Clinical Study of Cord Blood-derived IL-10/IL-15 CD19-CAR NK in the Treatment of Refractory/Relapsed B-cell NHL

To study the safety and effectiveness of cord blood-derived IL-10/IL-15 CD19-CAR NK in patients with B-cell non-Hodgkin's lymphoma

Study Overview

• Status: Recruiting
• Conditions: B-cell Non Hodgkin Lymphoma
• Intervention / Treatment: Biological: anti-CD19 IL10/IL15 CAR-NK

Detailed Description

This is an open, single-arm, single-dose, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CB IL-10/IL-15 CD19-CAR NK cells. 6-24 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg,4×10^6 cells/kg, 8×10^6 cells/kg). Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled in the dose-expansion trial. The primary endpoints are DLT and MTD; the second is the overall response rates (CR and PR), survival, and progression-free survival. Patients will be infused on day 0, day 3, and day 6， respectively.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenbin Qian， Professor; Phone Number: +8613605801032; Email: qianwb@zju.edu.cn
• Study Contact Backup: Name: Hui Liu, Doctor; Phone Number: 13819198629; Email: sylen@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • The Second Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Hui Liu, Doctor; Phone Number: 13819198629; Email: sylen@zju.edu.cn
      • Contact: Wenbin Qian, Professor; Phone Number: 13605801032; Email: qianwb@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Volunteer to participate in this study and sign an informed consent form;
2. Age 18-75 years old, no gender limit;
3. Histologically diagnosed as diffuse large B-cell lymphoma (DLBCL), transforming follicular lymphoma (TFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL) and other inert B-cells NHL conversion type:(1) Refractory or relapsed DLBCL refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ； (2) Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors; (3) Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment; (4) Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines;
4. At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;
5. The expected survival period is ≥12 weeks;
6. The puncture section of the tumor tissue was positive for CD19 expression; 7, ECOG score 0-2 points;
7. Sufficient organ function reserve: (1) Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); (2) Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min; (3) Serum total bilirubin and alkaline phosphatase ≤1.5× UNL; （4）Glomerular filtration rate>50Ml/min Cardiac ejection fraction (EF) ≥50%; (5) Under natural indoor air environment, basic oxygen saturation>92% .
8. Allow a previous stem cell transplantation.
9. The approved anti-B-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication;
10. Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;
11. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial.
12. Two tests for the new coronavirus were negative.

Exclusion Criteria:

1. Those who have a history of allergies to any of the ingredients in cell products;
2. History of other tumors;
3. Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment;
4. Have received gene therapy in the past 3 months;
5. Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed;
6. Hepatitis B (HBsAg positive, but HBV-DNA <103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including but not limited to people living with HIV;
7. According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV impaired subjects;
8. Those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the CTCAE 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss);
9. Subjects with a history of epilepsy or other central nervous system diseases; 10. Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma;

11. Have any other drugs that target CD19; 12. Women who are breastfeeding and unwilling to stop breastfeeding; 13. Any other situation that the investigator believes may increase the subject's risk or interfere with the test results.

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: CB IL-10/IL-15-CD19-CAR NK; All subjects were intravenously administrated with IL-10/IL-15 CD19-CAR NK	Biological: anti-CD19 IL10/IL15 CAR-NK; Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19-IL10/IL-15 CAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLTs)	To evaluate the safety, and tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 IL10/IL15-CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		Up to 2 years
Overall response rate (ORR)		Up to 2 years
Duration of response (DOR)		Up to 2 years
Complete response rate (CR)	To determine the anti-tumor effectivity of CB IL-10-CD19-CAR NK	Up to 2 years
Progression free survival (PFS)		Up to 2 years
Partial response rate (PR)		Up to 2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 24, 2024
• First Submitted That Met QC Criteria: November 24, 2024
• First Posted (Actual): November 27, 2024

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell
• Other Study ID Numbers: 2024（1369）

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
• product manufactured in and exported from the U.S.: No