Clinical trial NCT06707259: Clinical Study of Cord Blood-derived IL-10 CD19-CAR NK in the Treatment of Refractory/Relapsed B-cell NHL
Official title: Clinical Study of Cord Blood-derived IL-10 CD19-CAR NK in the Treatment of Refractory/Relapsed B-cell NHL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-cell Non Hodgkin Lymphoma
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2024-11-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To study the safety and effectiveness of cord blood-derived IL-10 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 CD19-CAR NK cells. 6-24 patients are planned to be enrolled in the dose-escalation trial (2×10\^6 cells/kg, 3×10\^6 cells/kg, 4×10\^6 cells/kg). 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.

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.

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLTs)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Complete response rate (CR)
timeFrame: Up to 2 years
measure: Progression free survival (PFS)
timeFrame: Up to 2 years
measure: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Partial response rate (PR)
timeFrame: Up to 2 years
measure: Overall response rate (ORR)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: the Second Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: