Plain English Summary
Background and study aims
Acute graft-versus-host disease (aGVHD) is a possible complication of a bone marrow stem cell transplant from another person (allogeneic hematopoietic stem cell transplantation). It is caused by the donated immune cells reacting against the host tissues. It is potentially lethal and around half of stem cell recipients develop it. Acute GVHD typically occurs in the first 100 days after transplant and affects three organs: skin, liver and gastrointestinal (digestive) tract. The first treatment is to use glucocorticoid drugs but half of the patients do not respond to treatment (steroid refractory). The prognosis of patients who develop acute GVHD and do not respond to treatment is dismal. Numerous strategies to treat steroid-refractory aGVHD with a second treatment have been tested, but none have shown an effect. Therefore, there is no established second-line treatment for steroid-refractory acute GvHD. Mesenchymal stromal cells (MSCs) can decrease the activity of most cells of the immune system. The aim of this study is to assess the effectiveness of MSC treatment for steroid-refractory aGVHD.
Who can participate?
Patients aged 18 and older with steroid-refractory aGVHD after hematopoietic stem cell transplantation
What does the study involve?
All participants are treated with mesenchymal stromal cells. Blood samples are taken during treatment and at follow ups. Patients are followed up to assess their response to treatment, relapse and survival rates.
What are the possible benefits and risks of participating?
There are no benefits or risks for participants, but the results could be used to improve the treatment of patients with aGVHD in the future.
Where is the study run from?
Vilnius University Hospital Santaros Klinikos (Lithuania)
When is the study starting and how long is it expected to run for?
October 2013 to November 2022
Who is funding the study?
Hematology and Oncology Research Association of Lithuania
Who is the main contact?
Mr Adomas Bukauskas
Trial website
Contact information
Type
Scientific
Primary contact
Mr Adomas Bukauskas
ORCID ID
http://orcid.org/0000-0001-5857-4638
Contact details
Seliu 29-41
Vilnius
LT-08125
Lithuania
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
TPSL-LTU-2015
Study information
Scientific title
Mesenchymal stromal cells in patients with steroid refractory acute graft versus host disease after allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion
Acronym
Study hypothesis
Mesenchymal stromal cells have been shown to have immunosuppressive effects. Through various mechanisms mesenchymal stromal cells exert an effect on most cells of the immune system and inhibit proliferation, activation, and cytokine release. Donor T cell activation and inflammatory cytokines play a major role in acute graft versus host disease (aGVHD) pathogenesis. The trialists hypothesize that by immunomodulatory properties mesenchymal stromal cells will be effective in controlling steroid refractory aGVHD and will prolong overall survival.
Ethics approval
Vilnius regional Bioethics Committee, 03/11/2015, ref: 1582000-15-814-326
Study design
Observational prospective non-interventional single-center study
Primary study design
Observational
Secondary study design
Longitudinal study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Steroid refractory acute graft versus host disease after hematopoietic stem cell transplantation or donor lymphocyte infusion
Intervention
Patients with steroid refractory acute graft versus host disease were treated with mesenchymal stromal cells as compassionate use medicinal product (standard of care). Doses have not been predetermined in the protocol and follow standard practice. Additionally, blood samples were taken during treatment phase and at follow ups.
Intervention type
Biological/Vaccine
Phase
Drug names
Primary outcome measure
Overall response rate (ORR) to mesenchymal stromal cells, defined as complete response (CR) or partial response (PR) of acute graft versus host disease, measured at D7, D14, D21, D28, D35, D42, D49, D56, 3 months
Secondary outcome measures
Measured at D7, D14, D21, D28, D35, D42, D49, D56, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months and each year thereafter:
1. Overall survival (OS), defined as time from the start of treatment until death from any cause
2. Event free survival, defined as time from the start of treatment until the following events (whichever occurs first): death, hematologic malignancy relapse, no PR/CR by 3 months since the study entry, aGVHD relapse after PR/CR requiring next line treatment, progression to extensive chronic GVHD
Overall trial start date
09/10/2013
Overall trial end date
30/11/2022
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Steroid refractory acute graft versus host disease after hematopoietic stem cell transplantation
2. 18 years old and older
3. Signed informed consent form
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
45
Participant exclusion criteria
Does not meet inclusion criteria
Recruitment start date
09/10/2013
Recruitment end date
10/04/2017
Locations
Countries of recruitment
Lithuania
Trial participating centre
Vilnius University Hospital Santaros Klinikos
Santariskiu 2
Vilnius
LT-08406
Lithuania
Funders
Funder type
Research organisation
Funder name
Hematology and Oncology Research Association of Lithuania (Hematologijos ir onkologijos tyrėjų asociacija LTU)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a peer-reviewed journal in 2018.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/12/2018
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list