Graft vs Host Disease
Conditions
Keywords
Allogeneic hematopoietic stem cell transplantation, Graft vs host disease, Regulatory T cells
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
Interventions
BIOLOGICALDonor regulatory T cell adoptive immunotherapy in chronic graft versus host disease
Regulatory T cells selected by a sequential 2 step procedure: 1. \- Negative selection of CD8 and CD19 cells 2. \- Positive selection of CD25 cells
Sponsors
Hospital de Santa Maria, Portugal
IPOFG Lisboa, Portugal
IPOFG Porto, Portugal
Instituto de Medicina Molecular João Lobo Antunes
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Response evaluated 12 weeks after infusion | Progression of graft versus host disease and myelosuppression are indicators of toxicity and MTD associated with the infusion of donor regulatory T cells |
Secondary
| Measure | Time frame |
|---|---|
| Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells | Response evaluated 12 weeks after infusion |
| 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 | Response evaluated 12 weeks after infusion |
| Survival at 1 year after administration of donor regulatory T cells in patients with chronic graft versus host disease | Response evaluated 12 months after infusion |
Countries
Portugal
Outcome results
None listed