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

Overview

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.

Interventions

• Biological anti-CD19 IL10/IL15 CAR-NK
  Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19-IL10/IL-15 CAR

Primary outcome measures

• Incidence of dose limiting toxicity (DLTs) [Time frame: Up to 28 days]

Secondary outcome measures (6)

• Complete response rate (CR) [Time frame: Up to 2 years]
• Progression free survival (PFS) [Time frame: Up to 2 years]
• Duration of response (DOR) [Time frame: Up to 2 years]
• Overall survival (OS) [Time frame: Up to 2 years]
• Partial response rate (PR) [Time frame: Up to 2 years]
• Overall response rate (ORR) [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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;
• 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;
• 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;

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the Second Affiliated Hospital, College of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT06707259 · 2024（1369）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗