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

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.

There is no expanded access program available per this protocol.

Inclusion criteria

• Xerostomia, defined as an unstimulated salivary flow <1.2 mL in 5 minutes documented at any time following xerostomia diagnosis and prior to enrollment
• Xerostomia not resulting from radiotherapy (medical xerostomia)
• ≥ 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 28 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 and are still on diuretic therapy and the referring provider believes the dryness symptoms are driven by diuretic use
• 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