T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01163201|
Recruitment Status : Withdrawn (Replaced by a new study)
First Posted : July 15, 2010
Last Update Posted : December 2, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|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||Biological: Treg cells Biological: CD3+ Teff cells Drug: Fludarabine Drug: Cyclophosphamide Radiation: Total body irradiation Biological: Umbilical cord blood transplantation||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Optimization of the T Regulatory Cell and T Effector Cell Doses in Recipients of Double UCB Transplantation for Treatment of Hematological Malignancies|
|Study Start Date :||January 2014|
|Estimated Primary Completion Date :||January 2015|
|Estimated Study Completion Date :||January 2015|
Experimental: Treg Plus CD3+Teff Treatment
Includes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation
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
Given intravenously on Days -8 through -6, 25 mg/m^2 over 1 hour
Other Name: Fludara
Given intravenously on Day -7 and -6, 60 mg/kg
Other Name: Cytoxan
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
Other Name: UCBT
- Optimal Cell Dose Mixture [ Time Frame: Day 0 ]Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD
- Determine incidence of infusional toxicity [ Time Frame: 48 hours ]reaction that occurs with 48 hours of product infusion
- Incidence of neutrophil recovery [ Time Frame: Day 42 ]Determine the incidence of neutrophil recovery (absolute neutrophil count ≥ 500/uL) at day 42
- Incidence of double and single chimerism [ Time Frame: Day +21, Day +180, 1 Year ]Determine incidence of double and single unit chimerism at various time points
- Incidence of Viral and Fungal Infections [ Time Frame: 1 Year ]Determine incidence of viral and fungal infections at 1 year
- 1 Year Survival [ Time Frame: 1 Year ]Estimate the probability of survival at 1 year
- Incidence of Grade III-IV Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ]Determine the incidence of grade III-IV acute GVHD at day 100
- Incidence of Treatment Related Death [ Time Frame: 6 Months ]Determine the incidence of treatment related mortality (TRM) at 6 months
- Incidence of Platelet Recovery [ Time Frame: 1 Year ]Determine the incidence of platelet recovery (platelet count ≥ 50,000/uL) at 1 year
- Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: 1 Year ]Determine the incidence of chronic GVHD at 1 year
- Incidence of Relapse [ Time Frame: 1 Year ]Determine the incidence of relapse at 1 year
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01163201
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55445|
|Principal Investigator:||Claudio Brunstein, MD, PhD||Masonic Cancer Center, University of Minnesota|