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

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

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