Main Session
Sep 30
SS 37 - Head and Neck 4: Refining Radiation: What Clinical Trials Can Tell Us

315 - Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): A Phase 1 Dose-Escalation Trial of Patients with Xerostomia after Radiation Therapy for Head and Neck Cancer

01:15pm - 01:25pm PT
Room 314

Presenter(s)

Grace Blitzer, MD - University of Wisconsin Madison, Madison, WI

G. C. Blitzer1, T. Glazer2, S. Gustafson2, A. Burr3, R. Pena Chavez2, O. Ganz2, J. L. Murphy2, R. Meyers2, M. Weiss4, L. Sanchez2, C. Kraemer2, K. McDowell2, S. S. McCoy2, R. J. Chappell2, N. Pulia5, J. Galipeau2, and R. J. Kimple6; 1Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI, 2University of Wisconsin, Madison, WI, 3Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 4Department of Human Oncology, University of Wisconsin Hospitals and Clinics, Madison, WI, 5Department of Communication Sciences and Disorders, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 6Department of Human Oncology, University of Wisconsin, Madison, WI

Purpose/Objective(s):

There are no existing effective treatments for radiation-induced xerostomia (RIX), a common side effect of head and neck radiation. Mesenchymal stromal cells (MSCs) exhibit regenerative effects in multiple tissues and may represent an effective cell therapy for the treatment of RIX. Here we present the primary safety and secondary efficacy endpoints of our phase I trial of IFN?-stimulated autologous bone marrow- derived MSCs [MSC(M)] injected into bilateral submandibular glands for the treatment of RIX.

Materials/Methods:

We conducted a single-center phase I dose-escalation clinical trial in a 3+3 design investigating the safety and tolerability of autologous IFN?-stimulated MSC(M). Patients underwent bone marrow aspiration, MSC(M) were then cultured, stimulated with IFN?, and cryopreserved. Banked IFN?-stimulated MSC(M) were thawed, culture rescued for 18 hours, and then injected into bilateral submandibular glands at increasing dose levels. The primary objective was determining the safety/tolerability and defining the recommended phase 2 dose (RP2D) as determined by dose-limiting toxicity (DLT) defined as submandibular pain > 5 on a standard 10-point pain scale or any serious adverse event (SAE) within one month after injection. Secondary objectives included analysis of efficacy as measured by salivary quantification and using validated quality of life instruments.

Results:

Ten patients with radiation-induced xerostomia were enrolled. All had completed radiation at least 2 years prior. The median age was 67 (36-74), 6 (60%) patients were male. MSCs from one patient were unable to be expanded this patient was taken off study prior to injection. Three and six patients were treated at dose levels 1 and 2, respectively. No SAEs or DLTs were reported. Pain was the most common AE, occurring in 6 total patients, 5 with grade 1 and 1 with grade 2. Grade 1 adenopathy occurred in 4 patients. The analysis of secondary endpoints demonstrated an improvement in quality of life and a trend to increased saliva production.

Conclusion:

Injection of autologous IFN?-stimulated MSC(M) at the RP2D into bilateral submandibular glands of patients with RIX is safe and well tolerated. A trend towards an improvement in secondary endpoints of salivary quantity and quality of life was observed at 1 and 3 months after MSC(M) injection. This phase I clinical trial provides support for further investigation into IFN?-stimulated MSC(M) as an innovative, potentially curative, remedy to treat RIX and restore quality of life. A dose expansion cohort at the RP2D is currently enrolling.