Sequential Administration of WJ-MSCs for the Treatment of GvHD Refractory to Second Line Treatment

NCT ID: NCT06304025

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-30
• Study Completion Date: 2025-08-31

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Thawed allogeneic WJ-MSCs

Administration intravenously of 1x106 cells/kg weight of thawed allogeneic WJ-MSCs

Group Type: EXPERIMENTAL

Wharton's jelly mesenchymal stem cells (WJ-MSCs)

Intervention Type: BIOLOGICAL

Four doses of 1x10 6 of thawed allogeneic WJ-MSCs or expanding allogeneic WJ-MSCs / kg at 1, 4, 11, and 18 days

Expanding allogeneic WJ-MSCs

Administration intravenously of 1x106 cells/kg weight of expanding allogeneic WJ-MSCs

Group Type: EXPERIMENTAL

Wharton's jelly mesenchymal stem cells (WJ-MSCs)

Intervention Type: BIOLOGICAL

Four doses of 1x10 6 of thawed allogeneic WJ-MSCs or expanding allogeneic WJ-MSCs / kg at 1, 4, 11, and 18 days

Interventions

Wharton's jelly mesenchymal stem cells (WJ-MSCs)

Four doses of 1x10 6 of thawed allogeneic WJ-MSCs or expanding allogeneic WJ-MSCs / kg at 1, 4, 11, and 18 days

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Aged between 18 and 65 years.
• With a diagnosis of malignant hemopathies, who have undergone allogeneic HSCT and who are diagnosed with acute GVHD refractory to second-line treatment.
• Patients who have received bone marrow and/or peripheral blood as a source of cells.
• Patients who have received cells from a family or unrelated donor
• Myeloablative or non-myeloablative conditioning method.
• Adequate cardiac function without evidence of uncontrolled hypertension, congestive heart failure, angor pectoris, or acute myocardial infarction in the 6 months prior to the process.
• Adequate lung function without evidence of severe obstructive or restrictive lung disease.
• Informed consent signed by the patient.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud - IDCBIS

OTHER

Sponsor Role: collaborator

Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

OTHER

Sponsor Role: lead

Responsible Party

Martha Ligia Arango Rodríguez

Scientific technical director of the Center for advanced therapies Fundación Oftalmológica de Santander (FOSCAL)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

GvHD 01

Identifier Type: -

Identifier Source: org_study_id