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Includes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation

Given by infusion on Day 0 after transplantation - Five doses of Treg (3 x 10\^6/kg, 10 x 10\^6/kg, 30 x 10\^6/kg, 100 x 10\^6/kg and 300 x 10\^6/kg)

Treg cells

Given by infusion on Day 0 after transplantation - 5 doses of CD3+ Teff cells (3 x 10\^6 cells/kg, 6 x 10\^6 cells/kg, 9 x 10\^6 cells/kg, 12 x 10\^6 cells/kg, and 15 x 10\^6 cells/kg with the latter dose representing the median number of CD3+ cells in two UCB unit grafts

CD3+ Teff cells

Given intravenously on Days -8 through -6, 25 mg/m\^2 over 1 hour

Given intravenously on Day -7 and -6, 60 mg/kg

Given on Days -4 through -2, 165 cGY twice a day.

Total body irradiation

Umbilical cord blood transplantation

Claudio Brunstein, MD, PhD

This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB) Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible without conferring grade II-IV acute graft-versus-host disease (GVHD).

In this study, the investigators propose to add UCB Treg and UCB CD3+ Teff cells to the two TCD UCB donor units with the goal of transplanting as many CD3+ Teff cells as possible without reintroducing risk of acute GVHD. The investigators hypothesize that Treg will permit the reintroduction of CD3+ Teff cells that will provide a bridge while awaiting HSC T cell recovery long term. The co-infusion of Treg will prevent GVHD without the need for prolonged pharmacologic immunosuppression.

Based on prior studies, the first patient will start at lowest dose combination (3 x 10\^6/kg of Treg and 3 x 10\^6/kg of CD3+ Teff cells).

One patient will be entered at each level with a minimum of 35 days to observe the patient prior to moving to the next dose level. (1) If GVHD does not occur, a "successful step", then the CD3+ Teff cell dose will increase to the next higher level for the next patient; (2) If GVHD occurs, a "failed step", then Treg dose will increase to the next higher level for the next patient. It would take a minimum of 5 (if no GVHD) and maximum of 9 patients (if GVHD is observed at each level) to complete all Treg:CD3+ Teff cell combinations.

An additional 10 patients will be enrolled to verify that this reflects the optimal combination and evaluate its safety profile.

T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies

Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD

reaction that occurs with 48 hours of product infusion

Determine the incidence of neutrophil recovery (absolute neutrophil count ≥ 500/uL) at day 42

Determine incidence of double and single unit chimerism at various time points

Determine incidence of viral and fungal infections at 1 year

Estimate the probability of survival at 1 year

Determine the incidence of grade III-IV acute GVHD at day 100

Determine the incidence of treatment related mortality (TRM) at 6 months

Determine the incidence of platelet recovery (platelet count ≥ 50,000/uL) at 1 year

Determine the incidence of chronic GVHD at 1 year

Determine the incidence of relapse at 1 year

Masonic Cancer Center, University of Minnesota

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies	NCT01163201	Hematologic Mal... Acute Myeloid L... Acute Lymphocyt... Chronic Myeloge... Anemia, Refract... Chronic Myelopr... Chronic Lymphoc... Small Lymphocyt... Marginal Zone B... Follicular Lymp... Lymphoplasmacyt... Mantle-Cell Lym... Prolymphocytic ... Large Cell Non-... Lymphoblastic L... Burkitt's Lymph... High Grade Non-...	Treg cells CD3+ Teff cells Fludarabine Cyclophosphamid... Total body irra... Umbilical cord ...	18 Years - 55 Years	Masonic Cancer Center, University of Minnesota
T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies	NCT01163201	Hematologic Mal... Acute Myeloid L... Acute Lymphocyt... Chronic Myeloge... Anemia, Refract... Chronic Myelopr... Chronic Lymphoc... Small Lymphocyt... Marginal Zone B... Follicular Lymp... Lymphoplasmacyt... Mantle-Cell Lym... Prolymphocytic ... Large Cell Non-... Lymphoblastic L... Burkitt's Lymph... High Grade Non-...	Treg cells CD3+ Teff cells Fludarabine Cyclophosphamid... Total body irra... Umbilical cord ...	18 Years - 55 Years	Masonic Cancer Center, University of Minnesota

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