T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies
NCT ID: NCT01163201
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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WITHDRAWN
PHASE1/PHASE2
INTERVENTIONAL
2014-01-31
2015-01-31
Brief Summary
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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
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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
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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
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)
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
Fludarabine
Given intravenously on Days -8 through -6, 25 mg/m\^2 over 1 hour
Cyclophosphamide
Given intravenously on Day -7 and -6, 60 mg/kg
Total body irradiation
Given on Days -4 through -2, 165 cGY twice a day.
Umbilical cord blood transplantation
Infusion given on day 0
Interventions
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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)
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
Fludarabine
Given intravenously on Days -8 through -6, 25 mg/m\^2 over 1 hour
Cyclophosphamide
Given intravenously on Day -7 and -6, 60 mg/kg
Total body irradiation
Given on Days -4 through -2, 165 cGY twice a day.
Umbilical cord blood transplantation
Infusion given on day 0
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
UCB Requirements
* Three UCB units are required - one for Treg production and two for UCB transplant. The unrelated UCB donors must be 4-6/6 HLA-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B to antigen level resolution and DR to allele level resolution). Suitable UCB units will be selected according to the University Of Minnesota UCB Graft Selection Algorithm.
* Suitable UCB units must be ABO matched.
Disease Criteria:
* Patients aged 18 to 55 years
* Acute Myeloid Leukemia: with morphologically persistent disease in a representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy (if patient refuses or is disqualified from alternative protocols), or in 3rd or higher complete remission (CR).
* Acute Lymphocytic Leukemia: with morphologically persistent disease in a representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy, or in 3rd or higher CR
* Chronic Myelogenous Leukemia in Blast Crisis: with ≤10% residual blasts in the bone marrow aspirate after at least 1 cycle of induction chemotherapy in combination with a tyrosine kinase inhibitor (TKI)
* Refractory Anemia with Excess Blasts: (≤ 10%) in representative bone marrow aspirate sample of blasts after 1 cycle of induction chemotherapy. If treated with hypomethylating agents, patients are eligible if blast count is ≤ 10% after 4 cycles or evidence of stable or progressive disease after at least 2 cycles.
* Chronic Myeloproliferative Disease
* Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma or Follicular Lymphoma: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
* Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
* Large Cell Non-Hodgkin's Lymphoma: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
* Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other High-Grade NHL: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
* Performance Status, Age, and Organ Function
* Adequate performance status defined as a Karnofsky score ≥ 80%
* Adequate organ function defined as:
* Renal: creatinine \< 2.0 mg/dL,
* Hepatic: bilirubin, AST/ALT, ALP \< 5 x upper limit of normal,
* Pulmonary function: DLCOcorr \> 50% normal,
* Cardiac: left ventricular ejection fraction \> 45%
* Voluntary written informed consent signed before performance of any study-related procedure not part of normal medical care
Exclusion Criteria
* Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
* History of HIV infection
* Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
* Prior myeloablative transplant within the last 6 months
* Extensive prior therapy including \> 12 months alkylator therapy or \> 6 months alkylator therapy with extensive radiation
* Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar) as part of their salvage therapy (not eligible for myeloablative umbilical cord blood transplant)
18 Years
55 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 Brunstein, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Countries
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Other Identifiers
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MT2009-03
Identifier Type: OTHER
Identifier Source: secondary_id
0910M73595
Identifier Type: OTHER
Identifier Source: secondary_id
2009LS018
Identifier Type: -
Identifier Source: org_study_id