Umbilical Cord Blood Transplant With Co-Infusion of T Regulatory Cells
- Determine the maximum tolerated dose of umbilical cord blood (UCB)-derived CD4- and
CD25-positive T-regulatory (Treg) cell infusion followed by double unrelated donor UCB
transplantation in patients with high-risk leukemia or other hematologic diseases.
- Determine the speed of neutrophil and platelet recovery at day 42 in these patients.
- Determine the incidence of "double chimerism" (e.g., engraftment of both UCB units) at
day 21 in these patients.
- Determine the risk of severe grade III-IV acute graft-versus-host disease (GVHD) at day
100 in these patients.
- Determine the risk of chronic GVHD at 1 year post transplantation in these patients.
- Determine the probability of survival at 100 days and 1 year post transplantation in
OUTLINE: This is an open-label, dose-escalation study of CD4- and CD25-positive umbilical
cord blood (UCB)-derived T-regulatory cells (Treg).
- Preparative therapy: Patients receive fludarabine phosphate intravenously (IV) over 1
hour on days -9 to -7 and cyclophosphamide IV over 2 hours on days -8 and -7 (1 hour
after fludarabine infusion). Patients then undergo total-body irradiation (TBI) twice
daily on days -5 to -2.
- UCB-derived Treg infusion: Patients receive UCB-derived Treg cells IV on day -1.
- Double unrelated donor UCB transplantation: Patients undergo double unrelated donor UCB
transplantation by IV infusion on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
hours or orally 2 or 3 times daily beginning on day -3 and continuing until day 100,
followed by a taper to day 180, in the absence of GVHD. Patients also receive
mycophenolate mofetil (MMF) orally or IV twice daily on days -3 to 30 or 7 days after
engraftment, whichever is later, in the absence of acute GVHD*. If no donor engraftment
occurs, MMF may be continued at the discretion of the attending physician.
NOTE: *If the patient has acute GVHD requiring systemic therapy, MMF may be stopped 7 days
after GVHD is controlled (e.g., resolution of skin rash, vomiting, and diarrhea).
Cohorts of 3-6 patients receive escalating doses of UCB-derived Treg cells until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience nonhematologic dose-limiting toxicity within 48 hours of
Treg cell infusion. At least 6 patients are treated at the MTD.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of T-regulatory cells
Dose limiting toxicities (DLT) are defined as any grade 3-4 toxicity within 24 hours of Treg cell infusion, excluding hematological .
Within 24 Hours
Claudio G. Brunstein, MD, PhD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
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