This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute leukemia that persists, has come back (recurrent) or does not respond to treatment (refractory) following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.
OUTLINE: This is a dose-escalation study of CD4+ and CD8+ HA-1 TCR T cells. Patients receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide or debulking regimens as specified in the protocol) ending 2-14 days prior to HA-1 TCR T cell administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells intravenously (IV). After completion of study treatment, patients are followed up closely for 12 weeks and then every 6 months for years 1-5, and every year for years 6-15. Initial study activity was funded in part by HighPass Bio, Inc. Current study activity is funded in part by PromiCell Therapeutics, Inc.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Given IV
Undergo bone marrow aspiration
Undergo blood sample collection
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGFeasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells
Proportion of subjects for whom a HA-1 TCR T cell product can be produced.
Time frame: At time of T cell infusion (at day 0)
Feasibility of administering minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells
Proportion of subjects for whom a HA-1 TCR T cell product can be administered.
Time frame: At time of T cell infusion (at day 0)
Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells
Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Time frame: Up to 12 weeks after T-cell infusion
Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood
Evaluated by tetramer and/or molecular tracking e.g. quantitative polymerase chain reaction (qPCR).
Time frame: Up to 1 year
Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD8+ T cells in peripheral blood
Evaluated by tetramer and/or molecular tracking e.g. qPCR.
Time frame: Up to 1 year
Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow
Evaluated by tetramer and/or molecular tracking e.g. qPCR.
Time frame: Up to 1 year
Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow
Evaluated by tetramer and/or molecular tracking e.g. qPCR.
Time frame: Up to 1 year
Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells before adoptive T cell transfer
Assessed by in vitro chromium release assay or equivalent cytotoxicity assay.
Time frame: At the time of T cell infusion (at day 0)
Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells after adoptive T cell transfer
By in vitro chromium release assay or flow cytometric degranulation assay (CD107a) using samples of peripheral blood and/or bone marrow collected from subjects after adoptive T cell transfer.
Time frame: Up to 1 year
Reduction of leukemia in the bone marrow in subjects who have measurable leukemia in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion
Quantified by flow cytometry to determine percentage of leukemic cells in the marrow.
Time frame: Up to 1 year
Reduction of recipient normal hematopoietic cells in the bone marrow in subjects who have measurable recipient normal hematopoietic cells in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion
Quantified by variable number tandem repeat (VNTR) to determine percentage of normal recipient and donor cells in the marrow.
Time frame: Up to 1 year
Proportion of subjects who develop new or recurrent symptoms or signs of graft-versus-host disease
Assessed using clinical evaluation and standard clinical graft versus host disease (GVHD) grading criteria
Time frame: Up to 1 year
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