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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05095649
Other study ID # Treg4GVHD
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date March 24, 2022
Est. completion date February 15, 2026

Study information

Verified date March 2024
Source Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Contact José Antonio Pérez-Simón, M.D. Ph.D
Phone 955013414
Email josea.perez.simon.sspa@juntadeandalucia.es
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


Description:

A number of 15 patients will be included 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 after 12 weeks of treatment with ruxolitinib. The doses of Treg-enriched cells will be 2x10^6 cells/kg. Survival at 1 year after Treg infusion will be represented based on the clinical data with Kaplan Meier curves.


Recruitment information / eligibility

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.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Regulatory T-cell enriched infusion
Enrichment of cluster of differentiation 25hi regulatory T cells from cluster of differentiation antigen 8 and/or cluster of differentiation antigen19 pre-depleted leukapheresis products.

Locations

Country Name City State
Spain José Antonio Pérez Simón Sevilla

Sponsors (1)

Lead Sponsor Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Country where clinical trial is conducted

Spain, 

Outcome

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
See also
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Completed NCT01221766 - Impact of Adnexal Involvement of the Severity and Prognosis of Chronic Graft-versus-Host Disease N/A
Active, not recruiting NCT02067832 - Predictive Biomarkers For Pediatric Chronic Graft-Versus-Host Disease
Active, not recruiting NCT02759731 - Study of Baricitinib, a JAK1/2 Inhibitor, in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Phase 1/Phase 2
Terminated NCT04852692 - A Study to Investigate the Comparative Effectiveness of Ibrutinib in Steroid Dependent/Refractory cGVHD Participants
Recruiting NCT02669251 - Alvelestat (MPH966), an Oral Neutrophil Elastase Inhibitor, in Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation Phase 1/Phase 2