Phase I Study of Adoptive Immunotherapy With CD8+ and CD4+ Memory T Cells Transduced to Express an HA-1-Specific T Cell Receptor (TCR) for Children and Adults With Recurrent Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation (HCT)
Summary
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.
Detailed description
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.
Arms & interventions
- BiologicalCD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR
Given IV
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBiospecimen Collection
Undergo blood sample collection
Outcome measures
Primary
Feasibility 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
Secondary
Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood
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
Time frame: Up to 1 year
Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow
Time frame: Up to 1 year
Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow
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
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
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
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
Time frame: Up to 1 year
Proportion of subjects who develop new or recurrent symptoms or signs of graft-versus-host disease
Time frame: Up to 1 year
Eligibility criteria
Study locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
References
- Krakow EF, Brault M, Summers C, Cunningham TM, Biernacki MA, Black RG, Woodward KB, Vartanian N, Kanaan SB, Yeh AC, Dossa RG, Bar M, Cassaday RD, Dahlberg A, Till BG, Denker AE, Yeung CCS, Gooley TA, Maloney DG, Riddell SR, Greenberg PD, Chapuis AG, Newell EW, Furlan SN, Bleakley M. HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Blood. 2024 Sep 5;144(10):1069-1082. doi: 10.1182/blood.2024024105.(PubMed)