Donor Regulatory T-cells for cGVHD in Patients Who do Not Obtain Complete Remission With Ruxolitinib
- Conditions
- Chronic Graft vs Host Disease
- Interventions
- Biological: Regulatory T-cell enriched infusion
- Registration Number
- NCT05095649
- Brief 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
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Regulatory T-cell enriched infusion Regulatory T-cell enriched infusion The doses of Regulatory T-cell enriched infusion will be 2x10\^6 cells/kg
- Primary Outcome Measures
Name Time Method Survival 1 year after Regulatory T-cell enriched infusion Number of patients who survive after Regulatory T-cell enriched infusion
Number of Participants with overall response rate. 1 year post-infusion Obtain ≥75% the overall response rate at 1 year after infusion
- Secondary Outcome Measures
Name Time Method Immunologic monitoring and in vivo Treg tracking through lymphocyte 1 year after infusion and after infusion Detailed immunological evaluation of lymphocyte
Purity of Treg-enriched cell infusion Before 24 hours to infusion up infusion day 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.
Immunologic monitoring and in vivo Treg tracking through immune globulins 1 year after infusion and after infusion Quantitative immune globulins
Toxicity monitoring of Treg-enriched cells Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion 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.
Disease evaluation through Symptoms of the disease Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion Symptoms of the disease through chronic graft-versus-host disease symptom scoring scale
Disease evaluation through measurement of quality of life Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion Measurement of quality of life through Functional Assessment of Cancer Therapy - Bone Marrow Transplantation
Free survival 1 year after infusion. To evaluate failure free survival (change of immunosuppression, mortality or relapse)
Immunologic monitoring and in vivo Treg tracking through mononuclear cells 1 year after infusion and after infusion Storage of additional mononuclear cells
Immunosuppressive requirements. Screening, month1, months 3, 6, and 12 after infusion Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication
Immunologic monitoring and in vivo Treg tracking through plasma 1 year after infusion and after infusion Plasma banking
Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets 1 year after infusion and after infusion Quantitative Natural Killer cell subsets
Life-threatening infections Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion Number of infections
Predictors of clinical response 1 year after infusion Quantify predictors of clinical response among patients receiving ruxolitinib
Trial Locations
- Locations (1)
José Antonio Pérez Simón
🇪🇸Sevilla, Spain