Immunotherapy Using Autologous T Cell-Engineered With CD19-specific Chimeric Antigen Receptor for the Treatment of Recurrent /Refractory B Cell Leukemia

Study Overview
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Brief Summary
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Objectives: The purpose of this study is to evaluate the safety and prognosis of New Cluster of Differentiation Antigen 19-chimeric Antigen Receptor T (nCAR19-T) Cells in the treatment of recurrent/refractory B-cell tumor and the Optimal dosage of nCAR19-T cell therapy. Methods: This study designs a novel therapy using nCAR19-T. 20 patients will be enrolled. Cyclophosphamide 500 mg - 2000 mg/m2 (day 2) with or without Fludarabine 30 mg/m2 /day, 4 days (day-6,-5,-4,-3); nCAR19-T transfusion：day 0(5×10※5/kg，1×10※6/kg，3×10※6/kg). According to the National Cancer Institute (NCI) standard (CTCAE), they will be observed 24 weeks long. Follow-up survey after the clinical study: within 1 months, once a week; then once a month for 1 years; and then once a year, a total of 15 years.

Detailed Description
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A total of 20 patients may be enrolled over a period of 1-2 years.

Official Title
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A Clinical Study Using Autologous T Cell Engineered With Chimeric Antigen Receptor Targeting to CD19（Cluster of Differentiation Antigen 19) in Treating Patients With Recurrent /Refractory B Cell Leukemia

Conditions
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Refractory B-Cell Tumor, Recurrent B-Cell Tumor

Intervention / Treatment
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* Biological: CD19-specific chimeric antigen receptor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old, male or female Karnofsky≥60% At least 2 courses of chemotherapy were performed Creatinine is less than 2.5mg/dL;alanine aminotransferase (ALT) / aspartate aminotransferase(AST) less than 3 times of the normal bilirubin is less than 3mg/dL Adequate venous access, isolation, and white blood cell production without other taboos Signed informed consent Patients with fertility are willing to use contraceptive method. At least two months after infusion of T cells Exclusion Criteria: Need to use glucocorticoid therapy Need immunotherapy Creatinine > 2.5mg/dL; ALT / AST > 5 times of the normal; bilirubin > 3mg/dL Forced expiratory volume at one second (FEV1)<2 L,diffusing capacity of the lung for carbon monoxide (DLCO)<40% congestive cardiac failure (III or IV, NYHA); Significant hypotension; Coronary heart disease Can not be controlled; DLCO<40% human immunodeficiency virus (HIV), hepatitis B virus (HBV),hepatitis C virus (HCV) patients Had received gene therapy Significant encephalopathy / new focal neurologic impairment Blood culture positive or radiographic evidence of infection Other drugs, or other biological treatment, chemotherapy or radiotherapy are performed within a month The history of allergic reactions in cell therapy and cetuximab similar compounds.

Ages Eligible for Study
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Minimum Age: 18 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: CD19-specific chimeric antigen receptor<br>After pretreatment, cluster of differentiation antigen 19 (CD19)-specific chimeric antigen receptor will be transfused. | Biological: CD19-specific chimeric antigen receptor<br>* Cyclophosphamide 500 mg - 2000 mg/m2 (day 2) with or without Fludarabine 30 mg/m2 /day, 4 days (day 6, 5, 4, 3); nCAR19-T transfusion：day 0(5×105/kg，1×106/kg，3×106/kg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events and tumor response rate related to study drug |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent B-Cell Tumor, Refractory B-Cell Tumor, New Cluster of Differentiation Antigen 19-chimeric Antigen Receptor T Cells, safety, prognosis