Clinical Trial: A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1/2 Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease

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 Summary:

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

Sponsor: Instituto de Medicina Molecular

Current Primary Outcome: 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 [ Time Frame: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Chronic graft versus host disease improvement according to the 2014 NIH consensus criteria following the infusion of donor regulatory T cells [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Response evaluated 12 months after infusion ]


Original Secondary Outcome: Same as current

Information By: Instituto de Medicina Molecular

Dates:
Date Received: March 1, 2015
Date Started: March 2015
Date Completion: December 2019
Last Updated: March 6, 2016
Last Verified: March 2016