Mesenchymal Stromal Cells for the Treatment of Xerostomia after Radiation Therapy for Head and Neck Cancer

Inclusion Criteria

• Willing to provide informed consent
• Willing to comply with all study procedures and be available for the duration of the study
• Histological diagnosis of HNC and ≥ 2 years from completion of radiation treatment for HNC (+/- surgery, +/- chemotherapy), either clinically or radiologically no evidence of disease (NED), as assessed by otolaryngology (ENT) or radiation oncologist within 30 calendar days of enrollment
• Individuals at least 18 years of age and no older than 90 years of age
• Xerostomia defined as ≤ 80% of baseline (pre-radiation) salivary function per patient estimate
• Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia as determined by the investigator
• Radiographically confirmed submandibular gland(s) * Patients with one submandibular gland may enroll in the dose escalation portion of the trial or in the dose expansion cohort
• Females of childbearing potential must agree to have a negative urine or serum pregnancy test within 7 calendar days prior to bone marrow biopsy. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Women of childbearing potential in sexual relationships with men must have used an acceptable method of contraception for 30 calendar days prior to enrollment and agree to use an acceptable method of contraception until 4 weeks after completing study treatment. Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception. * Note: Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 calendar days prior to study enrollment), intercourse with men who underwent vasectomy
• Hemoglobin (Hgb) ≥ 9 g/dL (5.58 mmol/L) (within 42 calendar days of enrollment)
• Platelets ≥ 100,000/uL (within 42 calendar days of enrollment)
• Absolute neutrophil count (ANC) ≥ 1000/uL (within 42 calendar days of enrollment)
• Lymphocytes ≥ 800 /uL (within 42 calendar days of enrollment)
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits based on age/sex (within 42 calendar days of enrollment)

Exclusion Criteria

• History of sialolithiasis
• History of autoimmune diseases affecting salivary glands, including Sjogren’s syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, and amyloidosis
• Chronic graft versus host disease
• Untreated oral candidiasis based on physical exam at enrollment
• Use of anti-cholinergic medications (e.g., atropine, iptratropium, oxybutynin, scopolamine, solifenacin, tiotropium, etc.) that the patient is unwilling to discontinue at least 7 calendar days prior to enrollment and each study visit
• Malignancy within the past 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 ductal carcinoma in situ (DCIS), or adequately treated stage I cervical cancer
• Expected life expectancy =< 6 months as determined by the investigator
• Use of investigational drugs, biologics, or devices within 30 calendar days prior to enrollment
• Women who are pregnant, lactating or planning on becoming pregnant during the study
• Not suitable for study participation due to other reasons at the discretion of the investigators
• Enrollment in another clinical study possibly interfering with the endpoints of this study