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

NCT ID: NCT06707259

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2027-12-01

Brief Summary

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

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.

Conditions

B-cell Non Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CB IL-10/IL-15-CD19-CAR NK

All subjects were intravenously administrated with IL-10/IL-15 CD19-CAR NK

Group Type: EXPERIMENTAL

anti-CD19 IL10/IL15 CAR-NK

Intervention Type: BIOLOGICAL

Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19-IL10/IL-15 CAR

Interventions

anti-CD19 IL10/IL15 CAR-NK

Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19-IL10/IL-15 CAR

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

the Second Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenbin Qian, Professor

Role: CONTACT

qianwb@zju.edu.cn

+8613605801032

Hui Liu, Doctor

Role: CONTACT

sylen@zju.edu.cn

13819198629

Facility Contacts

Wenbin Qian, Professor

Role: primary

qianwb@zju.edu.cn

13605801032

Hui Liu, Doctor

Role: backup

sylen@zju.edu.cn

13819198629

Other Identifiers

2024（1369）

Identifier Type: -

Identifier Source: org_study_id