Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory
Conditions
Keywords
Acute Myeloid Leukemia, CAR-NK
Brief summary
This is a single-centre, single-arm, open-label, first-in-human (FIH) study to evaluate the safety, tolerability and preliminary efficacy of universal Off-the-shelf CAR-NK cells targeted CD123 (JD123 injection) in the treatment of refractory or relapsed CD123-positive acute myeloid leukemia (AML).
Detailed description
This is a dose-escalation study of CD123-targeted chimeric antigen receptor modified natural killer cells (CAR-NK) derived from a healthy donor. The relapsed/refractory AML patients will receive FC (F, Fludarabine, C, Cyclophosphamide) chemotherapy followed by infusion of JD123 injections. 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
DRUGJD123 injection
JD123 injection is an universal Off-the-shelf CD123-targeted chimeric antigen receptor modified natural killer cells (CAR-NK) therapy derived from a healthy donor.
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
3+3 Phase I
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 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; Patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) C. Minimal Residual Disease (MRD) positive only or relapse: Patient is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment. 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. Active Central nervous system leukemia; 2. Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide; 3. Systemic use of hormones within 4 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 | Description |
|---|---|---|
| 1-month DLTs | 1-month | Dose limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-month Peak | 3-month | Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax) |
| 3-month CR/CRi | 3-month | Complete response (CR) or Complete remission with incomplete recovery(CRi) |
| 3-month AUC | 3-month | The area under the concentration time-curve (AUC) of CD123-CAR-NK cells |
| 1-year OS | 1-year | Overall Survival (OS) |
| 1-year MRD(-) | 1-year | Proportion of subjects with minimal-residual disease (MRD) negative response |
| 1-year PFS | 1-year | Progression free survival(PFS) |
Countries
China
Outcome results
None listed