Chronic Graft vs Host Disease
Conditions
Keywords
Ruxolitinib, T cells
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.
Interventions
BIOLOGICALRegulatory 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.
Sponsors
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The doses of Treg-enriched cells will be 2x10\^6 cells/kg
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with overall response rate. | 6 months post-infusion | Obtain ≥65% the overall response rate at 6 months after infusion |
| Survival | 1 year after Regulatory T-cell enriched infusion | Number of patients who survive after Regulatory T-cell enriched infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunosuppressive requirements. | Screening, month1, months 3, 6, and 12 after infusion | Evaluation of needs of additional permitted immunosuppressive treatment administered as concomitant medication |
| 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 immune globulins | 1 year after infusion and after infusion | Quantitative immune globulins |
| 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 mononuclear cells | 1 year after infusion and after infusion | Storage of additional mononuclear cells |
| 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 activity assessment (clinician) according to NIH consensus- form A |
| Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets | 1 year after infusion and after infusion | Quantitative Natural Killer cell subsets |
| 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. |
| 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. |
| 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 |
| Immunologic monitoring and in vivo Treg tracking through lymphocyte | 1 year after infusion and after infusion | Detailed immunological evaluation of lymphocyte |
| 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 |
Countries
Spain
Contacts
Primary ContactJosé Antonio Pérez-Simón, M.D. Ph.D
Backup ContactClara M. Rosso, M.D. Ph.D
Outcome results
None listed