Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Medical Xerostomia

University of Wisconsin (UW)

Status and phase: Enrolling; Phase 1

Conditions: Sjogren's Disease; Xerostomia; Graft-versus-host-disease

Treatments: Biological: Mesenchymal Stromal Cells (MSC) Dose Level 0; Biological: Mesenchymal Stromal Cells (MSC) Dose Level 1

Study type: Interventional

Funder types: Other

Identifiers

NCT06392711

UW23129 (Other Identifier)

SMPH/MEDICINE/RHEUMATOL (Other Identifier)

A534290 (Other Identifier)

2024-0386

Protocol Version 12/20/23 (Other Identifier)

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the safety and tolerability of injecting certain cells produced in bone marrow called mesenchymal stromal cells (MSCs) into salivary glands. The main question it aims to answer is whether injection of MSCs into salivary glands results in any improvement in dry mouth.

Participants will:

• have bone marrow collected using a needle
• undergo a salivary gland ultrasound
• complete questionnaires
• receive an injection of the bone marrow cells into a salivary gland

Full description

This single-center phase I dose-escalation with expansion cohort, open label, non-randomized, non-placebo controlled, single group assignment study will assess the safety and tolerability of mesenchymal stromal cells (MSCs) for treatment of xerostomia, focusing on xerostomia with inflammatory etiology (e.g., Sjögren's disease [SjD], graft-versus-host disease [GVHD]). An initial cohort of subjects (n=6) will receive a unilateral injection of MSCs at dose level 0. If unilateral treatment is tolerated, a dose escalation cohort (n=8-18) will receive bilateral injection of MSCs. Dose escalation will proceed using a standard 3+3 design and once the recommended phase II dose (RP2D) is defined, 12 additional patients will be accrued to the expansion phase.

Following the completion of screening/baseline procedures, eligible participants will undergo bone marrow aspiration in order to obtain MSCs.

The MSC investigational product will be injected into one or both submandibular glands under local anesthesia at the interventional visit.

Enrollment: 36 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Xerostomia, defined as an unstimulated salivary flow of less than or equal to 0.5 mL in 5 minutes

• Xerostomia not resulting from radiotherapy (medical xerostomia) defined as an unstimulated salivary flow ≤0.5 mL/5 minutes documented at any time following Xerostomia diagnosis and prior to enrollment.

• ≥ 18 years of age, ≤ 90 years of age

• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia

• Willing and able to give informed consent

• Radiographically confirmed bilateral submandibular glands

• If female of childbearing potential, negative pregnancy test

• Males and females of childbearing potential willing to use acceptable contraception

• Laboratory Values (within 42 calendar days of enrollment):

  • Hgb ≥ 9 g/dL (5.58 mmol/L)
  • Platelets ≥ 100,000/µL
  • ANC ≥ 1000/µL
  • Lymphocytes ≥ 800/µL
  • PT/INR and PTT within normal limits based on age/sex

Exclusion criteria

• Patients with one submandibular gland
• Sialolithiasis
• Poorly-controlled diabetes mellitus (HBA1c ≥ 7%)
• Patients who initiated any diuretic therapy before developing dry mouth symptoms or ESRD
• Untreated oral candidiasis based on physical exam at enrollment
• Malignancy within the last 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 DCIS, or adequately treated stage I cervical cancer)
• For patients on immunosuppressive therapy, must be on stable dose of immunosuppressive therapy for at least 2 months, allowing for dose adjustments for blood levels of drugs
• Transfusion dependency
• Life expectancy ≤ 6 months as determined by the investigator
• Use of investigational drugs, biologics, or devices within 30 calendar days prior to enrollment
• Pregnant or lactating women or those who plan to become pregnant during the study
• Not suitable for study participation due to other reasons at discretion of investigators.
• Enrollment in another clinical study possibly interfering with the endpoints of this study

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

MSCs Dose Level 0 into one submandibular gland

Active Comparator group

Description:

6 subjects will receive Mesenchymal Stromal Cells (MSC) at Dose Level 0, which is 10 (8-12) x10\^6 MSCs in a single submandibular gland. If this dose is deemed tolerable when injected into a single submandibular gland, this dose will be administered to both submandibular glands in the initial subjects in the dose escalation arm.

Treatment:

Biological: Mesenchymal Stromal Cells (MSC) Dose Level 0

MSCs into both submandibular glands - Dose Escalation Cohort

Active Comparator group

Description:

8-18 subjects in the Dose Escalation phase of study will receive MSCs into both submandibular glands. The initial subjects in this cohort will receive Dose Level 0: 10 (8-12) x10\^6 MSCs/gland. If this dose is tolerated, subsequent subjects will receive Dose Level 1: 20 (16-24) x10\^6 MSCs/gland. The highest tolerated dose (recommended phase II dose or RP2D) will be administered to the subjects in the Expansion Cohort.

Treatment:

Biological: Mesenchymal Stromal Cells (MSC) Dose Level 1

Biological: Mesenchymal Stromal Cells (MSC) Dose Level 0

MSCs into both submandibular glands - Expansion Cohort

Active Comparator group

Description:

12 subjects in Expansion Cohort will receive MSCs into both submandibular glands at the RP2D.

Treatment:

Biological: Mesenchymal Stromal Cells (MSC) Dose Level 1

Biological: Mesenchymal Stromal Cells (MSC) Dose Level 0