cd19/cd20 dual-car-t in b-cell leukemia patients

Conditions: B-cell Leukemia

Summary: this is a single center, single arm, open-label, phase i study to evaluate the safety and efficacy of cd19/cd20 dual-car-t cells in patients with refractory and relapsed b-cell leukemia.

this phase i study is designed as a pilot trial evaluating the safety and efficacy of cd19/cd20 dual-car-t cell therapy in subjects with refractory and relapsed b cell leukemia. subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -5, -4 and -3 followed by infusion of cd19/cd20 dual-car-t cells. safety and efficacy of cd19/cd20 dual-car-t cells therapy will be monitored. the purpose of current study is to determine the clinical efficacy and safety of cd19/cd20 dual-car-t cells therapy in patients with refractory and relapsed b-cell leukemia.

Eligibility criteria:
inclusion criteria: 1. relapsed and refractory b-cell acute malignancies with: * relapsed after competed remission, could not get competed remission after at more than 1 course of chemotherapy (including mrd≥0.1%); * mrd≥0.1% after allogeneic hematopoietic stem cell transplantation(hsct), or recurrence after complete remission or mrd ≥ 0.1% after hsct; * refractory: at least two courses of chemotherapy did not achieve complete remission or mrd ≥ 0.1%; 2. patients must have evaluable evidence of disease, including minimal residual disease (mrd); 3. ph + patients who meet the following criteria can register:failure to tolerate tki or tki treatment failure, or failure to transplant; 4. double positive expression of cd19 / cd20 in b cells; 5. ages 1 to 70 years, including boundary values; 6. ecog score 0-3 points; 7. women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside. 8. patients who voluntarily sign informed consent and are willing to comply with treatment plans. exclusion criteria: 1. patients with organ failure: * heart: nyha heart function grade iv; * liver: grade c that achieves child-turcotte liver function grading; * kidney: kidney failure and uremia; * lung: symptoms of respiratory failure; * brain: a person with a disability; 2. active infections that are difficult to control; 3. human immunodeficiency virus (hiv) positive; 4. liver and kidney function: total bilirubin \> 5 × uln, aspartate aminotransferase (ast) and alanine aminotransferase (alt) \> 5 × uln, serum creatinine clearance rate 60ml / min; 5. gvhd ≥ 2 or anti-gvhd treatment; 6. received allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion; 7. subject received anti-tumor treatment (chemotherapy, mab, or hormone) for less than 1 week; 8. central nervous system white blood that is symptomatic or uncontrolled by systemic chemotherapy and intrathecal chemotherapy (a large number of tumor cells in csf, white blood cell count \>15wbcs/ml); 9. intracranial hypertension or unconsciousness; respiratory failure; diffuse vascular internal coagulation; 10. pregnant or lactating women; 11. the patient does not agree to use effective contraception during the treatment period and for the next 3 months; 12. patients who participate in other clinical studies at the same time; 13. the investigator believes that there are other factors that are not suitable for inclusion or influence the subject's participation or completion of the study.