NCT01163201

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

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Hematologic Malignancy
• Acute Myeloid Leukemia
• Acute Lymphocytic Leukemia
• Chronic Myelogenous Leukemia in Blast Crisis
• Anemia, Refractory, With Excess of Blasts
• Chronic Myeloproliferative Disease
• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma
• Marginal Zone B-cell Lymphoma
• Follicular Lymphoma
• Lymphoplasmacytic Lymphoma
• Mantle-Cell Lymphoma
• Prolymphocytic Lymphoma
• Large Cell Non-Hodgkin's Lymphoma
• Lymphoblastic Lymphoma
• Burkitt's Lymphoma
• High Grade Non-Hodgkin's Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Treg cells	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)
BIOLOGICAL	CD3+ Teff 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
DRUG	Fludarabine	Given intravenously on Days -8 through -6, 25 mg/m\^2 over 1 hour
DRUG	Cyclophosphamide	Given intravenously on Day -7 and -6, 60 mg/kg
RADIATION	Total body irradiation	Given on Days -4 through -2, 165 cGY twice a day.
BIOLOGICAL	Umbilical cord blood transplantation	Infusion given on day 0

Timeline

• Start date: 2014-01-01
• Primary completion: 2015-01-01
• Completion: 2015-01-01
• First posted: 2010-07-15
• Last updated: 2017-12-02

Locations

1 site across 1 country: United States