Leukemia, B-Cell
Conditions
Keywords
immunotherapy, CAR-T, leukemia
Brief 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.
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, 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.
Interventions
a 2nd CAR, CD19 as target protein, 4-1BB as co- stimulator, and optimized the spatial conformation by a suitable hinge & transmembrane domain sequences
Sponsors
Shanghai GeneChem Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 70 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with adverse event | 6 weeks | asverse event is evaluated with CTCAE, version 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with tumor response | 8 weeks | summarize tumor response by overal response rates |
| Detection of transferred T cells in the circulation using quantitative -PCR | 6 weeks | — |
Countries
China
Contacts
Primary ContactJianmin Yang, Doctor
Backup ContactXuejun Yu, Master
Outcome results
None listed