Adult patients with refractory or relapsed CD123+ hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or blastic plasmocytoid dentritic cell neoplasm will be recruited in the trial. CART123 cells will be manufatured from blood of each patient. During the production of CAR123 cells, patients may receive appropriate bridging therapy. After cells are produced, participants will undergo a single course of lymphodepleting chemotherapy and receive a single dose of CAR123 T cells. The trial will establish the recommended dose for further studies, either the Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD). Patients must be eligible for hematopoietic stem cell transplantation in order to participate in the trial.
CD123 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry.
Age between 18 and 70 years.
Patient has a suitable donor for allogeneic hematopoietic stem cell transplantation. Workup and clearance of the donor must be completed before IMP administration.
Patient able to understand and sign informed consent.
Known hypersensitivity to any component of the IMP.
Allogeneic HSCT within 3 months prior to IMP administration.
Severe, uncontrolled active infection.
Life expectancy < 8 weeks.
Single group
Autologous CAR123 T lymphocytes
Biological/VaccineAnti-CD123 Chimeric Antigen Receptor (CAR) T-Cells (CART123)
Safety and tolerability of autologous CART123 cells
Cumulative incidence of IMP-related adverse events (AEs) graded by ASTCT consensus grading criteria for Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) and by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 for other AEs
Rate of hematological recovery
Rate of hematological recovery, defined as absolute neutrophil count (ANC) \> 1x 10\^9/L and platelet count \> 20x10\^9/L without transfusion support. Hematological recovery before and after HSCT will be evaluated separately.
A dose of CART123 cells for further study
Incidence of dose-limiting toxicities (DLTs) and other safety data after IMP administration.
Morphologic Leukemia Free State (MLFS).
Efficacy of IMP administration in patients with refractory or relapsed AML, MDS, BPDCN and ALL evaluated by rate of morphologic leukemia-free state (MLFS).
Complete Remission (CR) rate
Efficacy of IMP administration in patients with refractory or relapsed AML, MDS, BPDCN and ALL evaluated by Complete Remission (CR) rate.
Median Overall Survival and Overall Survival
Efficacy of IMP administration in patients with refractory or relapsed AML, MDS, BPDCN and ALL evaluated by overall survival (OS)
Feasibility and need for allogeneic hematopoietic cell transplantation after IMP administration
Proportion of patients who did not recover blood counts within 28 days of IMP administration, proportion of patients who received allogeneic haematopoietic stem cell transplantation, and who engrafted after transplant.
Determination of persistence and phenotype of CART123 cells in peripheral blood and bone marrow.
Number (absolute and percentage of T lymphocytes) of CART123 cells in peripheral blood and bone marrow.
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