Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy

Study Overview
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Brief Summary
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The goal of this clinical research study is to evaluate the safety and tolerability of injecting certain cells that you produce in your bone marrow called mesenchymal stem cells (MSCs) into your salivary glands. Participants will have head and neck cancer that was treated with radiation therapy, and in this study will: Undergo a collection of bone marrow using a needle; Donate saliva; Undergo a salivary gland ultrasound; and, Complete questionnaires that ask about dry mouth Participants can expect to be in this study for up to 30 months.

Official Title
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A Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients With Xerostomia After Radiation Therapy for Head and Neck Cancer

Conditions
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Head and Neck Cancer, Xerostomia

Intervention / Treatment
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* Drug: MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of histological diagnosis of head and neck cancer (HNC) that was treated with radiation therapy and currently clinically or radiologically no evidence of disease (NED) Xerostomia, defined as patient reported salivary function (pre-treatment) ≤ 80% of healthy (pre-radiation) ≥ 18 years of age, ≤ 90 years of age. Patients ≥ 2 years from completion of radiation therapy for HNC Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia Willing and able to give informed consent Radiographically confirmed submandibular gland(s) Exclusion Criteria: Salivary gland disease (i.e., sialolithiasis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stem Cell (MSC) injection<br> | Drug: MSC<br>* Injection of MSCs into submandibular glands at pre-specified dose level: Dose -1: 5 (4 - 6) x10^6 MSCs (to be used only if Dose level 1 is not tolerated) per gland (0.5 ml) Dose 0: 10 (8 - 12) x10^6 MSCs per gland (1 ml) Dose 1: 20 (16 - 24) x10^6 MSCs per gland (2 ml)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability: Determination of Recommended Phase 2 Dose (RP2D) | RP2D (also called the maximum tolerated dose) of MSCs determined by the proportion of subjects experiencing dose limiting toxicity (DLT) | Up to 1 month post-injection | 
| Safety and Tolerability: Number of subjects with pain >5 on a 0-10 point scale | Incidence of pain assessed as greater than 5 on standard 0-10 point pain scale (0=not at all to 10=worst pain imaginable) | 1 month post-injection | 
| Safety and Tolerability: Number of Serious Adverse Events | Incidence of any serious adverse event | Up to 1 month post-injection | 
| Safety and Tolerability: Number of Treatment-Emergent Pre-Specified Adverse Events | Incidence of pre-specified adverse events | Up to 1 month post-injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life | Efficacy of MSC assessed through University of Michigan Xerostomia Related Quality of Life (XeQOL) scale, which is a 15-item assessment scale with 4 domains. The score is the average of all responses of all domains and can range from 0 to 4, where higher scores indicate increased xerostomia burden. | Baseline to 24 months post-injection | 
| Change in Quality of Life | Efficacy of MSC assessed through the MD Anderson Dysphagia Index (MDADI), which is a 20-item questionnaire designed for evaluating the impact of dysphagia (swallowing ability). Scores range from 20 (extremely low functioning) to 100 (high functioning). | Baseline to 24 months post-injection | 
| Change in Quality of Life | Efficacy of MSC assessed through VAS xerostomia questionnaire, which is an 8-item questionnaire that measures the perception of dry mouth. Scores range from 0-10, with 0 being low dryness and 10 being high dryness. | Baseline to 24 months post-injection | 
| Change in salivary production | Saliva production will be measured by having participants chew inert gum base to the pace of a metronome (70 beats per minute) while expectorating saliva (without swallowing) into the saliva collection aid for 5 minutes total40. Cryovials will be weighed before and after collection and the difference in weight (g) will represent the amount of saliva produced in 5 minutes for each condition. | Baseline to 24 months post-injection | 
| Shear wave velocity with acoustic radiation force impulse | Assess imaging characteristics of submandibular glands after MSC, measured by ultrasound | 3, 6, and 12 months post-injection |