Clinical trial NCT02385019: A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease
Official title: A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Graft vs Host Disease
Keywords: Allogeneic hematopoietic stem cell transplantation
Graft vs host disease
Regulatory T cells
Lead sponsor: Instituto de Medicina Molecular João Lobo Antunes
Sponsor class: OTHER
Collaborators: name: Hospital de Santa Maria, Portugal
name: IPOFG Lisboa, Portugal
name: IPOFG Porto, Portugal
First posted: 2015-03-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 1/2 clinical study for the treatment of steroid-refractory chronic graft versus host disease after an allogeneic transplant of hematopoietic progenitors with donor CliniMACS-selected regulatory T cells

Detailed description: Phase 1/2 clinical study evaluating safety (Phase 1) and preliminary efficacy (Phase 2) of donor regulatory T cells for patients with steroid-refractory chronic graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).

Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs.

Phase 1 clinical trial will include groups of 5 patients sequentially treated with: 0.5 x 10ˆ6, 1.0 x 10ˆ6, 2-3 x 10ˆ6 donor Treg/kg. Phase 2 clinical trial will include another 5 to 10 patients treated with MTD.

Donor Treg will be selected by the following sequential steps:

1. - negative depletion of CD8 and CD19 cells
2. - positive selection of CD25 cells

Eligibility criteria: Inclusion Criteria:

1. Patients must have persistent signs and symptoms despite the use of prednisone or equivalent at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day), for at least 4 weeks without complete resolution of signs and symptoms. Occasional patients requiring lower doses of prednisone will be eligible if associated with other immunosuppressive drugs.
2. Stable immunosuppressive medication in the 4 weeks prior to initiation of treatment
3. PS 0-2 ECOG
4. Adequate liver, kidney, lung and hematopoietic system functions

Exclusion Criteria:

1. Pediatric patients
2. Pregnant women
3. Ongoing prednisone requirement \>1 mg/kg/day (or equivalent)
4. Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)
5. New immunosuppressive medication in the 4 weeks prior
6. Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior
7. Exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior
8. Donor lymphocyte infusion within 100 days prior
9. Active malignant relapse
10. Active uncontrolled infection
11. HIV-infected patients

Primary outcomes:
measure: Progression of graft versus host disease according to the 2014 NIH consensus criteria and myelosuppression after the administration of 3 doses of donor regulatory T cells / kg recipient's body weight: 0.5 x 10ˆ6, 1.0 x 10ˆ6 and 2.0-3.0 x 10ˆ6 cells
timeFrame: Response evaluated 12 weeks after infusion
Secondary outcomes:
measure: Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells
timeFrame: Response evaluated 12 weeks after infusion
measure: Total lymphocyte, CD4, CD8 and regulatory T cell counts after the infusion of donor regulatory T cells for the treatment of chronic graft versus host disease
timeFrame: Response evaluated 12 weeks after infusion
measure: Survival at 1 year after administration of donor regulatory T cells in patients with chronic graft versus host disease
timeFrame: Response evaluated 12 months after infusion
Other outcomes:
Locations:
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria, Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia
Study officials:
References: