Acute Myeloid Leukemia Recurrent, Acute Myeloid Leukemia Refractory
Conditions
Brief summary
The CD123-Targeted CAR-NK cell therapy is a new treatment that is being investigated for treatment of acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety of CD123-CAR NK cells given to these patients.
Detailed description
This is a study of allogenic CD123-CAR NK cells. The relapsed/refractory AML patients will receive FC (F, Fludarabine, C, Cyclophosphamide) chemotherapy followed by infusion of CD123-CAR-NK cells. No graft-versus-host disease (GVHD) prevention will be conducted before or after infusion. Dose-limiting toxicity, incidence of adverse events, disease response and PK/PD will be detected post-infusion.
Interventions
BIOLOGICALCD123-CAR-NK cells
CD123-CAR-NK is an allogenic CD123-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.
Sponsors
Beijing JD Biotech Co. LTD.
Affiliated Hospital to Academy of Military Medical Sciences
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Evaluate the safety of JD023 injection.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old, no gender or race; 2. Expected survival period ≥ 3 months; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; 4. The diagnosis of AML with bone marrow biopsy, immunohistochemistry or Flow cytometry definitively positive for CD123 and met one of the following criteria: A. Diagnostic criteria for relapsed AML: after complete remission (CR), leukemia cells reappeared in peripheral blood or blast cells in bone marrow ≥ 5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; B. Diagnostic criteria for refractory AML: naive patients who were ineffective after 2 courses of standard regimens; patients relapsed within 12 months who underwent consolidation and intensive therapy after CR; patients relapsed after 12 months but were ineffective after conventional chemotherapy; Patients with two or more relapses; patients with persistent extramedullary leukemia; C. Patients eligible for relapsed or refractory AML remained minimally residual disease positive after salvage therapy 5. Adequate organ function: A. Liver function: ALT≤3×ULN, AST≤3×ULN, total bilirubin≤2×ULN; B. Coagulation function: international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤ 1.5×ULN; C. Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30mL/min; D. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; 6. Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.; 7. Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.
Exclusion criteria
1. Central nervous system involved; 2. Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide; 3. Systemic use of hormones within 2 weeks prior to enrollment (except for patients with inhaled corticosteroids); 4. Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: HBV, HCV, HIV, syphilis infection, or active pulmonary tuberculosis. 5. History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines; 6. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment; 7. Women who are pregnant (urine/blood pregnancy test positive) or lactating; 8. Suffering from a serious autoimmune disease or immunodeficiency disease; 9 Suffering from mental illness; 10\. Known alcohol dependence or drug dependence; 11. According to the investigator's judgment, the patient has other unsuitable grouping conditions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicities (DLTs) | 1 Months |
| Treatment-emergent adverse events | 3 months |
| Treatment-related adverse events | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with minimal-residual disease (MRD) negative response | 3 months |
| Complete response (CR) | 3 months |
| Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax) | 3 Months |
| The area under the concentration time-curve (AUC) of CD123-CAR-NK cells | 3 Months |
| Progression free survival (PFS) | 12 months |
| Overall Survival (OS) | 12 months |
Countries
China
Contacts
Primary ContactLiangding Hu, Doctor
Backup ContactYao Sun, Doctor
Outcome results
None listed