Allogenic CD123-CAR-NK Cells in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia
Study Details
Study Description
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 and maximum tolerated dose of CD123-CAR NK cells given to these patients.
Condition or Disease | Intervention/Treatment | Phase |
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Early Phase 1 |
Detailed Description
This is a dose-escalation 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Experimental: Experimental: CD123-CAR-NK. The relapsed/refractory AML patients will receive allogenic CD123-Targeted CAR-NK cells infusion up to 3 dose levels (1x10^6/kg, 5x10^6/kg, 2x10^7/kg) after FC chemotherapy. |
Biological: CD123-CAR-NK cells
CD123-CAR-NK is an allogenic CD123-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.
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Outcome Measures
Primary Outcome Measures
- Dose limiting toxicities (DLTs) [1 Months]
- Treatment-emergent adverse events [3 months]
- Treatment-related adverse events [3 months]
Secondary Outcome Measures
- Complete response (CR) [3 months]
- Progression free survival (PFS) [12 months]
- Overall Survival (OS) [12 months]
- Proportion of subjects with minimal-residual disease (MRD) negative response [3 months]
- The area under the concentration time-curve (AUC) of CD123-CAR-NK cells [3 Months]
- Peak levels of CD123-CAR-NK cells (maximum concentration or Cmax) [3 Months]
Eligibility Criteria
Criteria
Inclusion criteria:
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Age ≥ 18 years old, no gender or race;
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Expected survival period ≥ 3 months;
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Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
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The diagnosis of AML with bone marrow biopsy, immunohistochemistry or Flow cytometry definitively positive for CD123 and met the following criteria:
- 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;
- Adequate organ function:
- 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%;
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Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.;
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Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
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Central nervous system involved;
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Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide;
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Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids);
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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.
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History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
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Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment;
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Women who are pregnant (urine/blood pregnancy test positive) or lactating;
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Suffering from a serious autoimmune disease or immunodeficiency disease; 9 Suffering from mental illness;
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Known alcohol dependence or drug dependence; 11. According to the investigator's judgment, the patient has other unsuitable grouping conditions.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital | Beijing | Beijing | China | 100071 |
Sponsors and Collaborators
- Affiliated Hospital to Academy of Military Medical Sciences
- Beijing JD Biotech Co. LTD.
Investigators
- Principal Investigator: Liangding Hu, Docotr, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAR-NK123-JD