Graft vs Host Disease, Mesenchymal Stem Cell Transplantation
Conditions
Keywords
Advanced Therapy Medicinal Products, Security, Adverse events
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALMesenchymal Stem Cell Infusion
Administration of Advanced Therapy Medicinal Product in patients with chronic GVHD
Sponsors
Pontifícia Universidade Católica do Paraná
Hospital Erasto Gaertner
Hospital de Clínicas da Universidade Federal do Paraná, Brazil
Hospital Nossa Senhora das Graças
Financiadora de Estudos e Projetos
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a prospective, single-arm, open-label, phase I clinical study. Twenty patients with chronic corticosteroid-refractory graft-versus-host disease will receive 1 to 3 intravenous infusions of 2 × 10⁶/kg at 7 day intervals-the number of infusions will depend on the escalation level to which the participant was allocated. Patient follow-up will be at 12 months after the last dose of MesenCell. The infusion will be performed in conjunction with standard treatment with corticosteroids (1 mg/kg of body weight per day) and cyclosporine.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age from 18 to 70 years; * Male or female sex; * Patients after allogeneic hematopoietic stem cell transplantation (any donor or stem cell source); * Presenting with moderate or severe chronic Graft versus host Disease refractory to treatment with corticosteroids and calcineurin inhibitors; * Patients who agree to participate in this study and who sign the Informed Consent Form.
Exclusion criteria
* Patients with any concomitant clinical condition that, in the physician's opinion, contraindicates the infusion of bone marrow-containing stem cells; * Pregnancy; * Patients (or their legal guardians) who do not agree to participate in this study or who do not sign the Informed Consent Form; * Patients with recurrent malignant neoplasm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Related Adverse Events | 30 days after the last MesenCell infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Treatment Response Rate | 6 months after treatment initiation | 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. |
| Change in Overall Response | From baseline through 12 months after treatment initiation | 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. |
| Change in Organ-Specific Response Scores | From baseline through 12 months after treatment initiation | 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. |
| All-cause mortality | From the first MesenCell infusion through 12 months after the last MesenCell infusion | 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. |
| Failure-Free Survival | From the first MesenCell infusion through 12 months after the last MesenCell infusion | 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. |
| Reduction in Corticosteroid Therapy | From treatment initiation through 12 months after the last MesenCell infusion | 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. |
| Discontinuation of Immunosuppressive Therapy | From treatment initiation through 12 months after the last MesenCell infusion | 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 to Best Overall Response | From the first MesenCell infusion through 12 months after the last MesenCell infusion | 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. |
Countries
Brazil
Contacts
CONTACTCarmen L K Rebelatto, PhD
CONTACTLidiane M. B. Leite, PhD
PRINCIPAL_INVESTIGATORCarmen L K Rebelatto, PhD
Pontifícia Universidade Católica do Paraná
Outcome results
None listed