Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence II
Hematology Disease Topics & Pathways:
AML, Biological, Adult, Diseases, CML, CMML, Therapies, MDS, Pediatric, MPN, Technology and Procedures, cell expansion, Young Adult, Study Population, Myeloid Malignancies, Clinically relevant, transplantation, stem cells
Study Design and Methods: The single-center phase I trial (NCT03326921) evaluates the feasibility and safety of infusion of HA-1 TCR T-cell immunotherapy. Primary end points are 1) Feasibility of manufacturing and administering HA-1 TCR CD8+ and CD4+ memory T cells and 2) Dose-limiting toxicity of HA-1 TCR T cells. Major inclusion criteria are: HLA-A*02:01-positive, HA-1-positive patients who underwent HCT for acute leukemia, myelodysplastic syndrome, BPDCN, CML, CMML or JMML from a HLA-A*-02:01+/HA-1-negative donor or HLA-A*02:01-negative haploidentical or mismatched donor (excluding umbilical cord). HA-1 genotype screening is performed on patient and donor blood, hair follicle or cheek swab samples shipped to Fred Hutchinson Cancer Research Center. To be eligible for treatment, patients must develop measurable residual disease or overt relapse after HCT but may receive other standard or investigational therapies prior to treatment with HA-1 TCR T-cell immunotherapy if clinically indicated. Some systemic immunosuppression may be continued, but prior grade IV acute GVHD and prior severe chronic GVHD are key exclusions. Two groups, <16 and ≥16 years, will be treated at dose levels ranging from 3 x 106 to 30 x 106 cells/kg, in cohorts of 3-6 subjects, up to approximately 24 subjects in total. Fludarabine lymphodepletion will be used in most subjects, followed by a single T-cell infusion, with an option for a subsequent infusion(s) if the subject demonstrates an initial response without severe toxicity. Bone marrow aspirations are performed prior to T-cell infusion and at several time points following infusion.
Recruitment and Patient Characteristics: To date, 3 subjects have been treated on the phase I clinical trial and received a total of 5 infusions (Table 1). HA-1 TCR T cell persistence in blood and bone marrow has been documented from >3 months to >13 months. Clear in vivo anti-leukemic activity was observed at the first dose level, including in a subject with aggressive, highly refractory T-ALL and early post-HCT relapse.
Outlook: Minor H antigen-specific T-cell immunotherapy may offer effective management of post-HCT relapse while avoiding GvHD and other off-target effects. Due to population genetics of HA-1 and HLA-A*02:01, HA-1 TCR T-cell immunotherapy is applicable to 10-15% of HCT recipients with various hematological malignancies. The ongoing phase I trial is actively recruiting patients. Development of T-cell immunotherapy targeting other minor H antigen/HLA combinations is also underway to increase the broad applicability of minor H antigen-targeted T-cell immunotherapy.
Disclosures: Krakow: HighPass Bio: Research Funding. Cunningham: HighPass Bio: Research Funding. Vartanian: HighPass Bio: Research Funding. Bleakley: HighPass Bio: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.
See more of: Oral and Poster Abstracts