Molecular Basis of Langerhans and Non-Langerhans Cell Histiocytic Neoplasms and Castleman Disease

Study Overview
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Brief Summary
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The purpose of this study is to use agnostic genomic evaluation using whole exome sequencing (WES) of a variety of rare hematologic diseases grouped under rare blood diseases and its variants to further elucidate the understanding of the chemistry of these disorders and identify potential actionable mutations that can be targeted with therapies in the context of clinical trials.

Detailed Description
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The study team will examine genetic changes, also known as mutations, in the DNA of participants' blood, or if applicable, bone marrow specimen. These types of tests are increasingly used by doctors to improve the accuracy of diagnosis and make decisions during care. This study seeks to understand how many patients will benefit from this testing, and in what ways. The results of this portion of the study are placed in the individual's medical record and are communicated back to each participant.

Official Title
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Exploratory Analysis of the Molecular Basis of Langerhans and Non-Langerhans Cell Histiocytic Neoplasms and Castleman Disease

Conditions
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Castleman's Disease (CD), Langerhans Cell Histiocytosis (LCH), Non-Langerhans-Cell Histiocytosis

Intervention / Treatment
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* Diagnostic Test: Genetic testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have histopathologic confirmation of the particular rare hematologic disease. Diseases that will be considered as rare hematologic diseases for this study will include the following Langerhans cell histiocytosis (LCH) Erdhiem Chester disease (ECD) Rosai-Dorfman disease (RDD) Miscellaneous histiocytic entities -indeterminate dendritic cell tumor, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, fibroblastic reticular cell tumor Unicentric Castleman disease Multicentric Castleman disease including TAFRO Follicular Dendritic Cell sarcoma (FDCS) Newly diagnosed treatment naïve patients as well as patients who received prior therapies (e.g. chemotherapy, targeted therapy, surgery, or radiation) will be included. -Tissue specimens collected within the past 5 yearse will be considered acceptable for study inclusion will include the following Collected as part of the evaluation for diagnostic confirmation Tissue specimen or extracted DNA (from blood sample) banked in IRB approved tissue repositories and obtained within five years prior to the date of informed consent. -Tissue samples are planned to be collectedfrom previously stored surgical specimens already being stored in pathology lab Consent to have germline testing performed in parallel to tumor testingg)Patients willing to receive treatmen Exclusion Criteria: Life expectancy of less than 6months Patient unwilling to have germline testing performed on peripheral blood or buccal mucosa

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genomic analysis<br>When a participant's disorder was diagnosed, blood or tissue specimen was collected. A part of the tissue or blood will be sent to an outside company, Tempus, to be tested for specific genetic changes and the results will be sent back to participants' physician. | Diagnostic Test: Genetic testing<br>* Genetic testing of blood or tissue sample and limited medical information sent to an outside company. Database will link genome sequence data with human trait information, including cancer and other diseases, to be sent to participant's physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of genomic analyses yielding genetic aberrations | Proportion of genomic analyses yielding actionable genetic aberrations. Actionable is defined as a mutation linked to an approved therapy in the particular disease under study or another disease, a known or suspected contraindication to a given therapy, or a clinical trial linked to the alteration | Up to 12 months from last participant accrued | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of genomic analyses yielding actionable genetic aberrations | Actionable will be defined as a mutation linked to an approved therapy in the particular disease or another disease, a known or suspected contraindication to a given therapy, or a clinical trial linked to the alteration. | Up to 12 months from last participant accrued | 
| Proportion of genomic analyses yielding germline genetic aberrations |  | Up to 12 months from last participant accrued | 
| Referral rates for genetic counseling for germline mutations | Number of participants with germline mutations who were referred to genetic counseling through Cancer Genetics for their identified germline mutations | Up to 12 months from last participant accrued | 
| Completion rates of genetic counseling for germline mutations | Number of participants with germline mutations who were referred to, and underwent (completed) genetic counseling through Cancer Genetics. | Up to 12 months from last participant accrued |