Clinical trial NCT04100408: Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)
Official title: Inherited Genetic Susceptibility in Langerhans Cell Histiocytosis (LCH)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Histiocytosis, Langerhans-Cell
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
First posted: 2019-09-24
Enrollment: 647
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with Langerhans cell histiocytosis (LCH) on or after January 1, 2008.

Brief 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. 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:

I. 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:

I. 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.

Eligibility criteria: Inclusion Criteria:

* ≤ 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.

Primary outcomes:
measure: Characterized germline variants in SMAD6 and their association with Langerhans Cell Histiocytosis (LCH)
timeFrame: Up to 4 years
measure: The frequency of de novo mutations and systematic assessment of the underlying genetic makeup of LCH
timeFrame: Up to 4 years
measure: The difference in LCH-related somatic mutations by race/ethnicity due to underlying genetic ancestry
timeFrame: Up to 4 years
Secondary outcomes:
Other outcomes:
measure: The role of genetic ancestry on LCH-related somatic mutations
timeFrame: Up to 4 years
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
Study officials:
affiliation: Children's Oncology Group
name: Michael Scheurer, PhD
role: PRINCIPAL_INVESTIGATOR
References: