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

NCT06304025 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: GvHD 01
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Graft Versus Host Disease

Keywords

Graft-versus-host Disease; Ruxolitinib; Mesenchymal Stem Cells

Outcome Measures

Primary Outcomes (7)

• Incidence of treatment-emergent adverse events: safety and tolerability

  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.

  12 months

• Efficacy clinic profile: response of acute GVDH

  • Response of acute GVHD refractory to second-line treatment (yes or no).

  12 months

• Efficacy clinic profile : duration of response

  • Duration of response/incidence of relapses( time: days or months).

  12 months

• Efficacy clinic profile: decrease in treatments

  • Decrease in corticosteroids or concomitant immunosuppressive treatment (dose).

  12 months

• Efficacy biological profile: secretion pattern of soluble factors

  • 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).

  12 months

• Efficacy biological profile: cell populations

  • 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).

  12 months

• Efficacy biological profile: ocrrelation of the biological markers with the clinical response

  • Correlation of the profile of biological markers with the clinical response (-1 and 1).

  12 months

Study Arms (2)

Thawed allogeneic WJ-MSCs

EXPERIMENTAL

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

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

Expanding allogeneic WJ-MSCs

EXPERIMENTAL

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

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

Interventions

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle: lead
• Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud - IDCBIS: collaborator

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific technical director of the Center for advanced therapies Fundación Oftalmológica de Santander (FOSCAL)

Model Details: Experimental (pilot clinical study), randomized, blind, and parallel.

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: March 12, 2024
• Study Start: June 1, 2024
• Primary Completion: June 1, 2025
• Study Completion: August 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share