Sequential Administration of WJ-MSCs for the Treatment of GvHD Refractory to Second Line Treatment
- Conditions
- Graft Versus Host Disease
- Interventions
- Biological: Wharton's jelly mesenchymal stem cells (WJ-MSCs)
- Registration Number
- NCT06304025
- Lead Sponsor
- Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
- Brief Summary
Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for malignant hemopathies, but highlights the limitations of long-term results due to the high toxicity of the procedure and the development of Graft versus Host Disease (GVHD). Conventional treatments for GVHD have limited success rates, and some patients may be refractory to ruxolitinib, a second-line treatment option. As a result, there is a need to explore alternative immuno-modulatory therapies, such as the use of Wharton's jelly mesenchymal stem cells (WJ-MSCs).
The research question aims to investigate the safety and potential benefits of sequentially infusing thawed or expanding allogeneic WJ-MSCs in the treatment of acute GVHD refractory to second-line treatment in patients from the Colombian population. This pilot clinical study is being conducted to address the unmet need for patients who develop GVHD resistant to ruxolitinib.
- Detailed Description
In recent decades, the number of HSCTs has significantly increased, as it is considered the ideal therapeutic approach for a wide range of hematological diseases. However, GVHD is the most common and severe complication following transplantation, and it remains the major limiting factor for the success of HSCT. It has been reported that the incidence of acute GVHD is approximately 50% in patients who receive HSCT from an HLA-matched donor, and it increases in cases of HLA-mismatched donors, despite having prophylactic treatment. Patients who develop GVHD have a poor prognosis, with a survival rate ranging from 5-25% depending on the severity of the disease. This is strongly related to the lack of effective treatments. In addition to the high morbidity and mortality, GVHD represents a significant financial burden for public healthcare systems worldwide. A recent study in 2018 in the United States reported that the cost of complete remission for a 6-month period with ruxolitinib, one of the most commonly used treatments for both acute and chronic GVHD, was $1,187,657 USD.
In this context, the American Society for Blood and Marrow Transplantation considers MSCs as a prominent therapeutic tool for the treatment of GVHD, as they significantly improve both the symptoms of the most frequently affected organs (skin, liver, and intestines) and the treatment response parameters and overall survival. Colombia is not exempt from this issue; the rise of HSCT in our country is evident. Therefore, the development of a novel and effective therapeutic strategy for GVHD is a priority and demands further scientific research.
Finally, with the development of this pilot study, the aim is to lay the groundwork for conducting medium- and large-scale clinical trials in our Colombian population, where clinical studies with this type of therapeutic approach have not yet been conducted.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
- Patients from the Transplant Unit of the FOSCAL.
- Patients with a diagnosis of hemopathy that has not been controlled by the transplant or is progressing at the time of treatment.
- Bacterial, viral, or fungal infection that is not being controlled with adequate treatment.
- Cardiac and/or pulmonary function in uncontrolled altered conditions.
- According to medical criteria, patients who are not in an adequate situation to tolerate the treatment.
- Pregnant women or women at risk of pregnancy due to inadequate contraceptive measures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Expanding allogeneic WJ-MSCs Wharton's jelly mesenchymal stem cells (WJ-MSCs) Administration intravenously of 1x106 cells/kg weight of expanding allogeneic WJ-MSCs Thawed allogeneic WJ-MSCs Wharton's jelly mesenchymal stem cells (WJ-MSCs) Administration intravenously of 1x106 cells/kg weight of thawed allogeneic WJ-MSCs
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events: safety and tolerability 12 months The trial's primary endpoint is to determine the safety of WJ-MSCs administration; for that, we will assess the number of treatment-related adverse events (AEs) reported according to the Common Terminology Criteria for AE classification and presentation of infectious complications after administration of WJ-MSCs.
Efficacy biological profile: secretion pattern of soluble factors 12 months • Evolution of the secretion pattern of the following soluble factors: cytokines CK8, Reg3α, Elafina, ST2, INF-γ, TNF-α, IL-12, IL-10, CXCL-9 and CXCL-10 (concentration: mg or μg or pg or others).
Efficacy clinic profile: decrease in treatments 12 months • Decrease in corticosteroids or concomitant immunosuppressive treatment (dose).
Efficacy biological profile: ocrrelation of the biological markers with the clinical response 12 months • Correlation of the profile of biological markers with the clinical response (-1 and 1).
Efficacy clinic profile: response of acute GVDH 12 months • Response of acute GVHD refractory to second-line treatment (yes or no).
Efficacy clinic profile : duration of response 12 months • Duration of response/incidence of relapses( time: days or months).
Efficacy biological profile: cell populations 12 months • Determination of the following cell populations: T lymphocytes, Naive, B lymphocytes, dendritic cells, and Natural Killer cells in blood pre and post-treatment with WJ-MSCs (percentage).
- Secondary Outcome Measures
Name Time Method