Using cord blood-derived CAR NK cells to treat refractory B-cell lymphoma

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

This study is testing a new treatment using special immune cells from cord blood to see if it can help people with hard-to-treat B-cell lymphoma feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06707259 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of cord blood-derived IL-10 CD19-CAR NK cells in patients with refractory or relapsed B-cell non-Hodgkin lymphoma. It is an open-label, single-arm, dose-escalation study that plans to enroll 6-24 patients, administering escalating doses of the CAR NK cells. The primary endpoints include determining the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), while secondary endpoints focus on overall response rates, survival, and progression-free survival. Patients will receive infusions on specific days following enrollment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with refractory or relapsed B-cell non-Hodgkin lymphoma who have failed previous treatments.

Not a fit: Patients with early-stage B-cell lymphoma or those who have not undergone prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell non-Hodgkin lymphoma.

How similar studies have performed: While the use of CAR NK cells is a novel approach, similar studies have shown promise in treating other hematological malignancies.

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.

Where this trial is running

Hangzhou, Zhejiang

• the Second Affiliated Hospital, College of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Wenbin Qian, Professor

Conditions B-cell Non Hodgkin Lymphoma