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

NCT06707259 | Recruiting Phase 1 DMC

• 1 other identifier: 2024（1369）
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

B-cell Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Complete response rate (CR)

  Up to 2 years

• Progression free survival (PFS)

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Partial response rate (PR)

  Up to 2 years

Study Arms (1)

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

EXPERIMENTAL

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

Biological: anti-CD19 IL10/IL15 CAR-NK

Interventions

anti-CD19 IL10/IL15 CAR-NK BIOLOGICAL

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

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer to participate in this study and sign an informed consent form;
• Age 18-75 years old, no gender limit;
• 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;
• At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;
• The expected survival period is ≥12 weeks;
• The puncture section of the tumor tissue was positive for CD19 expression; 7, ECOG score 0-2 points;
• 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% .
• Allow a previous stem cell transplantation.
• 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;
• Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;
• Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial.
• Two tests for the new coronavirus were negative.

You may not qualify if:

• Those who have a history of allergies to any of the ingredients in cell products;
• History of other tumors;
• Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment;
• Have received gene therapy in the past 3 months;
• Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed;
• According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV impaired subjects;
• 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);
• 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;
• \. 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.

Sponsors & Collaborators

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

Study Sites (1)

the Second Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Wenbin Qian, Professor

CONTACT

+8613605801032; qianwb@zju.edu.cn

Hui Liu, Doctor

CONTACT

13819198629; sylen@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2024
• First Posted: November 27, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 20, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)