donor regulatory t-cells for cgvhd in patients who do not obtain complete remission with ruxolitinib

Conditions: Chronic Graft vs Host Disease

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

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.

Eligibility criteria:
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.

Keywords: ruxolitinib t cells