Unlock the Cell: Castleman's Disease Flow Cytometry Study

Unlock the Cell: Intracellular Inflammatory Pathways and Flow Cytometry Study for Castleman's Disease

Castleman disease, a rare lymphoproliferative disorder, is characterized by inflammatory cytokine production and multiple organ system dysfunction. In this study, we will investigate inflammatory markers, cells, and signaling pathways in prospectively collected blood samples and/or buccal swabs or saliva using biochemical and RT-PCR techniques, proteomics, genomics, immunohistochemistry, storage for future use, cell culture treated with external stimuli, flow cytometry, and other molecular tests

Study Overview

• Status: Completed
• Conditions: Hyperplasia; Castleman Disease; Castleman's Disease; Giant Lymph Node Hyperplasia; Angiofollicular Lymph Hyperplasia; Angiofollicular Lymphoid Hyperplasia; GLNH
• Intervention / Treatment: Procedure: Blood draw/buccal swab

Detailed Description

This is a University of Pennsylvania-sponsored project that is supported by the Castleman Disease Collaborative Network and the patients/loved one's group Castleman's Warriors (Castleman's Awareness and Research Effort).

Castleman Disease (CD) is a rare and poorly understood lymphoproliferative disease. The multicentric CD subtype (MCD) involves enlarged lymph nodes in multiple regions of the body and can be fatal if untreated. MCD patients demonstrate acute inflammatory crisis due to upregulation of inflammatory agents most notably IL-6 and VEGF followed by multiple organ failure and death.

Unlock the Cell aims to identify the pathways the disease takes through flow cytometry studies. The purpose of the CD Research study is to collect blood samples and/or buccal swabs or saliva samples and medical information of MCD patients and compare them to control samples so researchers can understand the causes of MCD, and design treatments based on our findings.

In this study, the investigators will analyze inflammatory markers, cells, and signaling pathways in prospectively collected blood samples using biochemical and RT-PCR techniques, proteomics, genomics, immunohistochemistry, storage for future use, cell culture treated with external stimuli, flow cytometry, and other molecular tests. A secondary aim is to collect excess stored tissue samples (e.g., lymph node, bone marrow) from previous procedures and store these samples along with unused blood samples for future research purposes to be performed at the University of Pennsylvania or shared with other Castleman disease researchers and biobanks.

• Study Type: Observational
• Enrollment (Actual): 130

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals of any age (including those younger than 7 years of age), gender and ethnicity who have been diagnosed with CD

Description

Inclusion Criteria:

• CD patients: Individuals of any age who are diagnosed with or suspected by a physician to have CD, including those who do have the ability to consent and those who lack the ability to consent
• Related Disease: Individuals who state that they have a disease that is a "Related Disease". "Related Disease" means autoimmune, oncology, inflammatory/lymphoproliferative disorders and infectious diseases that are similar to Castleman
• Healthy Individuals: Individuals without a history of auto-immune, inflammatory, infectious disease or oncologic disorders.

Exclusion Criteria:

• All individuals whose medical or psychological conditions (such as a mental handicap) would, in the opinion of the Principal Investigator, compromise the subject's safety or successful participation in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Castleman's Patients; Castleman's patients with HHV8 negative multicentric MCD	Procedure: Blood draw/buccal swab; The research project will need a blood sample of no more than 50mL per two month period. The research project may also request a buccal swab from patients if needed.
Related Disease Controls; Controls with inflammatory diseases similar to idiopathic multicentric Castleman's: i.e. HHV8+ MCD, HLH, Hodgkin disease	Procedure: Blood draw/buccal swab; The research project will need a blood sample of no more than 50mL per two month period. The research project may also request a buccal swab from patients if needed.
Healthy Donor Controls; Healthy subjects used for controls. These healthy subjects have no history of autoimmune disorders.	Procedure: Blood draw/buccal swab; The research project will need a blood sample of no more than 50mL per two month period. The research project may also request a buccal swab from patients if needed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collect PBMCs to use for inflammatory cell profiling via FACS	Peripheral blood will be collected to isolate peripheral blood mononuclear cells (PBMCs) used to look at inflammatory cell profiling via FACS. This will tell us what specific profiles are dysregulated.	1 year ~
Collect PBMCs to use for cell culture experiments	Peripheral blood will be collected to isolate peripheral blood mononuclear cells (PBMCs) for cell culture experiments.	1 year ~

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use peripheral blood for biochemical testing	Biochemical testing will be performed on blood samples to collect inflammatory gene expressions using qPCR, ELISA and immunoblot.	1 year ~
Extract DNA and RNA from tissue samples to store in biobank	Excess blood sample tubes and/or buccal swabs or saliva will have DNA and RNA extracted and serum and plasma separated out to be stored in our biobank for future research.	1 year ~

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Castleman Disease Collaborative Network
• Investigators: Principal Investigator: Vera Krymskaya, PhD, MBA, University of Pennsylvania

Publications and helpful links

Helpful Links

• Hunt I: Columbia Hunt Pathogen Study
• Predictors of response to siltuximab
• The full spectrum of Castleman Disease: 273 patients studied over 20 years
• Effectiveness of rituximab-containing treatment regimens in iMCD
• iMCD International Treatment Guidelines

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): January 30, 2019
• Study Completion (Actual): March 30, 2019

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 29, 2016
• First Posted (Estimate): August 3, 2016

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: CD; MCD; iMCD; Castleman's Disease; Angiofollicular Lymph Hyperplasia; multicentric Castleman's disease; multicentric Castleman disease; Castleman Disease; Unlock the Cell; idiopathic multicentric Castleman disease
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hyperplasia; Castleman Disease; Lymphadenopathy
• Other Study ID Numbers: 823546

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified Researchers, who apply for access to the data and are subsequently approved, will be given access to a limited dataset with direct identifiers removed in an Excel compatible file format or single SAS data files.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)