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

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

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

Study Overview

• Status: Recruiting
• Conditions: Adult Relapsed/Refractory B-cell Hematologic Malignancies
• Intervention / Treatment: Biological: CD19-CAR-NK

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Liangding Hu, Dr; Phone Number: +86 01066947171; Email: huliangding@sohu.com
• Study Contact Backup: Name: Yao Sun, Dr; Phone Number: +86 01066947172; Email: suny320@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital
      • Contact: Liangding Hu, Ph.D; Phone Number: +86-010-6694-7171; Email: huliangding@sohu.com
      • Contact: Yao Sun, Ph.D; Phone Number: +86-010-6694-7172; Email: suny320@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. Confirmed relapsed/refractory B-cell malignancies and tumor cells expressing CD19;

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD19 CAR-NK(JD010); CD19-CAR-NK is an allogenic CD19-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.	Biological: CD19-CAR-NK; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Affiliated Hospital to Academy of Military Medical Sciences
• Collaborators: Beijing JD Biotech Co. LTD.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): May 30, 2024
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: December 1, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Estimate): December 9, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: CAR-NK-JD010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No