CAR-NK Targeted CD19 for r/r B-cell Malignancies

Study Overview
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Brief Summary
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This is a single-centre, single-arm and open-label study to investigate the safety and efficacy of JD010 in adult patients with relapsed or refractory B cell hematologic malignancies. JD010 injection is a CD19-targeted chimeric antigen receptor modified natural killer cells (CAR-NK) derived from a healthy donor

Official Title
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Early Clinical Study of Allogenic CAR-NK Targeted CD19 (JD010) in the Treatment of Adult Relapsed or Refractory B-cell Malignancies

Conditions
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Adult Relapsed/Refractory B-cell Hematologic Malignancies

Intervention / Treatment
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* Biological: CD19-CAR-NK


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 18 years old, no gender or race; Expected survival period ≥ 3 months; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2; Confirmed relapsed/refractory B-cell malignancies and tumor cells expressing CD19; 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%; Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.; Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Central nervous system involved; Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide; Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids); 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. History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines; Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment; Women who are pregnant (urine/blood pregnancy test positive) or lactating; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19 CAR-NK(JD010)<br>CD19-CAR-NK is an allogenic CD19-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy. | Biological: CD19-CAR-NK<br>* The relapsed/refractory B-cell hematologic malignancies patients will receive FC (F, Fludarabine, C, Cyclophosphamide) chemotherapy followed by 3 infusions of JD010 cells up to 2 dose levels (5x10^6/kg, 2x10^7/kg) after FC chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLTs) |  | 1 Months | 
| Treatment-related adverse events |  | 3 months | 
| Objective Response Rate (ORR) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) |  | 12 months | 
| Overall Survival (OS) |  | 12 months | 
| Proportion of subjects with minimal-residual disease (MRD) negative response |  | 12 months |