Overview
To study the safety and effectiveness of cord blood-derived CAR-NK cells targeting CD19 in patients with B-cell non-Hodgkin's lymphoma
Description
This is an open, single-arm, single-dose, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CB CAR-NK019 cells. 9-18 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg ,3×10^6 cells/kg, 4×10^6 cells/kg) . 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.
Eligibility
Inclusion 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:
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; 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; ECOG score 0-2 points;
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% 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; Enhanced CT or MRI of the head showed evidence of central nervous system
lymphoma; Have received any other drugs that target CD19; Women who are breastfeeding and
unwilling to stop breastfeeding; Any other situation that the investigator believes may
increase the risk of the subject or interfere with the results of the test.