This phase I/II trial studies the side effects of laboratory-treated (central memory/naive) cluster of differentiation 8+ T cells (autologous Wilms tumor \[WT\]1-T cell receptor \[TCRc\]4 gene-transduced CD8-positive central memory T-cells \[TCM\]/naive T cells \[TN\] lymphocytes) and how well it works in treating patients with acute myeloid leukemia that is newly diagnosed or has come back. Genetically modified therapies, such as autologous WT1-TCRc4 gene-transduced CD8-positive TCM/TN lymphocytes, are taken from a patient's blood, modified in the laboratory so they specifically may kill cancer cells with a protein called WT1, and safely given back to the patient. The "genetically modified" T-cells have genes added in the laboratory to allow them to recognize leukemia cells that express WT1 and kill them.
PRIMARY OBJECTIVES: I. Determine the safety/potential toxicities associated with treating high-risk acute myeloid leukemia (AML) patients with autologous CD8+ T cells (polyclonal Tn and Tcm cells; Epstein-Barr virus-specific T cells \[Tebv cells\]) that have been genetically-modified to express a high affinity WT1-specific TCR (TCRC4). II. Determine the feasibility of reproducibly treating high-risk AML patients with autologous CD8+ T cells (polyclonal TN and TCM cells; Tebv cells) that have been genetically-modified to express a high affinity WT1-specific TCR (TCRC4). III. Determine and compare the in vivo persistence in blood and at the primary tumor site (e.g. bone marrow, chloroma) of transferred autologous CD8+ T cells (polyclonal TN and TCM cells; TEBV cells) that have been genetically-modified to express a high affinity WT1-specific TCR (TCRC4). EXPLORATORY OBJECTIVES: I. Determine whether adoptively transferred autologous TCRC4-transduced CD8+ cells have anti-tumor activity in patients with acute myeloid leukemia. Ia. In patients with measurable minimal residual disease (MRD) at the time of infusion of TCRC4-transduced CD8+ cells, changes in leukemic tumor burden will be measured by morphology, flow cytometry, cytogenetics/fluorescence in situ hybridization (FISH) and/or molecular testing at baseline and after infusion of T cells. Ib. In all patients (those with or without measurable tumor burden prior to T cell transfer, including patients who convert to MRD-negative status during consolidation), the probability of relapse, disease-free survival and overall survival of patients receiving TCRC4-transduced CD8+ cells will be compared with patients in the observation arm. II. Determine and compare the migration to the primary tumor site of subsets of the adoptively transferred autologous TCRC4-transduced CD8+ T cells (polyclonal TN and TCM cells; TEBV cells). III. Determine and compare the in vivo functional capacity of transferred polyclonal autologous TCRC4-transduced CD8+ TCM, TN cells and TEBV CD8+ cells. OUTLINE: Beginning 4 weeks after completion of last course of consolidation chemotherapy, patients receive autologous WT1-TCRc4 gene-transduced CD8+ TCM/TN lymphocytes intravenously (IV) over 1-4 hours on day 0 and again after a minimum of 3 weeks. Beginning 6 hours after the second infusion of T cells, patients also receive aldesleukin subcutaneously (SC) twice daily (BID) for 14 days in the absence of disease progression or unacceptable toxicity. Patients who have clinically benefitted from T cell therapy may receive additional infusions of T cells and aldesleukin at the discretion of the principal investigator (PI) and the attending physician. After completion of study treatment, patients are followed up weekly for 4 weeks, at 2, 3, 6, and 12 months, and then annually for 14 years thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Number of Participants Who Experienced at Least One Serious Adverse Event (SAE)
Evidence and nature of toxicities will be measured according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.This is the number of participants who experienced at least one adverse event (SAE).
Time frame: 12 months after the last infusion
Feasibility of Subsets
Feasibility of generating TCR-transduced TN and TCM subsets for adoptive immunotherapy in a high-risk AML population. This is the proportion of subjects who sign the treatment consent, have a T cell product generated, and ultimately receive the study intervention.
Time frame: Up to 6 weeks
Number of Participants Whose Treatment Resulted in TCRC4-transduced CD8+ Polyclonal TCM and TN Cell Persistence.
Comparison of the relative frequencies and duration of persistence of adoptively transferred TCRC4-transduced CD8+ polyclonal TCM and TN cells, and of TCRC4-transduced TEBV CD8+ cells in blood and at the primary tumor site(s). This is the number of participants whose blood samples displayed TCRC4-transduced CD8+ polyclonal TCM and TN cell Persistence in follow up.
Time frame: 12 months after the last infusion
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