trios. This will provide a systematic assessment of the underlying genetic makeup of LCH in a large sample of families.
Measured: Up to 4 years
The difference in LCH-related somatic mutations by race/ethnicity due to underlying genetic ancestry
Genetic ancestry will be determined using germline genome-wide SNP array data generated from CCRN/PEC LCH cases in Aim 2. In parallel, we will determine patient somatic mutational profiles using a custom, targeted 91-gene panel. We will then conduct a genome-wide admixture-mapping scan to identify LCH-related loci that are associated with specific LCH somatic mutational profiles.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start1 Jun 2020
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Histiocytosis, Langerhans-CellStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe 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
- Family based
- Time perspective
- Prospective
- Enrolment
- 647 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Michael Scheurer, PhD, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04100408
- Sponsor's protocol ID
- AEPI17N1
- Status last verified
- Jan 2026
- First submitted
- 20 Sep 2019
- Last updated
- 9 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)
- ClinicalTrials.gov ID
- NCT04100408
- Acronym / sponsor ID
- AEPI17N1
- Conditions
- Histiocytosis, Langerhans-Cell
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 647 participants (estimated)
- Lead sponsor
- Children's Oncology GroupResearch network
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 24 Sep 2019 (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 long-term goal is to define the mechanisms of pathogenesis underlying Langerhans cell histiocytosis (LCH). The overall objectives of the current study are to characterize the role of SMAD6 inherited genetic variation on LCH susceptibility and identify germline genomic regions associated with LCH somatic mutations. Building from preliminary data, the central hypotheses are: (1) causal genetic variants in SMAD6 underlie susceptibility to LCH, and (2) differences in LCH-related somatic activating mutations by race/ethnicity are related to Amerindian (i.e., Native American) genetic ancestry. The Central hypothesis will be tested by pursuing the specific aims.
Detailed description
PRIMARY OBJECTIVES:
- To comprehensively characterize germline variants in SMAD6 and their association with LCH.
II. To identify novel germline variants associated with LCH.
III.To determine the role of genetic ancestry on LCH-related somatic mutations.
EXPLORATORY OBJECTIVES:
- To integrate clinical and epidemiologic questionnaire data with genetic risk factor data from the Primary Aims to more comprehensively elucidate LCH susceptibility.
OUTLINE:
Case identification and recruitment followed by questionnaires and specimen processing.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ancillary-Correlative (biospecimen collection) | – | Other: Biospecimen Collection, Other: Laboratory Biomarker Analysis, Other: Questionnaire AdministrationLCH patients and their parents undergo collection of saliva or buccal mucosa samples for genetic mutational analysis. Germline DNA from saliva or buccal brushing will be sequenced, genotyped, and analyzed. |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients diagnosed with Langerhans cell histiocytosis (LCH) on or after January 1, 2008.
Key inclusion criteria (7 listed)
- ≤ 25 years old at the time of original LCH diagnosis
- The patient must be enrolled on ACCRN07 and/or APEC14B1 and registered with COG by a North American member institution
- The patient must have a diagnosis of LCH (ICD Codes/Morphology: 9751/1; 9752/1; 9753/1; or 9754/3).
- The patient must be diagnosed with LCH on or after January 1, 2008.
- All questionnaire respondents must understand English or Spanish.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biospecimen CollectionUndergo saliva or buccal mucosa collection | Other | Ancillary-Correlative (biospecimen collection) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Ancillary-Correlative (biospecimen collection) |
| Questionnaire AdministrationAncillary studies | Other | Ancillary-Correlative (biospecimen collection) |
Primary outcome
Characterized germline variants in SMAD6 and their association with Langerhans Cell Histiocytosis (LCH)
Time frame: Up to 4 years
Will re-sequence SMAD6 among LCH case-parent trios to characterize the association between SMAD6 inherited genetic effects and LCH susceptibility using targeted next-generation sequencing. We will also analyze de novo single-nucleotide variants (SNVs), copy-number variants (CNVs), and insertions/deletions(INDELs) obtained through SMAD6 sequence data generated from the biologic samples of the CCRN/PEC LCH case-parent trios.
The frequency of de novo mutations and systematic assessment of the underlying genetic makeup of LCH
Time frame: Up to 4 years
Will use the maximum number of LCH case-parent trios enrolled utilizing the CCRN/PEC with viable biologic samples to conduct genome-wide SNP genotyping. This methodology will identify new genes and pathways associated with LCH susceptibility. We will also determine the prevalence of novel de novo mutations associated with LCH in these case-parent trios. This will provide a systematic assessment of the underlying genetic makeup of LCH in a large sample of families.
The difference in LCH-related somatic mutations by race/ethnicity due to underlying genetic ancestry
Time frame: Up to 4 years
Genetic ancestry will be determined using germline genome-wide SNP array data generated from CCRN/PEC LCH cases in Aim 2. In parallel, we will determine patient somatic mutational profiles using a custom, targeted 91-gene panel. We will then conduct a genome-wide admixture-mapping scan to identify LCH-related loci that are associated with specific LCH somatic mutational profiles.
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 9 Jan 2026.
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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. This study is not recruiting at the moment.
Michael Scheurer, PhD principal investigator
Children's Oncology Group
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 Histiocytosis, Langerhans-Cell, run by Children's Oncology Group 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 7 inclusion and 0 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: under way, not looking for participants, as of the sponsor's last update on 9 Jan 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterized germline variants in SMAD6 and their association with Langerhans Cell Histiocytosis (LCH) (time frame: Up to 4 years). The study lists 3 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 9 Jan 2026.