The purpose of this Phase I clinical trial is to evaluate the safety and potential treatment response of bone marrow-derived mesenchymal stem cells (MesenCell) in adult patients with moderate or severe chronic graft-versus-host disease (cGVHD) that is refractory to corticosteroid treatment. The main questions it seeks to answer are: * Is MesenCell infusion safe in patients with corticosteroid-refractory chronic graft-versus-host disease? * Can MesenCell treatment improve the clinical response and disease control in these patients? Participants will receive one to three intravenous infusions of MesenCell, according to the study protocol and be followed for 12 months after the last MesenCell infusion.
This is a prospective, single-arm, open-label Phase I clinical trial designed to evaluate the safety and treatment response of bone marrow-derived mesenchymal stem cells (MesenCell) in adult patients with moderate or severe chronic graft-versus-host disease (cGVHD) refractory to corticosteroid treatment. Approximately 20 participants will be enrolled in the study. Participants will receive one to three intravenous infusions of MesenCell at a dose of 2 × 10⁶ cells/kg, administered at seven-day intervals. The number of infusions will depend on the dose-escalation level to which each participant is assigned. MesenCell will be administered in combination with standard treatment consisting of corticosteroids at a dose of 1 mg/kg/day and cyclosporine. Participants will undergo clinical and laboratory monitoring throughout the study to evaluate the safety of the intervention and the occurrence, frequency, severity, and causal relationship of adverse events following MesenCell infusion. Treatment response will be assessed using standardized criteria for chronic graft-versus-host disease, including overall and organ-specific response. The study will also evaluate all-cause mortality, failure-free survival, and changes in corticosteroid and immunosuppressive medication use, including dose reductions, treatment discontinuation, and reduction in the number of immunosuppressive agents. Participants will be followed for 12 months after administration of the last MesenCell dose. During this period, clinical assessments and review of medical records will be performed to monitor treatment response, disease progression, safety outcomes, need for additional systemic therapy, mortality, and changes in concomitant immunosuppressive treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Administration of Advanced Therapy Medicinal Product in patients with chronic GVHD
Hospital de Clínicas da Universidade Federal do Paraná
Curitiba, Paraná, Brazil
Pontifícia Universidade Católica do Paraná
Curitiba, Paraná, Brazil
Hospital Nossa Senhora das Graças
Curitiba, Paraná, Brazil
Hospital Erasto Gaertner
Curitiba, Paraná, Brazil
Number of Participants With Treatment-Related Adverse Events
Number of participants experiencing unexpected adverse events or adverse events considered probably or definitely attributable to MesenCell infusion within 30 days after the last dose. Adverse events will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 (2025). Grade 3 or higher events will be considered for toxicity assessment.
Time frame: 30 days after the last MesenCell infusion
Overall Treatment Response Rate
Percentage of participants with partial or complete overall response, according to the 2014 National Institutes of Health (NIH) Consensus Development Project response criteria for chronic graft-versus-host disease.
Time frame: 6 months after treatment initiation
Change in Overall Response
Change from baseline in overall severity according to the 2014 National Institutes of Health (NIH) Consensus Development Project criteria. Overall severity is classified as mild, moderate, or severe based on the number of organs involved and the severity scores assigned to each affected organ. Mild disease is defined as involvement of 1 or 2 organs, with no organ scoring more than 1, and a lung score of 0. Moderate disease is defined as involvement of 3 or more organs with no organ scoring more than 1, or at least 1 non-lung organ with a score of 2, or a lung score of 1. Severe disease is defined as at least 1 organ with a score of 3 or a lung score of 2 or 3.
Time frame: From baseline through 12 months after treatment initiation
Change in Organ-Specific Response Scores
Change from baseline in organ-specific response scores for the skin, mouth, eyes, gastrointestinal tract, liver, lungs, joints and fascia, and genital tract. Each organ is scored on an ordinal scale from 0 to 3 according to predefined clinical or laboratory criteria specific to the affected organ. A score of 0 indicates no signs or symptoms, while a score of 3 indicates severe involvement. Higher scores indicate greater disease severity and a worse outcome.
Time frame: From baseline through 12 months after treatment initiation
All-cause mortality
Time from the first MesenCell infusion to death from any cause. Survival will be estimated at 6 and 12 months and as median overall survival during the follow-up period. Participants who remain alive will be censored at the last contact.
Time frame: From the first MesenCell infusion through 12 months after the last MesenCell infusion
Failure-Free Survival
Time from the first MesenCell infusion to the first occurrence of treatment failure, defined as relapse of the underlying disease, progression or reactivation of chronic graft-versus-host disease, or death from any cause. Relapse of the underlying disease will be assessed primarily by complete blood count, with bone marrow aspirate performed when relapse is suspected based on blood count findings. Reactivation of chronic graft-versus-host disease will be assessed at each medical visit according to the NIH organ scoring criteria. Participants without treatment failure will be censored at the last contact. Failure-free survival will be estimated at 6 and 12 months.
Time frame: From the first MesenCell infusion through 12 months after the last MesenCell infusion
Reduction in Corticosteroid Therapy
Percentage of participants who have a reduction in corticosteroid dose compared with baseline during the follow-up period. Corticosteroid dose will be assessed using medical records, prescription data, and clinical follow-up.
Time frame: From treatment initiation through 12 months after the last MesenCell infusion
Discontinuation of Immunosuppressive Therapy
Percentage of participants who discontinue systemic immunosuppressive therapy during the follow-up period. Immunosuppressive therapy use and discontinuation will be determined from medical records, prescription data, and clinical follow-up.
Time frame: From treatment initiation through 12 months after the last MesenCell infusion
Time to Best Overall Response
Time from the first MesenCell infusion to the first documentation of the best overall response according to the 2014 National Institutes of Health (NIH) Consensus Development Project response criteria for chronic graft-versus-host disease.
Time frame: From the first MesenCell infusion through 12 months after the last MesenCell infusion
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.