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

Withdrawn before enrolling · Phase 1/Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT01163201
Run by: Masonic Cancer Center, University of Minnesota
People needed: 0
Starts: 2014-01-01
Expected to finish: 2015-01-01
Last updated by the study team: 2017-12-02

Who can join

Age: 18 and older, up to 55. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Only patients requiring a double umbilical cord blood (UCB) transplant are to be considered for this study.
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

You may not qualify if…

Available medically suitable HLA-identical related donor
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)

Where it is running

Masonic Cancer Center, University of Minnesota — Minneapolis, Minnesota, United States

Full record on ClinicalTrials.gov

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