CD19-CART Treatment for ALL

Study Overview
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Brief Summary
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This study aims to evaluate the safety and efficacy of a novel CD19-CART in the treatment of refractory or recurrent ALL.

Detailed Description
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Chimeric antigen receptor T cell (CART) is a kind of engineered immunotherapy by transferring an artificial antigen binding receptor and also intercellular co-stimulating molecules into T cells. This kind of engineered T cells gains the ability to recognize antigen specific tumor cells and initiate the killing process in a HLA-independent way. CD19 is the specific cellular marker of B lineage acute leukemia (B-ALL), thus CD19-CART will be efficient in treating B lineage ALL. The investigators have constructed two kinds of CD19-CART. One is equipped with a murine CD19 scFv (single-chain variable fragmentt), while the other with a humanized scFv. This study aims to evaluate the safety and efficacy of both murine and humanized CD19-CART in treating refractory or recurrent ALL.

Official Title
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Safety and Efficacy Evaluation of CD19-CART Treatment for Refractory or Recurrent ALL

Conditions
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Acute Leukemia

Intervention / Treatment
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* Biological: CD19 CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: previously identified as CD19+ ALL. ALL patients not eligible for allogeneic SCT or relapse after allogeneic SCT. Expected survival >12W. Creatinine < 2.5 mg/dl. Alanine transaminase (ALT)/Aspartate Aminotransferase (AST) < 3x normal Bilirubin <2.0 mg/dl 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. Any uncontrolled active medical disorder that would preclude participation as outlined. HIV infection.

Ages Eligible for Study
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Minimum Age: 6 Years
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Enrolled patients will receive CD19-CART cell immunotherapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19-CART with a murine scFv<br>All enrolled patients in this arm will receive CD19-CART with a murine scFv. | Biological: CD19 CART<br>* Patients will get one course of CART treatment with the dose of 0.5-5*10 6/KgBW.<br>|
| Experimental: humanized CD19-CART<br>All enrolled patients in this arm will receive humanized CD19-CART. | Biological: CD19 CART<br>* Patients will get one course of CART treatment with the dose of 0.5-5*10 6/KgBW.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological assessment | Radiological assessment of the therapeutic effect by systemic or local computed Tomography(CT) or positron emission tomography scan. | Month1 to Month12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of CART immunotherapy | After CAR-T cell infusion,we will observe the potential adverse events, especially Cytokine Release Syndrome (CRS) and neurotoxicity | Day 1 to Week 4 |