This is a Simon's optimal two-stage phase II trial designed to estimate grade II-IV acute graft-versus-host disease (GVHD) after infusion of T regulatory (nTreg) in a fixed dose ratio to the combined CD3+ cell count of the two graft units in recipients of double UCB transplantation. The nTreg cells (manufactured from a 3rd cord blood unit) are infused on day 0 at least 1 hour after the 2nd unit of the double umbilical cord blood (UCB) transplant. The nTreg cells require an 18 day (±2 days) lead time based on the planned transplant day. The combined CD3+ cell content from the two graft UCB units is enumerated upon thaw (day 0). The patient then receives the number of nTregs cells from the 3rd cord product to achieve a Treg:CD3+ cells ratio of 5:1. The nTreg cell dose depends on the CD3+ cell content of the two graft UCB graft units, but it will not exceed the highest dose level safely tested in the ongoing University of Minnesota phase I Treg dose escalation study MT 2006-01.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Fixed dose of nTreg cells will be infused on day 0 of transplant after the umbilical cord blood cells
Fludarabine 30mg/m\^2 IV over 1 hour on days -6 through -2 from transplant
Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 from transplant
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, United States
Incidence of grade II-IV acute graft-versus-host disease
Determine if 3:1 ratio of Treg:CD3+ cells reduces the risk grade II-IV acute graft versus host disease of 20% by day 100 as compared to patients with hematological malignancy receiving same conditioning regimen and immunosuppression but no Tregs.
Time frame: Day +100
Incidence of double and single unit chimerism
Compare the incidence of double and single unit chimerism at day +100 between Treg and controls
Time frame: Day +100
Incidence of grade III-IV acute graft-versus-host disease
Compare the incidence of grade III-IV aGVHD between Treg and controls
Time frame: Day +100
Incidence of viral and fungal infections
Compare the incidence of viral and fungal infections at 1 year between Treg and controls
Time frame: 1 year
Survival
Compare the probability of survival at 1 year between Treg and controls
Time frame: 1 year
Incidence of neutrophil recovery
Compare the incidence of neutrophil recovery at day 42 between Treg and controls
Time frame: Day 42
Incidence of treatment related mortality
Determine the incidence of treatment related mortality (TRM) at 6 months between Treg and controls
Time frame: 6 months
Incidence of platelet recovery
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Total Body Irradiation (TBI) 200 cGy administered on day -1 in a single fraction will be given at a dose rate of 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Compare the incidence of platelet recovery at 1 year between Treg and controls
Time frame: 1 year
Incidence of chronic GVHD
Compare the incidence of chronic GVHD at 1 year between Treg and controls
Time frame: 1 year
Incidence of relapse
Compare the incidence of relapse at 1 year between Treg and controls
Time frame: 1 year