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MSCs for Radiation-induced Xerostomia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04489732
Recruitment Status : Not yet recruiting
First Posted : July 28, 2020
Last Update Posted : November 13, 2020
Sponsor:
Collaborators:
University of Wisconsin Program for Advanced Cell Therapy (PACT)
University of Wisconsin Carbone Cancer Center (UWCCC)
University of Wisconsin School of Medicine and Public Health (UWSMPH)
UW Health
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
This is a single center, non-randomized, Phase I dose escalation study to assess the safety and tolerability of a single dose of autologous, bone marrow-derived, interferon gamma-stimulated Mesenchymal Stromal Cells (MSCs) injected into the submandibular glands of patients with radiation-induced xerostomia (dry mouth) following treatment for head and neck cancer (HNC).

Condition or disease Intervention/treatment Phase
Xerostomia Following Radiotherapy Biological: Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells Phase 1

Detailed Description:
Following enrollment in the study, patients with radiation-induced xerostomia will undergo bone marrow aspirate in order to obtain autologous MSCs. In a Current Good Manufacturing Practices (cGMP)-compliant cell manufacturing facility, the bone-marrow derived MSCs will be stimulated with interferon gamma and increased in number (i.e., expanded) prior to cryopreservation. After thawing and recovery in culture, a single dose of MSCs will be injected into the submandibular glands under local anesthesia. The safety and tolerability of MSC injection will be assessed and changes in quality of life and production of saliva will also be evaluated.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 3 + 3 Dose Escalation with Dose expansion cohort
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Trial of Mesenchymal Stromal Cells in Patients With Xerostomia After Radiation Therapy for Head and Neck Cancer
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dry Mouth
Drug Information available for: Interferon

Arm Intervention/treatment
Experimental: Treatment with MSCs
A single dose of MSCs injected into the submandibular glands of patients with radiation-induced xerostomia
Biological: Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells
Submandibular injection of a single dose of autologous, bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells




Primary Outcome Measures :
  1. Percentage of subjects experiencing dose limiting toxicity (DLT) [ Time Frame: Day 30 ± 10 days ]
    Dose limiting toxicity is defined as 1) score > 5 on a standard pain scale of 1-10, or 2) any serious adverse event. The percentage of subjects experiencing DLT will be used to determine the maximum tolerated dose or maximum administered dose. That dose will be the recommended dose for a phase 2 trial (RP2D).


Secondary Outcome Measures :
  1. Change in Saliva production rate [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    Whole saliva production rates will be measured under unstimulated and stimulated saliva collection conditions.

  2. Saliva composition analysis: Change in salivary pH [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    Salivary pH will be measured using a pH meter. The normal range of saliva pH is 6.2-7.6 .

  3. Saliva composition analysis: Change in total protein concentration in saliva [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    ELISA will be used to quantify total protein concentration in saliva. The normal range of total protein in saliva is 2-5 mg/mL.

  4. Saliva composition analysis: Change in amylase concentration in saliva [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    The enzyme-linked immunosorbent assay (ELISA) will be used to quantify amylase concentration in saliva. The normal range of amylase concentration in saliva is 10-150 U/mL.

  5. Saliva composition analysis: Change in mucin concentration in saliva [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    ELISA will be used to quantify mucin concentration in saliva.The normal range of mucin concentration in saliva is 1,000-3,000 ug/mL.

  6. Change in The University of Michigan Xerostomia Related Quality of Life (XeQOL) score [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    The University of Michigan Xerostomia Related Quality of Life (XeQOL) scale is a validated patient-reported assessment 15 item scale with 4 domains: physical functioning, pain/discomfort, personal/psychologic functioning, and social functioning. Participants will answer the questions on a scale of 1-5 (not a all, a little, somewhat, quite a bit, very much) for every item. Higher scores represent greater degree of symptoms.

  7. Change in The MD Anderson Dysphagia Index (MDADI) score [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    The MDADI is a 20-item questionnaire designed for evaluating the impact of dysphagia on the quality of life of patients with head and neck cancer. The MDADI score ranges from 20-100 with a lower scale representing worse dysphagia.

  8. Change in Visual Analogue Scale (VAS) xerostomia score [ Time Frame: at baseline, Day 30 ± 10 days, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    A Visual Analogue Scale questionnaire for subjective assessment of salivary dysfunction. The VAS xerostomia questionnaire is an 8-item questionnaire that provides a validated measure of the perception of dry mouth. Participants will be asked to mark their responses to each item by placing a vertical line on the 100-mm horizontal scale. The VAS ranges from 8-80 with a lower scale representing less dysphagia/symptoms

  9. Change in salivary gland size [ Time Frame: at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose escalation cohorts; at baseline, Day 90 ± 14 days , Day 180 ± 21 days, Day 365 ± 21 days for dose expansion cohort ]
    Salivary gland size measured by ultrasound imaging



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 Head and Neck Cancer (HNC) and ≥ 2 years from completion of treatment for HNC, either clinically or radiologically NED(no evidence of disease)
  • Individuals at least 18 years of age
  • Karnofsky performance status ≥ 60, patient eligible for bone marrow aspirate with wakeful anesthesia
  • Females of childbearing potential must have a negative urine or serum pregnancy test at baseline and prior to enrollment. 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 use an acceptable method of contraception from 30 days prior to enrollment 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: Acceptable method of contraception includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy)

Exclusion Criteria:

  • History of sialolithiasis
  • Expected life expectancy ≤ 6 months
  • Use of investigational drugs, biologics, or devices within 30 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
  • COVID-19 positive (active infection) at baseline evaluation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04489732


Contacts
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Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu

Sponsors and Collaborators
University of Wisconsin, Madison
University of Wisconsin Program for Advanced Cell Therapy (PACT)
University of Wisconsin Carbone Cancer Center (UWCCC)
University of Wisconsin School of Medicine and Public Health (UWSMPH)
UW Health
Investigators
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Principal Investigator: Randall J Kimple, MD,PhD University of Wisconsin, Madison
Study Director: Jacques Galipeau, MD University of Wisconsin, Madison
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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT04489732    
Other Study ID Numbers: UW20025
A533300 ( Other Identifier: University of Wisconsin,Madison )
SMPH/HUMAN ONCOLOGY/HUMAN ONCO ( Other Identifier: University of Wisconsin, Madison )
First Posted: July 28, 2020    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Interferons
Interferon-gamma
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents