a study to assess cd19-targeted immunotherapy t cells in patients with relapsed or refractory cd19+ b cell leukemia

Conditions: Leukemia, B-Cell

Summary: in the conventional treatment options, b cell leukemia could be treated with chemotherapy drugs or hsct. but chemotherapy could barely cured leukemia. and hsct is often limited by lacking of hla-matched donors, even if those patients who received hsct still could be relapsed. and now, chimeric antigen receptor modified t cell infusion maybe an effective treatment to solve these problems. the investigators use a 2nd car- t with the optimized hinge and transmembrane domain to treat patients with relapsed or refractory b cell leukemia, including relapsed cases after hsct. the purpose of this study is to assess the safety and efficacy of this 2nd car-t cells. at the same time, evaluating the possible and clinical responses of using donor-derived t cells engineered car-t cells. detailed description: this study is being conducted to assess anti-cd19-car-t cells safety and efficacy in treating patients with b cell leukemia. the investigators constructed a 2nd car, cd19 as target protein, 4-1bb as co-stimulator. and optimized the spatial conformation by a suitable hinge \& transmembrane domain sequences. the source of t cells for car-t is from two aspects, one is autologous, the other is donor-derived (only suitable for patients received hsct before and relapsed). the infusion dose is (1-5)×106 car positive t cells/kg, and the specific cells numbers depend on the situation of individual car-t cells preparation.

this study is being conducted to assess anti-cd19-car-t cells safety and efficacy in treating patients with b cell leukemia. the investigators constructed a 2nd car, using cd19 as target, using 4-1bb as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. the source of t cells used to prepare car-t could be either autologous, or donor-derived (only suitable for patients received hsct before and relapsed). the infusion dose is (1-5)×106 car positive t cells/kg, and the specific cells numbers depends on the situation of individual car-t cells preparation.

Eligibility criteria:
inclusion criteria: * patients with cd19+ b-cell leukemia as comfirmed by flow cytometry * age: 1-70 years old * expected survival \> 12 weeks * creatinine \< 2.5 mg/dl * alt/ast \< 3x normal * bilirubin \<2.0 mg/dl * sucessful test expansion of t-cells * adequate venous access for apheresis, and no other contraindications for leukapheresis * voluntary informed consent is given exclusion criteria: * pregnant or lactating women * uncontrolled active infection * active hepatitis b or hepatitis c infection * concurrent use of systemic steroids. recent or current use of inhaled steroids is not exclusionary * previously treatment with any gene therapy products * feasibility assessment during screening demonstrates\<30% transduction of target lymphocytes, or insufficient expansion (\<5-fold) in response to cd3/cd28 costimulation * active central nervous system leukemia * any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade ш or ⅳ cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases)

Keywords: immunotherapy car-t leukemia