T-Regulatory Cell Infusion Post Umbilical Cord Blood Transplant in Patients With Advanced Hematologic Cancer
NCT ID: NCT00602693
Last Updated: 2017-12-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
41 participants
INTERVENTIONAL
2007-07-23
2015-04-16
Brief Summary
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PURPOSE: This phase I trial is studying the side effects and best dose of donor T-regulatory cells after an umbilical cord blood transplant in treating patients with advanced hematologic cancer or other disorder.
Detailed Description
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Primary
* Determine the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived T-regulatory (Treg) cells.
Secondary
* Estimate the proportion of patients with detectable circulating Treg cells at 0, 1, 3, 7, and 14 days after infusion.
* Estimate the risk of grades II-IV and III-IV acute graft versus host disease (GVHD) at day +100 with the infusion of Treg cells.
* Estimate the proportion of patients with sustained donor engraftment.
* Estimate the proportion of patients with double chimerism at 6 months and 1 year.
* Determine the speed and cumulative incidence of neutrophil recovery by day 42 and platelet recovery by 6 months after UCB transplantation.
* Estimate the risk of chronic GVHD at 1 year.
* Estimate the probability of disease-free survival at 100 days and 1 year.
* Estimate the risk of fungal and viral infections at 1 year
* Estimate the risk of relapse at 1 year
* Characterize the pattern of immune cell recovery over 1 year
OUTLINE: This is a dose-escalation study of umbilical cord blood (UCB)-derived T-regulatory (Treg) cells. Patients receive nonmyeloablative UCB transplantation and post-transplant immunosuppression as in protocol UMN-2005LS036 (without antithymocyte globulin during conditioning regimen).
* Nonmyeloablative conditioning and UCB transplantation: Patients receive allopurinol on days -7 to day 0, fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6; undergo total-body irradiation (TBI) once on day -1; and undergo UCB transplantation on day 0.
* Immunosuppression therapy: Beginning on day -3 and continuing until day +100, patients receive sirolimus intravenously (IV) with 8-12 mg oral loading dose followed by a single dose of 4mg/day with a target serum concentration of 3-12 mg/mL with a taper until day +180. Patients also receive mycophenolate mofetil IV or orally every 8 hours on days -3 to +30.
* Radiation therapy: total body irradiation is administered on Day -1 of 200 cGy.
* UCB Treg cell infusion: Patients receive escalating doses of UCB-derived CD4+ CD25+ Treg cells IV on day +1 (and Day +15 for dose level 5 only) until the maximum tolerated dose is obtained.
After completion of study treatment, patients are followed at day 180, 360, and 720.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
umbilical cord blood transplantation
Infusion of umbilical cord blood
Allopurinol
Administration begins Day -7 through Day 0, tablet or powder prescribed on an individual basis.
fludarabine phosphate
40 mg/m\^2 intravenously over 1 hour on Days -6, -5, -4, -3, -2
Cyclophosphamide
50 mg/kg intravenous over 2 hours on Day -6
Total body irradiation
200 cGy on Day -1
Treg infusion
Infusion of T regulatory cells on Day +1 (also Day +15 for Dose level 5 only). Dose escalation ranges include 1, 3, 10, 30, 100, 300 1000, and 300 x 10\^5 Treg/kg.
Sirolimus
Beginning on day -3 and continuing until day +100, patients receive sirolimus intravenously (IV) with 8-12 mg oral loading dose followed by a single dose of 4mg/day with a target serum concentration of 3-12 mg/mL with a taper until day +180.
Interventions
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umbilical cord blood transplantation
Infusion of umbilical cord blood
Allopurinol
Administration begins Day -7 through Day 0, tablet or powder prescribed on an individual basis.
fludarabine phosphate
40 mg/m\^2 intravenously over 1 hour on Days -6, -5, -4, -3, -2
Cyclophosphamide
50 mg/kg intravenous over 2 hours on Day -6
Total body irradiation
200 cGy on Day -1
Treg infusion
Infusion of T regulatory cells on Day +1 (also Day +15 for Dose level 5 only). Dose escalation ranges include 1, 3, 10, 30, 100, 300 1000, and 300 x 10\^5 Treg/kg.
Sirolimus
Beginning on day -3 and continuing until day +100, patients receive sirolimus intravenously (IV) with 8-12 mg oral loading dose followed by a single dose of 4mg/day with a target serum concentration of 3-12 mg/mL with a taper until day +180.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Eligible for and co-enrolled on protocol UMN-2005LS036, for treatment of any of the following advanced hematologic malignancies:
* Acute leukemias in complete remission (high risk CR1 or subsequent CR); chronic myelogenous leukemia (except refractory blast crisis); myelodysplastic syndrome with severe pancytopenia or complex cytogenetics, large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone b-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia may be eligible after initial therapy.
* Have three partially HLA matched umbilical cord blood (UCB) units (1-2 units for UCB transplantation per MT2005-02 and 1 unit for the Treg cell infusion.)
* Adequate organ function
Exclusion Criteria
* Pregnancy or breastfeeding
* Current active serious infection
* Evidence of human immunodeficiency virus (HIV) or known HIV positive serology
* Patients with acute leukemia in morphologic relapse/persistent disease defined as \>5% blasts in a \> or = 15% cellular bone marrow or any % blasts if blasts have unique morphologic markers (e.g., Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
* Chronic myelogenous leukemia in refractory blast crisis.
* Active central nervous system malignancy.
18 Years
75 Years
ALL
No
Sponsors
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Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Claudio G. Brunstein, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Margaret L. MacMillan, MD
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Countries
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References
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Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011 Jan 20;117(3):1061-70. doi: 10.1182/blood-2010-07-293795. Epub 2010 Oct 15.
Other Identifiers
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MT2006-01
Identifier Type: OTHER
Identifier Source: secondary_id
0701M00303
Identifier Type: OTHER
Identifier Source: secondary_id
2007LS022
Identifier Type: -
Identifier Source: org_study_id