Clinical trial NCT05095649: Donor Regulatory T-cells for cGVHD in Patients Who do Not Obtain Complete Remission With Ruxolitinib
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Graft vs Host Disease
Keywords: Ruxolitinib
T cells
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2021-10-27
Enrollment: 15
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The doses of Treg-enriched cells will be 2x10\^6 cells/kg
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants with overall response rate.
timeFrame: 6 months post-infusion
measure: Number of Participants with overall response rate.
timeFrame: 1 year post-infusion
measure: Survival
timeFrame: 1 year after Regulatory T-cell enriched infusion
Secondary outcomes:
measure: Disease evaluation through Symptoms of the disease
timeFrame: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
measure: Disease evaluation through measurement of quality of life
timeFrame: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
measure: Disease evaluation through Symptoms of the disease
timeFrame: Screening, weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 months after infusion
measure: Immunosuppressive requirements.
timeFrame: Screening, month1, months 3, 6, and 12 after infusion
measure: Free survival
timeFrame: 1 year after infusion.
measure: Immunologic monitoring and in vivo Treg tracking through immune globulins
timeFrame: 1 year after infusion and after infusion
measure: Immunologic monitoring and in vivo Treg tracking through plasma
timeFrame: 1 year after infusion and after infusion
measure: Immunologic monitoring and in vivo Treg tracking through mononuclear cells
timeFrame: 1 year after infusion and after infusion
measure: Immunologic monitoring and in vivo Treg tracking through lymphocyte
timeFrame: 1 year after infusion and after infusion
measure: Immunologic monitoring and in vivo Treg tracking through Natural Killer cell subsets
timeFrame: 1 year after infusion and after infusion
measure: Purity of Treg-enriched cell infusion
timeFrame: Before 24 hours to infusion up infusion day
measure: Toxicity monitoring of Treg-enriched cells
timeFrame: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
measure: Life-threatening infections
timeFrame: Weeks 1, 2, 4, 6, 12 and months 6, 9 and 12 after infusion
measure: Predictors of clinical response
timeFrame: 1 year after infusion
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: José Antonio Pérez Simón
Study officials:
affiliation: Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla.
name: José Antonio Pérez-Simón, M.D. Ph.D
role: PRINCIPAL_INVESTIGATOR
References: