B-cell Non Hodgkin Lymphoma
Conditions
Brief summary
To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma
Detailed description
This is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualCAR-NK19/70 cells in patients with B-cell non-Hodgkin lymphoma.9-18 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) . Each dose was given once a week for 3 weeks.The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled to estimate the safety and efficacy of CB CAR-NK019 under the best dose.
Interventions
BIOLOGICALCB dualCAR-NK19/70
Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15
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. Voluntarily participate in the study and sign the informed consent; 2. Age 18-75, male and female; 3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types: (1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based; 4\. There was at least one measurable lesion with the longest diameter ≥1.5 cm; 5\. Predicted survival ≥12 weeks; 6\. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive; 7\. ECOG score 0-2; 8\. Adequate reserve of organ functions: 1. cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal); 2. creatinine clearance (Cockcroft - Gault method) or 60 mL/min. 3. serum total bilirubin and alkaline phosphatase (1.5 x or less UNL. 4. glomerular filtration rate \> 50 mL/min 5. heart ejection fraction (EF) 45% or higher; 6. indoor natural air environment, basic oxygen saturation \> 92% 7. blood routine: neutrophils absolute number \> 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin; 9\. Allowed to have received a previous stem cell transplant 10\. Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks; 11\. Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted; 12\. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial 13\. Two tests have come back negative for COVID-19.
Exclusion criteria
1. Allergic to any of the components of cell products; 2. History of other tumors; 3. Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD; 4. Had received gene therapy in the past 3 months; 5. Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed; 6. Subjects infected with hepatitis B (HBsAg positive, but HBV-DNA\<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons; 7. Subjects with Grade III or IV cardiac insufficiency according to the New York Heart Association Cardiac Function Grading criteria; 8. Patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (CTCAE 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia); 9. Subjects with a history of epilepsy or other central nervous system diseases; 10. Skull enhanced CT or MRI showing evidence of central nervous system lymphoma; 11. Lactating women who refuse to stop breastfeeding; 12. Any other circumstances 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, tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Up to 2 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Duration of response (DOR) | Up to 2 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Overall survival (OS) | Up to 2 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Partial response rate (PR) | Up to 2 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Progression free survival (PFS) | Up to 2 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Complete response rate (CR) | Up to 2 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
Countries
China
Contacts
Primary ContactWenbin Qian, PhD
Backup ContactHui Liu, PhD
Outcome results
None listed