Title
A Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Xerostomia After Radiation Therapy for Head and Neck Cancer

Description
A Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Xerostomia After Radiation Therapy for Head and Neck Cancer

Objective
Primary Objective
To evaluate the safety and tolerability of MSCs for subjects with xerostomia after radiation therapy for HNC
Secondary Objectives
To evaluate the efficacy of MSCs for treatment of xerostomia and salivary hypofunction via quality-of-life (QoL) questionnaires, salivary amount, and salivary compositional analysis
To assess the imaging characteristics in HNC patients after MSC injection using ultrasound
To assess the feasibility of a future Phase 2 study.

Treatment This single-center phase I dose-escalation with expansion cohort, open label, non-randomized, nonplacebo controlled, single group assignment study will assess the safety and tolerability of MSCs for treatment of radiation-induced xerostomia in patients who had head and neck cancer. A total of 6-30
subjects (6-18 in dose-escalation portion of the trial, 12 in expansion cohort) will be enrolled at UWMadison. The phase I dose escalation study will be a 3+3 design. Subject accrual will occur over 2.5 years with the total duration of the trial expected to be approximately 4.5 years.

Key Eligibility 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 NED, as assessed by 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
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

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