MSC in Patients With Xerostomia Post XRT in Head and Neck Cancer

NCT04489732 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 8 other identifiers: 2020-1290A533300SMPH/HUMAN ONCOLOGY/HUMAN ONCOUW20025NCI-2021-000701UG3DE030431-01Protocol Version 9/28/2023Head & Neck SPORE
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center pilot study designed to determine the safety and tolerability of autologous bone marrow-derived Mesenchymal Stromal Cells (MSCs) in patients with xerostomia (dry mouth) after undergoing radiation therapy (XRT) for head and neck cancer (HNC). Up to 12 participants will be enrolled and can expect to be on study for up to 2 years.

Conditions

Xerostomia Following Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects Experiencing Dose Limiting Toxicity (DLT)

  Dose limiting toxicity is defined as: submandibular pain \> 5 on a pain scale of 0-10 at 1-month after MSC injection OR any serious AE OR any of the selected toxicities listed per protocol within one-month post-injection.

  up to 1 month post injection (up to 3 months from consent)

Secondary Outcomes (11)

• Change in Saliva Production Rate

  baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

• Saliva Composition Analysis: Change in Salivary pH

  baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

• Saliva Composition Analysis: Change in Total Protein Concentration in Saliva

  baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

• Saliva Composition Analysis: Change in Amylase Concentration in Saliva

  baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

• Saliva Composition Analysis: Change in Mucin Concentration in Saliva

  baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

Study Arms (1)

Treatment with MSCs

EXPERIMENTAL

A single dose of MSCs injected into the submandibular glands of patients with radiation-induced xerostomia (primary objective) Following primary outcomes, a second injection of 10 (8 - 12) x 106 MSCs will be offered for injection into each participant's contralateral submandibular gland.

Biological: Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells

Interventions

Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells BIOLOGICAL

Single dose, starting at * Dose Level 0: 10 (8-12) x 10\^6 injected into one submandibular gland on Day 1 Sub-study for second injection after primary objectives met, 10 (8 - 12) x 10\^6 MSCs will be offered for injection into each participant's contralateral submandibular gland

Treatment with MSCs

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Histological diagnosis of Head and Neck Cancer (HNC) and ≥ 2 years from completion of treatment for HNC, either clinically or radiologically No Evidence of Disease (NED), as assessed by ENT or Radiation Oncologist within 28 days of study registration
• Individuals at least 18 years of age and no older than 90 years of age
• Xerostomia defined as less than or equal to 80 percent of baseline (pre-radiation) salivary function per patient estimate
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia
• Radiographically confirmed bilateral submandibular glands
• Females of childbearing potential must agree to have a negative urine or serum pregnancy test within 7 days prior to bone marrow biopsy. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• has not undergone a hysterectomy or bilateral oophorectomy; or
• has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Women of childbearing potential in sexual relationships with men must have used an acceptable method of contraception for 30 days prior to study registration and agree to use an acceptable method of contraception until 4 weeks after completing study treatment. Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception.
• Note: Acceptable method of contraception includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy)

You may not qualify if:

• History of sialolithiasis
• Patients with one submandibular gland
• History of autoimmune diseases affecting salivary glands, including Sjögren's syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, and amyloidosis
• Chronic graft vs host disease
• Untreated oral candidiasis
• Use of anti-cholinergic medications (e.g. atropine, ipratropium, oxybutynin, scopolamine, solifenacin, tiotropium, etc…) while enrolled on study
• Malignancy within the past 2 years, except adequately treated stage I lung cancer, low risk prostate cancer that has been treated or is undergoing active surveillance, adequately treated non-melanoma skin cancer, adequately treated ductal carcinoma in situ (DCIS), or adequately treated stage I cervical cancer
• Expected life expectancy ≤ 6 months
• Lidocaine allergy
• Use of investigational drugs, biologics, or devices within 30 days prior to enrollment
• Women who are pregnant, lactating or planning on becoming pregnant during the study
• Not suitable for study participation due to other reasons at the discretion of the investigators

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Related Publications (2)

• Blitzer GC, Glazer T, Burr A, Gustafson S, Ganz O, Meyers R, McDowell KA, Nickel KP, Mattison RJ, Weiss M, Chappell R, Rogus-Pulia NM, Galipeau J, Kimple RJ. Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): A pilot, first-in-human study of interferon gamma-stimulated marrow mesenchymal stromal cells for treatment of radiation-induced xerostomia. Cytotherapy. 2023 Nov;25(11):1139-1144. doi: 10.1016/j.jcyt.2023.07.009. Epub 2023 Aug 15.

  PMID: 37589639 DERIVED

• Blitzer GC, Rogus-Pulia NM, Mattison RJ, Varghese T, Ganz O, Chappell R, Galipeau J, McDowell KA, Meyers RO, Glazer TA, Kimple RJ. Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study protocol for a phase 1 dose-escalation trial of patients with xerostomia after radiation therapy for head and neck cancer: MARSH: Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction. Cytotherapy. 2022 May;24(5):534-543. doi: 10.1016/j.jcyt.2021.11.003. Epub 2022 Feb 16.

  PMID: 35183442 DERIVED

Results Point of Contact

• Title: Randy Kimple, MD, PhD, FASTRO
• Organization: University of Wisconsin Carbone Cancer Center

rkimple@humonc.wisc.edu

608-263-5361

Study Officials

• Randall J Kimple, MD,PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Jacques Galipeau, MD

  University of Wisconsin, Madison

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single-center, open-label, non-randomized, non-placebo controlled, single-group assignment, pilot study

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 28, 2020
• Study Start: February 18, 2022
• Primary Completion: November 22, 2022
• Study Completion: May 1, 2026
• Last Updated: April 8, 2026
• Results First Posted: February 23, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)