Beta Glucan's Effect on Pembrolizumab Immunologic Response in Stage III-IV Melanoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine how beta-glucan affects the immune system in subjects with melanoma.

Detailed Description
-----------------
This is a clinical pilot study using oral beta-glucan on patients with advanced stage III-IV melanoma without evidence of disease receiving adjuvant Pembrolizumab. The aim is to see whether beta-glucan treatment in combination with Pembrolizumab may provide augmented immunologic phenotypes such as decreased peripheral MDSCs, enhanced T effector cell function, or enhanced cytokine production in the peripheral blood or plasm of enrolled subjects. Secondary outcome measures will include clinical endpoints such as recurrence, progression free survival and overall survival.

Official Title
-----------------
Beta Glucan's Effect on Pembrolizumab Immunologic Response in Stage III-IV Melanoma

Conditions
-----------------
Melanoma Stage III, Melanoma Stage IV

Intervention / Treatment
-----------------
* Dietary Supplement: Beta-Glucan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any patients with suspected (clinical) or definitive (tissue) diagnosis of Stage III-IV melanoma starting or continuing adjuvant Pembrolizumab without active evidence of disease (NED). Must be treatment naïve or have had treatment no less than 6 months prior to enrollment 18 years or older Must be able to take pills ECOG performance status of 0-3 Ability to understand and willingness to sign a written informed consent Members of all racial and ethnic groups are eligible for this study Exclusion Criteria: History of hypersensitivity reactions attributed to beta-glucan Patients receiving continuous or other ongoing immunosuppressive therapy Uncontrolled intercurrent illness including, but not limited to, autoimmune diseases, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Any patients who have serious autoimmune toxicity during the study period, or those who have disease recurrence during the 6-week study period should be excluded and analyzed separately Patients with mucosal melanoma Patients with concurrent malignancy or recent history thereof

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All subjects will undergo 21 days of Pembrolizumab followed by 21 days of beta-glucan. Pembrolizumab: 200 mg/100mL IV in three week intervals Beta-glucan: 500mg (1 capsule) by mouth twice a day for 21 days | Dietary Supplement: Beta-Glucan<br>* 500mg (1 capsule) by mouth twice a day for 21 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in percent of lymphocyte cell surface expression markers | The investigators will quantify percent of lymphocyte cell surface e (i.e., CD45, CD3, CD11b, etc.) from each sample collected by mass cytometry *CyTOF) or flow cytometry | Blood for analysis will be drawn at baseline (Day 0), 3 weeks post pembrolizumab treatment, and 3 weeks post pembrolizumab plus oral beta-glucan treatment. | 
| Changes in absolute number of lymphocyte cell surface expression markers | The investigators will quantify absolute number of lymphocyte cell surface (i.e., CD45, CD3, CD11b, etc.) from each sample collected by mass cytometry (CyTOF) or flow cytometry | Blood for analysis will be drawn at baseline (Day 0), 3 weeks post pembrolizumab treatment, and 3 weeks post pembrolizumab plus oral beta-glucan | 
| Changes in the mean fluorescent intensity of lymphocyte cell surface expression markers | The investigators will quantify mean fluorescent intensity of lymphocyte cell surface (i.e., CD45, CD3, CD11b, etc.) from each sample collected by mass cytometry *CyTOF) or flow cytometry | Blood for analysis will be drawn at baseline (Day 0), 3 weeks post pembrolizumab treatment, and 3 weeks post pembrolizumab plus oral beta-glucan | 
| Changes in percent of intracellular cytokine expression markers | The investigators will quantify percent of intracellular cytokine expression (TNFa, IFNg, etc.) from each sample collected by mass cytometry (CyTOF) or flow cytometry | Blood for analysis will be drawn at baseline (Day 0), 3 weeks post pembrolizumab treatment, and 3 weeks post pembrolizumab plus oral beta-glucan | 
| Changes in absolute number of intracellular cytokine expression markers | The investigators will quantify absolute number of intracellular cytokine expression (TNF-a, IFNg, etc.) from each sample collected by mass cytometry (CyTOF) or flow cytometry | Blood for analysis will be drawn at baseline (Day 0), 3 weeks post pembrolizumab treatment, and 3 weeks post pembrolizumab plus oral beta-glucan | 
| Changes in fluorescent intensity of intracellular cytokine expression markers | The investigators will quantify fluorescent intensity of intracellular cytokine expression (TNF-a, IFNg, etc.) from each sample collected by mass cytometry (CyTOF) or flow cytometry | Blood for analysis will be drawn at baseline (Day 0), 3 weeks post pembrolizumab treatment, and 3 weeks post pembrolizumab plus oral beta-glucan |