Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

The goal of this clinical trial is to study the efficacy of the tagraxofusp + venetoclax combination in treatment-naive blastic plasmacytoid dendritic cell neoplasm adult patients. The main question is to verify the response in patients after 3 cycles of tagraxofusp+venetolax and to demonstrate if the combination of tagraxofusp + venetoclax increases the rate of complete remission, assessed after 3 months of treatment. Patients will receive a ramp-up phase of venetoclax during 3 days and at least 3 cycles of venetoclax. After, the investigators will evaluate the response, and depending on the response observed, patients may receive additional cycles of treatment for a maximum of 24 cycles, or receive an allograft or discontinue the treatment in the case of therapeutic failure.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a very rare hematologic malignancy. Despite recent advances, at present there is no consensus on the optimal treatment of BPDCN. The optimal therapy of disease remains to be determined, and due to the rarity of cases, there is a need for international collaboration to collect data on BPDCN clinical presentations, diagnostics, treatment regimens and outcomes. Therefore, the objectives of this study are: (1) to build a large database of patients with BPDCN, (2) to investigate the characteristics and outcome of the disease with different treatment regimens, (3) to evaluate prognostic factors, and (4) to generate data-based prospective treatment recommendations.

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.

This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study, aiming to evaluate the safety and efficacy of targeting CD123 CAR-NK cell preparations in Relapsed/refractory acute myeloid leukemia (AML) or blastocytic plasmacytoid dendritic cell neoplasm (BPDCN). The pharmacokinetic characteristics of CAR-NK cell preparations for the treatment of patients with Relapsed/refractory acute myeloid leukemia or blastocytic plasmacytoid dendritic cell neoplasm were obtained and the recommended dose.