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.
Gender is not limited, age 18-75 years old (including the threshold value);
The expression of CD123 in tumor cells was detected by flow cytometry.
Patients with relapsed/refractory AML or BPDCN diagnosed with CD123 positive: 1) AML: a. Recurrent: After complete response (CR), the recurrence of leukemia cells in peripheral blood or bone marrow original cells ≥5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or the occurrence of extramedullary leukemia cell infiltration; b. Refractory: refers to those who have failed to receive 2 courses of treatment with standard protocols; Patients recurrence within 12 months after CR with consolidation and intensive treatment; Recurrence after 12 months but failed to respond to conventional chemotherapy; 2 or more relapses; Extramedullary leukemia persists;
Cardiac function: echocardiography indicated cardiac ejection fraction ≥50%, and no obvious abnormality was found in electrocardiogram;
Prior to screening, the following anti-tumor therapies were received: chemotherapy, targeted therapy, or other investigational drug treatment within 14 days or at least 5 half-lives (whichever is shorter), except in cases where disease progression has been confirmed after treatment;
had a cerebrovascular accident or seizure within 6 months before signing the ICF;
There is an active or uncontrolled infection that requires systemic treatment within 1 week prior to screening;
New York Heart Association (NYHA) Stage III or IV congestive heart failure;
Parallel
CD123 targeted CAR-NK cells
Biological/VaccineAdministration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
To evaluate the safety of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Safety and Tolerability]
The incidence of adverse events after CD123 CAR-NK cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)
To evaluate the efficacy of CAR-NK cell preparations in the treatment of Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
Objective response rate at 4W±7D and 3M±7D after CAR-NK infusion (Objective response rate includes CR, CRi)
AUCS of CD123 CAR-NK cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
CMAX of CD123 CAR-NK cells [Cell dynamics]
CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood
TMAX of CD123 CAR-NK cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Pharmacodynamics of CD123 CAR-NK cells[Cell dynamics]
The degree of clearance of malignant cells in peripheral blood was detected by blood smear at each time point，and the concentration level of serum cytoplasmic factors such as CRP and IL-6 were detected by ELISA at each time point
Duration of Response (DOR) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause
Progress-free survival(PFS) of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
PFS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause or the first assessment of progression
Overall survival(OS)of CD123 CAR-NK treatment in patients with Relapsed/Refractory Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm[Effectiveness]
OS will be assessed from the first CD123 CAR-NK cell infusion to death from any cause
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Chongqing Precision Biotech Co., Ltd
Lead sponsor
Shanxi Bethune Hospital
Collaborator
