B-cell Non Hodgkin Lymphoma
Conditions
Brief summary
To study the safety and effectiveness of HLA haploidentical CAR-NK cells targeting CD19 in patients with B-cell non-Hodgkin's lymphoma
Interventions
BIOLOGICALanti-CD19 CAR-NK
lentiviral vector-transducted HLA haploidentical NK cells to express anti-CD19 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: * 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 ； * Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors; * Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment; * 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; 8. Sufficient organ function reserve: * Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); * Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min; * Serum total bilirubin and alkaline phosphatase ≤1.5× UNL; * Glomerular filtration rate\>50Ml/min * Cardiac ejection fraction (EF) ≥50%; * Under natural indoor air environment, basic oxygen saturation\>92% 9. Allow a previous stem cell transplantation 10. 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; 11. Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation; 12. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial 13. 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 received 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 risk of the subject or interfere with the results of the test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicity (DLTs) | Up to 28 days | To evaluate the safety, tolerability, and determine the recommended dosage of Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma |
| The overall response rate(ORR) | Up to 2 years | To determine the anti-tumor effectivity of CAR-NK019 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 2 years | To determine the anti-tumor effectivity of CAR-NK019 |
| progression free survival (PFS) | Up to 2 years | To determine the anti-tumor effectivity of CAR-NK019 |
| Pharmacokinetics of CAR positive cells | Up to 2 years | The copy number of CAR DNA was measured at the preset follow-up time point. |
| Pharmacokinetics of CAR-NK cells | Up to 2 years | The duration of CAR-positive NK cells in circulation was measured by FACs |
Countries
China
Contacts
Primary ContactWenbin Qian
Outcome results
None listed