Mesenchymal Stem Cells as a Treatment for Oral Complications of Graft-versus-host Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Karolinska Institutet
Sponsor:
Collaborator:
Stockholm County Council, Sweden
Information provided by (Responsible Party):
Rachael Sugars, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT02055625
First received: February 4, 2014
Last updated: NA
Last verified: February 2014
History: No changes posted
  Purpose

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT), and is classified as acute (aGVHD) or chronic (cGVHD). aGVHD onsets within the first 100 days after transplant or with clinical features including erythema, liver dysfunction and oral mucositis, whilst cGVHD or persistent GVHD occurs in approximately 30-60% of transplant patients who survive their first year . Long-term five-year prognosis for cGVHD patients is poor with a 70% mortality rate. cGVHD manifests as an autoimmune-like disease affecting multiple sites, including skin, mouth, eyes, gastrointestinal tract, liver, and joints. The oral cavity is the second most common site to be affected with symptoms in 45-83% of cases. In the mouth a diverse spectrum of clinical features can be found for example mucosal lesions can affect almost any site, salivary gland dysfunction and restricted mouth opening. Short-term patients can experience mucosal sensitivity, malnutrition, problems speaking, increased caries risk, xerostomia, oral pain and a diminished quality-of-life. Long-term complications include secondary malignancies and perhaps early death. Clinical management seeks to alleviate the symptoms and improve quality-of-life but 50% of patients fail front-line systemic steroid therapy. Oral cGVHD can be treated with topical high potency corticosteroids and oral rinses, however these treatments are not always effective and carry a risk of systemic absorption. Mesenchymal stem/stromal cells (MSCs) resident in adult and fetal tissues, such as the bone marrow have the capacity to form bone, cartilage, stroma, muscle and fat, are known to exhibit immunosuppressive and immunoregulatory properties both in vivo and in vitro. MSC infusions have been used to treat disorders such as osteogenic imperfecta, cardiovascular disease and to heal large bony defects. Indeed, the immunosuppressive capacity of MSCs have led to infusions being used as a second-line treatment for GVHD patients, and our group has shown within a Phase II clinical trial, 55% aGVHD patients who failed front-line steroid treatment responded to MSC infusion these studies are going with cGVHD patients. The goal of this project is to perform a pilot study to determine whether MSC injections directly into mucosal lesions in patients with oral cGVHD are able to alleviate the symptoms and facilitate the reparative process.


Condition Intervention Phase
Graft -Versus-host-disease
Biological: Mesenchymal stromal cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Oral Mucosa in Patients With Graft-versus-host Disease Following Injection of Mesenchymal Stem Cells - Human Pilot Study

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • Change in disease activity according to National Institutes of Health criteria for oral graft-versus-host disease [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in self-assessed disease activity and quality of life [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Baseline to 21 months ] [ Designated as safety issue: Yes ]
    Frequency of complications, infections and relapse


Estimated Enrollment: 12
Study Start Date: January 2014
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mesenchymal stromal cell treatment
Biological: Mesenchymal stromal cells
Biological: Mesenchymal stromal cells
Allogenous mesenchymal stromal cells will be injected directly underneath the mucosal lesions at one side under local anesthetic at 2.5-4 million cells/ml. A total of approximately 1.7 ml will be injected divided in 2-3 injections around the lesion. Patients will be followed every second day up to 7 days afterwards and then routinely at 14 days, 1 month, 2 months and 6 months to assess the healing process.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic graft-versus-host disease and oral manifestations grade 3 exhibiting severe symptoms, according to the NIH Consensus Working Group for Diagnosis and Staging of cGVHD and have failed frontline therapy

Exclusion Criteria:

  • Active malignancy
  • Fulfilling criteria for previously initiated study for treatment of chronic graft-versus-host disease
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02055625

Contacts
Contact: Karin Garming-Legert, DDS, PhD 0046852488071 karin.garming-legert@ki.se
Contact: Rachael Sugars, BSc, PhD 0046852488123 rachael.sugars@ki.se

Locations
Sweden
Oral and Maxillofacial Surgery, Karolinska Univeristy Hospital Recruiting
Stockholm, Huddinge, Sweden, 14186
Contact: Karin Garming-Legert, DDS, PhD    0046858583956    karin.garming-legert@ki.se   
Principal Investigator: Karin Garming-Legert, DDS, PhD         
Sponsors and Collaborators
Karolinska Institutet
Stockholm County Council, Sweden
Investigators
Principal Investigator: Katarina Le Blanc, Professor Karolinska Institutet
Principal Investigator: Karin Garming-Legert, DDS, PhD Karolinska Institutet
Principal Investigator: Rachael Sugars, BSc, PhD Karolinska Institutet
  More Information

No publications provided

Responsible Party: Rachael Sugars, Associate Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT02055625     History of Changes
Other Study ID Numbers: 2013/1241-31/1
Study First Received: February 4, 2014
Last Updated: February 4, 2014
Health Authority: Sweden: Regional Ethical Review Board
Sweden: The National Board of Health and Welfare

Keywords provided by Karolinska Institutet:
Graft-versus-host-disease
Immune system diseases
Oral

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases

ClinicalTrials.gov processed this record on August 26, 2014