anti-cd19 car in piggybac transposon-engineered t cells for relapsed/refractory b-cell lymphoma or b-cell acute lymphoblastic leukemia

Conditions: B Cell Lymphoma; B-cell Acute Lymphoblastic Leukemia

Summary: our previous study demonstrated that anti-cd19 chimeric antigen receptor in piggybac transposon-engineered t cells have strong tumor-killing activity in vitro and therapeutic effects in cell line-derived xenograft models, and no obvious side effects such as neurotoxicity and cytokine storm occurred. therefore, we want to evaluate the safety and clinical effect of anti-cd19 car-t cells in clinical trials.

using piggybac transposon/transposase system to deliver genes into primary human t cells - example expression of cd19 car.cars specific to the human cd19 antigen were used. all cars contained the scfv against human cd19 (clone fmc-63), the third bbz cd28z car consisted of the scfv linked to the intracellular domains of cd28, 4-1bb and cd3z through a cd28 transmembrane domain; subjects with relapsed/refractory cd19-positive b-cell lymphoma or b-all can participate if all eligibility criteria are met. all patients received chemotherapy with fludarabine and cyclophosphamide before the infusion of anti-cd19 car-t cells.. after the infusion, subjects will accept follow-up for side effects and effect of anti-cd19 car-t cells. follow-up : safety and adverse events (safety and tolerability of anti-cd19 car-t cell therapy within 14 days): the number and severity of adverse events, an evaluation of their association with the anti-cd19 car-t cell treatment, and the outcome of the adverse events. possible adverse events include cytokine release syndrome, hypotension, reversible neurotoxicity, hypogammaglobulinemia, etc. ct was used to evaluate b-lymphoma lesions. b-all bone marrow samples were collected by bone marrow aspiration to assess minimal residual disease. flow cytometry was used to detect proportion of t cells, b cells, and nk cells in the blood, and expression of cd3, cd4, cd8, anti-cd19 car to determine the effect of anti-cd19 car-t treatment. plasma levels of the cytokines ifn-gamma, tnf-α, il-2, gm-csf, il-10, and il-6 were also determined. data analysis: overall survival and progress free survival were determined by the kaplan-meier method, using all enrolled patients to determine overall survival. study procedures may be performed while hospitalized.

Eligibility criteria:
inclusion criteria: 1. patients or their legal guardians voluntarily participate and sign the informed consent document; 2. male or female patients aged 18 to 70 years (inclusive); 3. pathologically and histologically confirmed cd19 + b cell tumors; patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; or patients voluntarily choose transfusion of anti-cd19 car-t cells as the first treatment program; 4. b-cell tumors / lymphomas and b-cell acute lymphoblastic leukemia include the following four types:1) b-cell acute lymphoblastic leukemia;2) indolent b-cell lymphomas;3) aggressive b-cell lymphoma; 4) multiple myeloma; 5. subjects: (1) residual lesions remain after treatment and not suitable for hematopoietic stem cell transplantation (auto/allo-hsct); (2) relapse after complement receptor 1 (cr1) and unsuitable for hsct; (3) patients with high risk factors; (4) relapse or no remission after hematopoietic stem cell transplantation or cell immunotherapy. 6. have measurable or evaluable tumor foci; 7. liver, kidney and cardiopulmonary functions meet the following requirements: 1) serum glutamic pyruvic transaminase (alt) and serum glutamic oxaloacetic transaminase (ast) \<3 ×upper limit of normal (uln);2) total bilirubin ≤34.2μmol/l;3) serum creatinine\<220μmol/l;4) baseline oxygen saturation≥95%;5) left ventricular ejection fraction（lvef）≥40%. 8. subjects who did not receive chemotherapy, radiotherapy, immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; relevant toxicity≤1 grade before enrollment (except for low toxicity such as hair loss); 9. peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip; 10. clinical performance status of eastern cancer cooperation group (ecog) score ≤2,expected survival≥3 months; exclusion criteria: 1. pregnant (urine/blood pregnancy test positive) or lactating women; 2. planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion; 3. patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment; 4. active or uncontrollable infection within four weeks prior to enrollment; 5. patients with active hepatitis b/c; 6. hiv-infected patients; 7. severe autoimmune or immunodeficiency disorders; 8. patients are allergic to macromolecule drugs such as antigens or cytokines; 9. subjects participated in other clinical trials within 6 weeks before enrollment; 10. systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); 11. mental illness; 12. drug abuse/addiction; 13. the investigators consider other conditions unsuitable for enrollment.