Allogeneic Mesenchymal Stem Cells for Radiation-induced Hyposalivation and Xerostomia/Dry Mouth

Xerostomia Clinical Trial

— MESRIX-SAFETY  

Official title:

A Phase I Open Label Study Evaluating the Safety and Feasibility of Allogeneic Mesenchymal Stem Cells for Radiation-induced Hyposalivation and Xerostomia in Previous Oropharynx Cancer Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03874572
• Other study ID #: CVB2018-2
• Secondary ID: 2018-003856-19
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 18, 2019
• Est. completion date: December 1, 2025

Study information

• Verified date: September 2020
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An investigator-initiated, non-randomized, open label study to investigate the safety, feasibility and tolerability of intraglandular injection of allogeneic mesenchymal stem/stromal cells (MSCs) into the submandibular and parotid glands of the patients with radiation-induced hyposalivation and xerostomia after radiation for a oropharyngeal squamous cell carcinoma

Description:

Patients with previous oropharyngeal cancer and radiation-induced hyposalivation and xerostomia (dry mouth syndrome) will receive intraglandular injections of allogeneic adipose-derived MSCs into the submandibular and parotid glands. The trial will be Good Clinical Practice (GCP) Monitored. From healthy donors, MSCs will be produced at a Good Manufacturing Practice (GMP) Facility. The patients will be followed for four months for safety, tolerability, and efficacy registration. Changes in quality of life, unstimulated, and stimulated whole saliva flow rate, salivary gland function will be assessed. Immune response towards receiving allogeneic MSCs will be evaluated in plasma and saliva. Changes in the composition and quality of the whole saliva will be investigated. Saliva from the participants will altså be compared to saliva from ten healthy controls.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: December 1, 2025
• Est. primary completion date: June 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age between 18-75 years

2. Previous radiotherapy +/- chemotherapy for OPSCC stage I- II (UICC-8, 2017)

3. 2 years' follow-up without recurrence

4. Clinically reduced salivation and hyposalivation, evaluated by a screening

5. Unstimulated salivary flow rate between 0.2mL/min and 0.05mL/min

6. Grade 2-3 xerostomia (CTCAEv5.0)

7. WHO Performance status (PS) 0-1

8. Informed consent

Exclusion Criteria:

1. Any cancer in the previous 4 years (not including OPSCC and basocellular carcinomas)

2. Xerogenic medications

3. Penicillin or Streptomycin allergy

4. Any other diseases of the salivary glands, e.g. Sjögren's syndrome or sialolithiasis

5. Previous parotid or submandibular gland surgery

6. Previous treatment with any type of stem cells

7. Breastfeeding, Pregnancy or planned pregnancy within the next 2 years

8. Smoking within the previous 6 months.

9. Alcohol abuse (consumption must not exceed 7 units/week for women and 14 units/week for men (Danish National board health alcohol guidelines3)

10. Any other disease/condition judged by the investigator to be grounds for exclusion

Related Conditions & MeSH terms

• Dry Mouth
• Hyposalivation
• Mesenchymal Stem Cells
• Mesenchymal Stromal Cells
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Salivary Gland Diseases
• Stem Cells
• Xerostomia
• Xerostomia Due to Radiotherapy

Intervention

Biological:
• Allogeneic adipose derived stem/stromal cells
Culture expanded allogeneic adipose derived stem/stromal cells

Locations

Country	Name	City	State
Denmark	Department of Otolaryngology, Rigshospitalet	Copenhagen
Denmark	Department of Otolaryngology, Rigshospitalet, University Hospital of Copenhagen	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Number of patients with serious adverse events	Registration of number of patients with serious adverse events in a 4 months follow-up period	4 months
Secondary	Immune reponse :Development of donor specific antibodies	Registration of development of tissue antibodies towards donor cells	4 months
Secondary	Efficacy: Change in Unstimulated Whole Salivary flow rate	Unstimulated whole saliva flow rate is assessed by sialometry	4 months
Secondary	Efficacy: Change in Stimulated Whole Salivary flow rate	Unstimulated whole saliva flow rate is assessed by sialometry	4 months
Secondary	Efficacy: Change in quality of life	Change in quality of life evaluted by QLQ-H&N-35 and XQ questionnaires	4 months
Secondary	Efficacy: Salivary gland function	Assessed by salivary gland 99mTc scintigraphy	4 months
Secondary	Efficacy: Change in Saliva composition	Change in inorganic saliva composition	4 months
Secondary	Efficacy: Change in Saliva Proteomics	Change in Saliva proteomics	4 months
Secondary	Efficacy: Change in RNA in Saliva	Change in RNA in saliva	4 months
Secondary	Immune reponse	Reactions in plasma and saliva will be assessed	4 months