CD19-directed CAR T Cells Therapy in Relapsed/Refractory B Cell Malignancy

Study Overview
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Brief Summary
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Relapsed/refractory leukemia and lymphoma lack effective treatment. The cancer immunotherapy with chimeric antigen receptor (CAR) T cells provides a potent new approach for them. In this clinical trial, the investigators aim to assess the safety and efficacy of administering T cell expressing an anti-CD19 CARs to patients with chemotherapy resistant or refractory CD19 positive B cell malignancy including leukemia and lymphoma.

Detailed Description
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Tongji Hospital of Tongji University has developed an investigational approach for treating patients with CD19 positive B cell malignancy that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with lentivirus to attack CD19 positive cells, and then giving the cells back to the patients.The main purpose of the study is to assess the safety and efficacy of the treatment with anti-CD19 CAR-T cells in the patients with chemotherapy resistant or refractory CD19 positive B cell malignancy including leukemia and lymphoma.

Official Title
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CD19-directed Chimeric Antigen Receptor T Cells Therapy in Relapsed/Refractory B Cell Malignancy

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: CD19-directed CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CD19+ leukemia or lymphoma, meeting the following criteria: At least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Rituximab) therapy) Less than 1 year between last chemotherapy and progression Not eligible or appropriate for allo-HSCT To be aged 6 to 85 years Estimated survival of ≥ 6 months, but ≤ 2 years ECOG score ≤2 Relapse after auto-HSCT Women of childbearing potential must have a urine pregnancy test taken and proven negative prior to the treatment. All patients agree to use reliable methods of contraception during the trial period and until follow-up for the last time Voluntary participation in the clinical trials and sign the informed consent Exclusion Criteria: History of epilepsy or other CNS disease Patients have GVHD, which needs treatment with immunosuppressive agents Patients with prolonged QT interval or severe heart disease Patients in pregnancy or breast-feeding period 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 <20% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation ALT /AST>3 x normal value; Creatinine> 2.5 mg/dl; Bilirubin >2.0 mg/dl Any uncontrolled medical disorders that the researchers consider are not eligible to participate the clinical trial HIV infection Any situation that would increase dangerousness of subjects or disturb the outcome of the clinical study according to the researcher's evaluation

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 85 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: CAR-T cells<br>Autologous 2nd generation CD19-directed CAR-T cells | Biological: CD19-directed CAR-T cells<br>* CD19-directed CAR-T cell infusion will be given by vein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of study related adverse events | defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly，likely，or definitely related to the study. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates to CAR-T cells | Describe the response rates of patients treated with CAR-T cells, including complete remission, partial remission,stable disease and progression disease | 2 years | 
| Progression free survival(PFS) |  | 2 years | 
| Duration of remission(DOR) |  | 2 years | 
| Overall survival(OS) of patients treated with CAR-T cells |  | 2 years |