Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation
- To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely
administered to patients undergoing HLA-identical sibling donor Peripheral Blood
Progenitor Cell (PBPC) transplantation.
- To determine whether CD4+ and CD25+ cells can be safely administered to patients with
high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC
- To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD),
chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T
cells in these patients.
OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed
by a phase II study. All patients receive myeloablative preparative therapy and GVHD
prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10.
- First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive
unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over
15-60 minutes at the assigned dose on day -2.
- Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC
transplantation IV on day 0.
Patients undergo blood sample collection prior to commencement of preparative therapy and
then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for
immune reconstitution by immunophenotyping and functional analyses.
After completion of study therapy, patients are followed for up to 1 year.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
Day 0 (48 hours post infusion)
Margaret L. MacMillan, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center, University of Minnesota||Minneapolis, Minnesota 55455|