Clinical trial NCT02055625: Mesenchymal Stem Cells as a Treatment for Oral Complications of Graft-versus-host Disease
Official title: Treatment of Oral Mucosa in Patients With Graft-versus-host Disease Following Injection of Mesenchymal Stem Cells - Human Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Graft -Versus-host-disease
Keywords: Graft-versus-host-disease
Immune system diseases
Oral
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Region Stockholm
First posted: 2014-02-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Change in disease activity according to National Institutes of Health criteria for oral graft-versus-host disease
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Change in self-assessed disease activity and quality of life
timeFrame: Baseline to 6 months
measure: Safety
timeFrame: Baseline to 21 months
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Oral and Maxillofacial Surgery, Karolinska Univeristy Hospital
state: Huddinge
Study officials:
affiliation: Karolinska Institutet
name: Katarina Le Blanc, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Karin Garming-Legert, DDS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Rachael Sugars, BSc, PhD
role: PRINCIPAL_INVESTIGATOR
References: