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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer; Xerostomia
• Intervention / Treatment: Drug: MSC

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cancer Connect; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin Carbone Cancer Center
      • Principal Investigator: Randall Kimple, MD, PhD
      • Contact: Cancer Connect; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal Stem Cell (MSC) injection	Drug: MSC; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute of Dental and Craniofacial Research (NIDCR)
• Investigators: Principal Investigator: Randall Kimple, MD, PhD, University of Wisconsin, Madison; Study Director: Jacques Galipeau, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2023
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: April 6, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Head and Neck Neoplasms; Xerostomia
• Other Study ID Numbers: 2023-0194; A533300 (Other Identifier: UW Madison); SMPH/HUMAN ONCOLOGY/HUMAN ONCO (Other Identifier: UW Madison); UW21144 (Other Identifier: UW Madison); 4UH3DE030431-02 (U.S. NIH Grant/Contract); Protocol Version 10/11/2023 (Other Identifier: UW Madison)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No