Chronic Graft vs Host Disease Clinical Trial
— Treg4GVHDOfficial title:
Phase II Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in Patients Who do Not Obtain Complete Remission With Ruxolitinib
Phase II clinical trial to assess the efficacy of donor regulatory enriched T cells in steroid-refractory chronic graft versus host disease patients who did not obtain complete remission under treatment with ruxolitinib
Status | Recruiting |
Enrollment | 15 |
Est. completion date | February 15, 2026 |
Est. primary completion date | August 15, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility | Inclusion Criteria: - Recipient of allogeneic hematopoietic stem cell transplantation - Participants must have steroid-refractory cGVHD and had obtained any response other than progression after at least 12 weeks of treatment with ruxolitinib. Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at = 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms. - Stable dose of glucocorticoids for 4 weeks prior to enrollment. - No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug. - No age limit. In the case of children participating in the study, the informed consent will be signed by a parents or legal guardians. - Eastern Cooperative Oncology Group scale performance status 0-2 - Participants must have adequate organ function - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Ongoing prednisone requirement >1 mg/kg/day (or equivalent). - Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable). - History of active thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura in the last 6 months. - New immunosuppressive medication in the 4 weeks prior to enrollment. - Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior to enrollment. - Post-transplant exposure to T-cell or interleukin-2 targeted medication within 100 days prior to enrollment. - Donor lymphocyte infusion within 100 days prior to enrollment. - Active malignant relapse. - Active uncontrolled infection. - Organ transplant (allograft) recipient. - HIV-positive individuals on combination antiretroviral therapy are ineligible. - Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after hematopoietic stem cell transplant. - Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the Principal Investigator. - Pregnant women are excluded from this study. |
Country | Name | City | State |
---|---|---|---|
Spain | José Antonio Pérez Simón | Sevilla |
Lead Sponsor | Collaborator |
---|---|
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla |
Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants with overall response rate. | Obtain =65% the overall response rate at 6 months after infusion | 6 months post-infusion | |
Primary | Number of Participants with overall response rate. | Obtain =75% the overall response rate at 1 year after infusion | 1 year post-infusion | |
Primary | Survival | Number of patients who survive after Regulatory T-cell enriched infusion | 1 year after Regulatory T-cell enriched infusion | |
Secondary | Disease evaluation through Symptoms of the disease | Symptoms of the disease through chronic graft-versus-host disease activity assessment (clinician) according to NIH consensus- form A | Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion | |
Secondary | Disease evaluation through measurement of quality of life | Measurement of quality of life through Functional Assessment of Cancer Therapy - Bone Marrow Transplantation | Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion | |
Secondary | Disease evaluation through Symptoms of the disease | Symptoms of the disease through chronic graft-versus-host disease symptom scoring scale | Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion | |
Secondary | Immunosuppressive requirements. | Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication | Screening, month1, months 3, 6, and 12 after infusion | |
Secondary | Free survival | To evaluate failure free survival (change of immunosuppression, mortality or relapse) | 1 year after infusion. | |
Secondary | Immunologic monitoring and in vivo Treg tracking through immune globulins | Quantitative immune globulins | 1 year after infusion and after infusion | |
Secondary | Immunologic monitoring and in vivo Treg tracking through plasma | Plasma banking | 1 year after infusion and after infusion | |
Secondary | Immunologic monitoring and in vivo Treg tracking through mononuclear cells | Storage of additional mononuclear cells | 1 year after infusion and after infusion | |
Secondary | Immunologic monitoring and in vivo Treg tracking through lymphocyte | Detailed immunological evaluation of lymphocyte | 1 year after infusion and after infusion | |
Secondary | Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets | Quantitative Natural Killer cell subsets | 1 year after infusion and after infusion | |
Secondary | Purity of Treg-enriched cell infusion | Percentage of cells viability, negative gram stain/endotoxin, percentage of cluster of differentiation 4+ cluster of differentiation 25+ cells and cluster of differentiation 4+cluster of differentiation25+cluster of differentiation127- Treg in order to consider for the infusion. | Before 24 hours to infusion up infusion day | |
Secondary | Toxicity monitoring of Treg-enriched cells | Number of grade 3 or higher Adverse Events and all Serious Adverse Events according to the Version 5.0 of the NCI Common Terminology Criteria for Adverse Events. | Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion | |
Secondary | Life-threatening infections | Number of infections | Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion | |
Secondary | Predictors of clinical response | Quantify predictors of clinical response among patients receiving ruxolitinib | 1 year after infusion |
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