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

Study Overview
=================
Brief 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

Detailed 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.

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

Conditions
-----------------
Xerostomia Due to Radiotherapy, Hyposalivation, Xerostomia, Oropharynx Cancer, Salivary Gland Diseases, Dry Mouth, Mesenchymal Stem Cells, Mesenchymal Stromal Cells, Stem Cells

Intervention / Treatment
-----------------
* Biological: Allogeneic adipose derived stem/stromal cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18-75 years Previous radiotherapy +/- chemotherapy for OPSCC stage I- II (UICC-8, 2017) 2 years' follow-up without recurrence Clinically reduced salivation and hyposalivation, evaluated by a screening Unstimulated salivary flow rate between 0.2mL/min and 0.05mL/min Grade 2-3 xerostomia (CTCAEv5.0) WHO Performance status (PS) 0-1 Informed consent Exclusion Criteria: Any cancer in the previous 4 years (not including OPSCC and basocellular carcinomas) Xerogenic medications Penicillin or Streptomycin allergy Any other diseases of the salivary glands, e.g. Sjögren's syndrome or sialolithiasis Previous parotid or submandibular gland surgery Previous treatment with any type of stem cells Breastfeeding, Pregnancy or planned pregnancy within the next 2 years Smoking within the previous 6 months. Alcohol abuse (consumption must not exceed 7 units/week for women and 14 units/week for men (Danish National board health alcohol guidelines3) Any other disease/condition judged by the investigator to be grounds for exclusion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic mesenchymal stem/stromal cell therapy<br>Treatment with intra-glandular Injections of allogeneic adipose derived stem cells | Biological: Allogeneic adipose derived stem/stromal cells<br>* Culture expanded allogeneic adipose derived stem/stromal cells<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune reponse :Development of donor specific antibodies | Registration of development of tissue antibodies towards donor cells | 4 months | 
| Efficacy: Change in Unstimulated Whole Salivary flow rate | Unstimulated whole saliva flow rate is assessed by sialometry | 4 months | 
| Efficacy: Change in Stimulated Whole Salivary flow rate | Unstimulated whole saliva flow rate is assessed by sialometry | 4 months | 
| Efficacy: Change in quality of life | Change in quality of life evaluted by QLQ-H&N-35 and XQ questionnaires | 4 months | 
| Efficacy: Salivary gland function | Assessed by salivary gland 99mTc scintigraphy | 4 months | 
| Efficacy: Change in Saliva composition | Change in inorganic saliva composition | 4 months | 
| Efficacy: Change in Saliva Proteomics | Change in Saliva proteomics | 4 months | 
| Efficacy: Change in RNA in Saliva | Change in RNA in saliva | 4 months | 
| Immune reponse | Reactions in plasma and saliva will be assessed | 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Xerostomia Due to Radiotherapy