allogeneic cd19 car-t cells for the treatment of relapsed/refractory b-cell acute lymphoblastic leukemia

Conditions: Relapse Leukemia; Refractory Leukemia

Summary: cd19 car-t has been widely developed in patients with r/r all and has also been generally recognized by the industry. in 2017, the u.s. fda approved novartis's cd 19 car-t product kymriah for the treatment of r/r all. however, these car-t cells are constructed from patients' autologous t cells, and the production and preparation time is long; on the other hand, most patients have received multiple chemotherapy before car-t treatment, and the quantity and quality of t cells often cannot meet the needs of clinical treatment. it is also an important factor leading to the failure of car-t cell therapy, which limits the large-scale clinical application of car-t. t cells derived from healthy donors are not only sufficient in quantity and quality guaranteed, but also available at any time. in december 2020, lancet reported a clinical study of 19 patients receiving allogeneic car-t cell all. 14 patients were evaluated as cr/cri (67%) 28 days after treatment, and the median sustained remission time was 4.1 moon. allogeneic car-t cells are safe and effective for the treatment of all, and their clinical application range is expected to improve the remission rate and survival rate of patients with r/r all.

chimeric antigen receptor (car) t cells enable t cells to recognize and kill tumor cells that express specific antigens through genetic engineering. cd19 is expressed on the membrane surface of pre-b cells and mature b cells, but not on the surface of t cells and normal granulocytes. it is an ideal therapeutic target for b cell-derived tumors. a large number of previous studies have confirmed that cd19 car-t cells are a safe and effective method for the treatment of all. in 2018, new england journal published the long-term follow-up data of cd19 car-t for relapse/refractory (r/r) all, 53 patients with r/r all who received a single infusion of cd19 car-t the response efficiency (cr+pr) reached 98%, of which about 83% of cr patients, with a median survival time of 12.9 months; greatly improved the remission rate and survival rate of r/r all patients. nowadays,cd19 car-t has been widely developed in patients with r/r all and has also been generally recognized by the industry. in 2017, the u.s. fda approved novartis's cd car-t product kymriah for the treatment of r/r all. however, these car-t cells are constructed from patients' autologous t cells, and the production and preparation time is long; on the other hand, most patients have received multiple chemotherapy before car-t treatment, and the quantity and quality of t cells often cannot meet the needs of clinical treatment. it is also an important factor leading to the failure of car-t cell therapy, which limits the large-scale clinical application of car-t. t cells derived from healthy donors are not only sufficient in quantity and quality guaranteed, but also available at any time. in december 2020, lancet reported a clinical study of 19 patients receiving allogeneic car-t cell all. 14 patients were evaluated as cr/cri (67%) 28 days after treatment, and the median sustained remission time was 4.1 moon. allogeneic car-t cells are safe and effective for the treatment of all, and their clinical application range is expected to improve the remission rate and survival rate of patients with r/r all.

Eligibility criteria:
inclusion criteria: 1. 14-70 years old (including 14, 70 years old), no gender limit; 2. according to the 2020 world health organization (who) diagnostic criteria, it is diagnosed as relapsed/refractory b-cell acute lymphoblastic leukemia (r/r b-all); 3. the ecog behavior status score is 0-2 points; 4. expected survival time ≥ 3 months; 5. flow cytometry confirms that the original cells express cd19; 6. those who have failed autologous car-t cell preparation or autologous car-t cell therapy under the existing technical conditions; 7. no serious heart, lung, liver, or kidney disease; 8. ability to understand and willing to sign the informed consent form for this trial. exclusion criteria: 1. primitive cells do not express cd19; 2. active infection; 3. abnormal liver function (total bilirubin\>1.5×uln, alt\>2.5×uln), abnormal renal function (serum creatinine\>1.5×uln); 4. people with unstable angina or new york heart association class 3/4 congestive heart failure, multiple organ dysfunction; 5. hiv/aids patients; 6. those who need long-term anticoagulation (warfarin or heparin), antiplatelet (aspirin, dose\>300mg/d; clopidogrel, dose\>75mg/d) treatment; 7. those who received radiotherapy within 4 weeks before the start of the study; 8. known or suspected drug abuse or alcohol dependence; 9. people with mental illness or other conditions cannot obtain informed consent, and cannot cooperate with the requirements of completing the experimental treatment and inspection procedures; 10. participated in other clinical trials within 30 days; 11. pregnant or lactating women, male subjects (or their partners) or female subjects have a pregnancy plan during the study period to 6 months after the end of the test, and are unwilling to use a medically approved effective contraceptive measure during the test period (such as intrauterine contraceptive devices or condoms); 12. those who are judged by the investigator to be unsuitable to participate in this trial.