B-cell Non Hodgkin Lymphoma
Conditions
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.
Interventions
BIOLOGICALanti-CD19 IL10/IL15 CAR-NK
Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19-IL10/IL-15 CAR
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicity (DLTs) | Up to 28 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial response rate (PR) | Up to 2 years | — |
| Overall response rate (ORR) | Up to 2 years | — |
| Overall survival (OS) | Up to 2 years | — |
| Progression free survival (PFS) | Up to 2 years | — |
| Duration of response (DOR) | Up to 2 years | — |
| Complete response rate (CR) | Up to 2 years | To determine the anti-tumor effectivity of CB IL-10-CD19-CAR NK |
Countries
China
Contacts
Primary ContactWenbin Qian, Professor
Backup ContactHui Liu, Doctor
Outcome results
None listed