Clinical trial NCT03683498: Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-host-Disease
Official title: A Phase I 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: COMPLETED
Phase: PHASE1
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: 2018-09-25
Enrollment: 16
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Initial enrollment will be at Dose-level A. Subsequent cohorts will be dose escalated.
Primary purpose: TREATMENT

Brief summary: A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in patients who do not obtain complete remission with ruxolitinib

Detailed description: The study design is based on a phase I trial in Spanish.

A number of 16 patients will be included to assess the safety and maximum tolerated dose-level of donor regulatory enriched T cell (Treg) in steroid-refractory chronic graft versus host disease (cGVHD) patients who did not obtain complete remission under treatment with ruxolitinib.

Eligibility criteria: Inclusion Criteria:

* Recipient of allogeneic hematopoietic stem cell transplantation.
* Participants must have steroid-refractory cGVHD and had obtained a partial response after at least 4 weeks of treatment with ruxolitinib.
* Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) 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 enrolment
* No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4weeks prior to enrolment. 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 (ECOG) 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 thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
* New immunosuppressive medication in the 4 weeks prior.
* Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior.
* Post-transplant exposure to T-cell or Interleukin-2 targeted medication (e.g. alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior.
* Donor lymphocyte infusion within 100 days prior.
* Active malignant relapse.
* Active uncontrolled infection.
* Organ transplant (allograft) recipient.
* HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic hematopoietic stem cell transplant (HSCT). In addition, these individuals are at increased risk of lethal infections. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
* 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 (HSCT).
* Other investigational drugs within 4 weeks prior to enrolment, unless cleared by the Principal Investigator.
* Pregnant women are excluded from this study.

Primary outcomes:
measure: Toxicity and maximum tolerated dose
timeFrame: Up 12 weeks after infusion
Secondary outcomes:
measure: Quantification of targeted cells of manufacturing Treg-enriched product meeting the targeted cell dose-level.
timeFrame: Before 24 hours to infusion up infusion day
measure: Clinical response of Treg-enriched infusion
timeFrame: Up 12 weeks after Treg infusion
measure: Immunologic effects through phenotypical evaluation
timeFrame: Up 12 weeks after Treg infusion
measure: Immunologic effects through immune globulins.
timeFrame: Up 12 weeks after Treg infusion
measure: Immunologic effects through plasma banking
timeFrame: Up 12 weeks after Treg infusion
measure: Immunologic effects through additional mononuclear cells.
timeFrame: Up 12 weeks after Treg infusion
measure: Survival after one year of Treg infusion
timeFrame: 1 year after Treg infusion
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
state: Seville
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: