Title
A Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Medical Xerostomia

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.

Objective
Primary Objective:
- To evaluate the safety and tolerability of MSCs for subjects with medical xerostomia

Secondary Objectives:
- To evaluate the efficacy of MSCs for treatment of medical xerostomia and salivary hypofunction via quality-of-life (QoL) questionnaires, salivary amount, and salivary compositional analysis
- To assess the imaging characteristics of patients with medical xerostomia after MSC injection using ultrasound
- To assess the feasibility of a future Phase 2 study.

Treatment 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.

Key Eligibility 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 (called "medical" xerostomia in this protocol, for example, resulting from Sjögren's Disease or Graft versus Host Disease)

>/= 18 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

Applicable Disease Sites
Head and Neck

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital