Bone Marrow Cells for Radiation-Induced Dry Mouth

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Disqualifiers: Salivary gland disease

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for radiation-induced dry mouth?

Preliminary studies suggest that mesenchymal stem cells (MSCs) can improve salivary function in patients with radiation-induced dry mouth. Additionally, MSCs have been shown to help repair radiation-induced damage in various tissues, including the salivary glands, in animal models. ^{1 2 3 4 5}

Is it safe to use bone marrow-derived mesenchymal stem cells for treating radiation-induced dry mouth?

Studies have shown that bone marrow-derived mesenchymal stem cells (BM-MSCs) are generally safe for use in humans, including those with radiation-induced dry mouth. Clinical trials have demonstrated their normal function and safety profile, and they have been used in various conditions with a focus on safety. ^{1 3 4 6 7}

How is the treatment with bone marrow-derived mesenchymal stem cells different from other treatments for radiation-induced dry mouth?

This treatment is unique because it uses bone marrow-derived mesenchymal stem cells (special cells that can develop into different types of tissues) activated by interferon gamma (a protein that boosts immune response) to potentially repair and restore damaged salivary glands, whereas current treatments mainly provide temporary relief without addressing the underlying damage. ^{2 3 5 8 9}

Research Team

Randall Kimple, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Jacques Galipeau, MD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for adults aged 18-90 with dry mouth after radiation therapy for head and neck cancer. They must be at least 2 years post-treatment, in good health (Karnofsky score ≥70), able to undergo bone marrow collection under local anesthesia, have no current cancer signs, and can consent.

Inclusion Criteria

I had head and neck cancer, was treated with radiation, and now show no signs of the disease.

I have dry mouth with less than 80% of my normal saliva production.

I am between 18 and 90 years old.

Exclusion Criteria

I have a condition affecting my salivary glands.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bone Marrow Collection

Participants undergo a collection of bone marrow using a needle

1 day

1 visit (in-person)

MSC Injection

Injection of mesenchymal stem cells into salivary glands

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and tolerability, including pain and adverse events

1 month

Multiple visits (in-person)

Long-term Follow-up

Participants are monitored for changes in quality of life and salivary production

24 months

Visits at 3, 6, and 12 months (in-person)

Treatment Details

Interventions

• MSC

Trial Overview The study tests the safety of injecting mesenchymal stem cells (MSCs) from patients' own bone marrow into their salivary glands to treat dry mouth caused by radiation. It includes collecting bone marrow, donating saliva, ultrasound exams, and questionnaires over a period of up to 30 months.

Participant Groups

Group I: Mesenchymal Stem Cell (MSC) injection Experimental Treatment 1 Intervention

MSC is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in European Union as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in Canada as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in Japan as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in China as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

Findings from Research

The study involving 30 patients with radiation-induced xerostomia showed that autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections are safe, with no serious adverse events linked to the treatment over a follow-up period of at least 2 years.

Patients receiving ASC therapy reported a significant reduction in xerostomia symptoms and a slight increase in saliva flow rates compared to the placebo group, indicating a clinically relevant benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial. Lynggaard, CD., Grønhøj, C., Jensen, SB., et al.[2023]

Adipose tissue-derived mesenchymal stromal cells (aMSCs) significantly reduced the duration of radiation-induced oral mucositis (RIOM) in a mouse model, with a 72% decrease in ulcer duration from 5.6 days to 1.6 days after treatment.

The effectiveness of aMSCs therapy was influenced by factors such as dose size, frequency, and timing of administration, and importantly, the treatment did not promote the growth of head and neck cancer cells in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis. Maria, OM., Shalaby, M., Syme, A., et al.[2018]

The MARSH trial is a first-in-human study assessing the safety and tolerability of bone marrow-derived mesenchymal stromal cells (BM-MSCs) activated by interferon-γ for treating radiation-induced xerostomia in head and neck cancer patients, involving 21 to 30 subjects.

This innovative therapy aims to restore salivary gland function and improve quality of life, potentially offering a curative option for xerostomia, which currently lacks effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Blitzer, GC., Rogus-Pulia, NM., Mattison, RJ., et al.[2023]

This systematic review aims to evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for treating salivary gland hypofunction caused by radiation injury, focusing on salivary flow rates as the primary outcome.

The review will analyze existing animal studies to provide insights into the effectiveness and safety of MSC treatment, which could help optimize future clinical trials for patients suffering from dry mouth after head and neck radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal/stem cell therapy for radiation-induced salivary gland hypofunction in animal models: a protocol for a systematic review and meta-analysis. Jansson, PM., Lynggaard, CD., Carlander, AF., et al.[2022]

The pilot study involving 6 patients with radiation-induced xerostomia showed that injecting autologous IFNγ-stimulated mesenchymal stromal/stem cells (MSC(M)) into the submandibular gland is safe, with no serious adverse events reported within a month after the injection.

There was a trend towards increased salivary production and improved quality of life in half of the patients, suggesting potential efficacy of MSC(M) treatment for alleviating dry mouth symptoms in head and neck cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Blitzer, GC., Glazer, T., Burr, A., et al.[2023]

Multipotent mesenchymal stromal cells (MSCs) show promising therapeutic effects for treating side effects of radiation, particularly in acute radiation reactions, based on a review of both experimental and clinical data.

MSCs can be administered either locally or systemically to irradiated organs and tissues, demonstrating protective and regenerative effects, with various mechanisms of action being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic Effects of Multipotent Mesenchymal Stromal Cells after Irradiation]. Kalmykova, NV., Alexandrova, SA.[2018]

This study will evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) from umbilical cord tissue in treating xerostomia in 10 oropharyngeal cancer patients who have experienced dry mouth after radiotherapy.

The innovative approach of using MSCs aims to improve salivary flow and quality of life for patients, with assessments planned for toxicity, salivary composition, and tissue characteristics over a 4-month period, potentially offering advantages over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial. Strojan, P., Plavc, G., Kokalj, M., et al.[2023]

Cell-derived vesicles (CDVs) from adipose-derived mesenchymal stem cells (ADMSCs) effectively restored the proliferation and function of irradiated salivary gland (SG) epithelial cells in vitro, indicating their potential as a radioprotective treatment.

The study showed that ADMSC-CDVs not only improved cell proliferation and amylase activity in irradiated SG cells but also restored transepithelial electrical resistance (TEER), suggesting a comprehensive protective effect against radiation damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage. Kim, JM., Choi, ME., Jeon, EJ., et al.[2022]

Bone marrow-derived clonal mesenchymal stem cells (BM-cMSCs) significantly improved salivary flow rates in mice with irradiation-induced salivary gland damage, indicating their potential efficacy in treating xerostomia.

The study demonstrated that BM-cMSCs not only preserved the structure of salivary glands but also transdifferentiated into functional salivary epithelial cells, suggesting a mechanism of action that supports tissue repair and restoration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. Lim, JY., Yi, T., Choi, JS., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis. [2018]

3. England pubmed.ncbi.nlm.nih.gov

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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal/stem cell therapy for radiation-induced salivary gland hypofunction in animal models: a protocol for a systematic review and meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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. [2023]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Therapeutic Effects of Multipotent Mesenchymal Stromal Cells after Irradiation]. [2018]

7. Poland pubmed.ncbi.nlm.nih.gov

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. [2022]