Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

Zhejiang University

Status and phase

Enrolling

Phase 1

Conditions

B-cell Non Hodgkin Lymphoma

Treatments

Biological: CB dualCAR-NK19/70

Study type

Interventional

Funder types

Other

Identifiers

NCT05667155

2022-088

Details and patient eligibility

About

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

Full 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.

Enrollment

48 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Voluntarily participate in the study and sign the informed consent;
Age 18-75, male and female;
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;

There was at least one measurable lesion with the longest diameter ≥1.5 cm;
Predicted survival ≥12 weeks;
The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive;
ECOG score 0-2;
Adequate reserve of organ functions:
cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal);
creatinine clearance (Cockcroft - Gault method) or 60 mL/min.
serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.
glomerular filtration rate > 50 mL/min
heart ejection fraction (EF) 45% or higher;
indoor natural air environment, basic oxygen saturation > 92%
blood routine: neutrophils absolute number > 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin;
Allowed to have received a previous stem cell transplant
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;
Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted;
Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial
Two tests have come back negative for COVID-19.

Exclusion criteria

Allergic to any of the components of cell products;
History of other tumors;
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;
Had received gene therapy in the past 3 months;
Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;
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;
Subjects with Grade III or IV cardiac insufficiency according to the New York Heart Association Cardiac Function Grading criteria;
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);
Subjects with a history of epilepsy or other central nervous system diseases;
Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;
Lactating women who refuse to stop breastfeeding;
Any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.