safety and efficacy evaluation of cd19-ucart

Conditions: Acute Lymphoblastic Leukemia (ALL); Non Hodgkin Lymphoma (NHL)

Summary: the purpose of this study is to evaluate the safety and efficacy of ascending doses of cd19-ucart in patients with relapsed or refractory b-cell hematological malignancies.

cd19-ucart is a kind of "off-the-shelf" product originated from health donor's pbmc.this is a open-label, dose estilation study to evaluate the safety and anti-tumor efficacy of cd19-ucart in the treatment of relapsed or refractory b-cell hematological malignancies.

Eligibility criteria:
inclusion criteria: 1. voluntarily participating in this clinical study and signing the informed consent form; the estimated survival period is at least one month; 2. no other serious cardiopulmonary diseases, and normal liver and kidney functions (except for subjects with tumor lesions in their liver and kidneys); 3. failure of t cell isolation during autologous cart preparation or failure of cart amplification or failure to complete apheresis or disease progression resulting in patients not benefiting from autologous car-t cell therapy; or: t cell percentage in pbmc of peripheral blood ≤ 10%; or the disease is not effectively controlled within one month after autologous car-t transfusion, and the patient cannot receive car-t transfusion again; 4. flow cytometry within two months demonstrated positive expression of cd19 in the tumor (positive rate 50%-90%; or biopsy ≥ 50% within 6 months; or obtaining a biopsy again); 5. hematological indicators: 1) wbc count ≥ 1.5× 10\^9/l; absolute value of neutrophils ≥ 0.8× 10\^9/l; lymphocyte count ≥0.1×10\^9/l;2) hemoglobin ≥ 60g/l;3) platelet count ≥20×10\^9/l; 6. biochemical indicators (except for subjects with tumor foci in liver and kidney): total bilirubin (tbil)≤1.5 times the upper limits of normal (uln); ast and alt≤1.5 \*uln; scr and bun)≤1.5\*uln; biochemical indicators in subjects with liver and kidney invasion should meet: total bilirubin (tbil)≤5 \*uln;ast and alt≤5\*uln; scr and bun ≤ 5\*uln; 7. cardiac function: good hemodynamic stability, and the left ventricular ejection fraction (lvef) ≥ 55%; 8. serum viral ebv-dna, cmv-dna, hiv antibody and syphilis antibody, hbv, hcv virus quantification were all negative; 9. ecog activity status score: 0-2 points; 10. female subjects must have access to effective contraceptive measures (e.g., oral prescription contraceptives, injectable contraceptives, intrauterine devices, double blocking, contraceptive patches, male partner sterilizations) throughout the study period; serum or urine pregnancy test results must be negative at screening and throughout the study; 11. willing to comply with the rules established in this protocol; 12. patients with relapsed/refractory cd19-positive acute b-cell leukemia (b-all, with the age of 1-60 years) or relapsed/refractory b-cell non-hodgkin's lymphoma (b-nhl, with the age of 5-65 years). exclusion criteria: 1. pregnant or lactating women; 2. the following drugs or treatments should be excluded:high-dose glucocorticoids were used within 72h prior to ucar-t infusion, except for physiological alternative therapies;allogeneic cell therapies such as donor lymphocyte transfusion within 6 weeks prior to ucar-t transfusion;gvhd treatment; 3. single extramedullary relapse b-all; 4. suffering from severe mental disorder; 5. active autoimmune diseases requiring immunotherapy; 6. history of other malignant tumors; 7. patients with severe cardiovascular disease; 8. organ function is in the following abnormalities; 9. total bilirubin \> 1.5 times the upper limit of normal unless the patient is gilbert's syndrome; 10. partial thromboplastin time or activated partial thromboplastin time or international normalized ratio \>1.5\*uln；in the absence of anticoagulant therapy; 11. there is an active infectious disease or any major infectious event requiring high-level antibiotics; 12. any condition that, in the opinion of the investigator, may increase the subject's risk or interfere with the test results.