A Clinical Research of CAR T Cells Targeting CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma

Study Overview
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Brief Summary
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The main purpose of this research is to verify the safety of CD19 targeted chimeric antigen receptor T cells and to determine the proper dosage of CAR T cells infused.

Detailed Description
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Nowadays refractory or relapsed leukemia/lymphoma lacks effective treatment. Innovative therapy is urgently required. Chimeric antigen receptor (CAR)-modified T cells have demonstrated great successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. To design better CAR T cells, we have developed new CD19 CARs. Preclinical studies have demonstrated effective killing of CD19 target cells. In this study, the CD19 CARs, will be evaluated in CD19 positive leukemia/lymphoma patients. The primary goal is to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Official Title
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A Clinical Research of Chimeric Antigen Receptor (CAR) T Cells Targeting CD19 Positive Malignant B-cell Derived Leukemia and Lymphoma

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: Chimeric Antigen Receptor Modified T cells Targeting CD19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory B cell derived acute lymphoblastic leukemia(ALL), chronic lymphocytic leukemia(CLL) and non-hodgkin lymphoma. KPS>60. Life expectancy>3 months. Gender unlimited, age from 4 years to 75 years. Disease progresses but reserves reaction to recent treatments. Patients who have failed at least one line of a standard treatment. No serious mental disorder. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L). No other serious diseases(autoimmune disease, immunodeficiency etc.). No other tumors. Patients volunteer to participate in the research. Exclusion Criteria: HIV affected. Patients are allergic to cytokines. Central nervous system leukemia within 28 days. Uncontrolled active infection. Acute or chronic GVHD. Treated with T cell inhibitor. Pregnancy and nursing females. Other situations we think improper for the research.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Acute Lymphoblastic Leukemia<br>Acute lymphoblastic leukemia treated with chimeric antigen receptor modified T cells targeting CD19. | Biological: Chimeric Antigen Receptor Modified T cells Targeting CD19<br>* T cells modified with CD19 targeted chimeric antigen receptor.<br>|
| Other: Chronic Lymphcytic Leukemia<br>Chronic lymphocytic leukemia with chimeric antigen receptor modified T cells targeting CD19. | Biological: Chimeric Antigen Receptor Modified T cells Targeting CD19<br>* T cells modified with CD19 targeted chimeric antigen receptor.<br>|
| Other: Non-Hodgkin Lymphoma<br>Non-hodgkin lymphoma treated with chimeric antigen receptor modified T cells targeting CD19. | Biological: Chimeric Antigen Receptor Modified T cells Targeting CD19<br>* T cells modified with CD19 targeted chimeric antigen receptor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events of each patient. | Determine the toxicity profile of the CD19 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time of Anti-CD19 CAR T cells in vivo. | To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood. | 3 years | 
| Efficacy of anti-CD19 CAR T cells assessed by the ability of CAR T cells to kill leukemia/lymphoma cells |  | 12 weeks | 
| Maximum tolerated dose (MTD) of CD19 targeted CAR T cells. | To confirm the maximum tolerated dose of CD19 targeted CAR T cells. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, CAR T, Leukemia