Clinical trial NCT06392711: Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Medical Xerostomia
Official title: UW23129: a Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Medical Xerostomia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Xerostomia
Graft-versus-host-disease
Sjogren's Disease
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants experiencing DLT of submandibular pain
timeFrame: 1 month post-injection
measure: Proportion of participants experiencing DLT as serious adverse events (AEs)
timeFrame: 1 month post-injection
measure: Proportion of participants experiencing DLT as pre-specified toxicities
timeFrame: 1 month post-injection
Secondary outcomes:
measure: Change in xerostomia scores
timeFrame: Baseline to 24 months
measure: Change in salivary function-rate of salivary production
timeFrame: Baseline, 1 month, 3 moths, 6 months, 12 months, and 24 months
measure: Change in salivary function-saliva composition
timeFrame: Baseline, 1 month, 3 moths, 6 months, 12 months, and 24 months
measure: Change in salivary function-saliva composition
timeFrame: Baseline, 1 month, 3 moths, 6 months, 12 months, and 24 months
measure: Change in salivary function-saliva composition
timeFrame: Baseline, 1 month, 3 moths, 6 months, 12 months, and 24 months
measure: Change in salivary function-saliva composition
timeFrame: Baseline, 1 month, 3 moths, 6 months, 12 months, and 24 months
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Sara McCoy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Jacques Galipeau, MD
role: STUDY_DIRECTOR
References: