A Study to Assess CD19-targeted Immunotherapy T Cells in Patients With Relapsed or Refractory CD19+ B Cell Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With Relapsed or Refractory CD19+ B Cell Leukemia

Conditions
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Leukemia, B-Cell

Intervention / Treatment
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* Drug: anti-CD19-CAR-T cells


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-CD19-CAR-T cells<br>patients receive chemotherapy(CF, cyclophosphamide and Fludarabine) on day -6 to day -1, then infusied with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity. | Drug: anti-CD19-CAR-T cells<br>* a 2nd CAR, CD19 as target protein, 4-1BB as co- stimulator, and optimized the spatial conformation by a suitable hinge & transmembrane domain sequences<br>* Other names: 2nd CAR-T;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse event | asverse event is evaluated with CTCAE, version 4.0 | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with tumor response | summarize tumor response by overal response rates | 8 weeks | 
| Detection of transferred T cells in the circulation using quantitative -PCR |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, CAR-T, leukemia