CD19/CD20 Dual-CAR-T in B-cell Leukemia Patients

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.

Inclusion criteria

• 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%;
• Patients must have evaluable evidence of disease, including minimal residual disease (MRD);
• Ph + patients who meet the following criteria can register:Failure to tolerate TKI or TKI treatment failure, or failure to transplant;
• Double positive expression of CD19 / CD20 in B cells;
• Ages 1 to 70 years, including boundary values;
• ECOG score 0-3 points;
• 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.
• Patients who voluntarily sign informed consent and are willing to comply with treatment plans.

Exclusion criteria

• 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;
• Active infections that are difficult to control;
• Human immunodeficiency virus (HIV) positive;
• Liver and kidney function: total bilirubin > 5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 5 × ULN, serum creatinine clearance rate 60mL / min;
• GVHD ≥ 2 or anti-GVHD treatment;
• Received allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion;
• Subject received anti-tumor treatment (chemotherapy, mAb, or hormone) for less than 1 week;
• 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);
• intracranial hypertension or unconsciousness; respiratory failure; diffuse vascular internal coagulation;
• pregnant or lactating women;
• The patient does not agree to use effective contraception during the treatment period and for the next 3 months;
• Patients who participate in other clinical studies at the same time;
• 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.