Humanized CD19 CAR-T Cells With CRS Suppression Technology for r/r CD19+ Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a single center,randomized ,two-cohorts, open-label ,phase 1/2 study to evaluate the efficacy and safety of T cells expressing humanized CD19 chimeric antigen receptors treatment for relapsed/refractory CD19+ acute lymphoblastic leukemia patients.

Detailed Description
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Relapsed/refractory CD19 + acute lymphoblastic leukemia patients were randomly enrolled in this study to compare the efficacy and safety between two cohorts: 1. Humanized CD19 CAR-T cells； 2. Humanized CD19 CAR-T cells with CRS suppression technology.

Official Title
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Humanized Chimeric Antigen Receptor T Cells Against CD19 With Cytokine Release Syndrome (CRS) Suppression Technology for Refractory/Relapsed CD19+ Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia, CD19 Positive, Relapse, Refractory

Intervention / Treatment
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* Biological: Humanized CD19 CAR-T cells
* Biological: Humanized CD19 CAR-T cells with CRS suppression technology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6 to 65 Voluntary informed consent is given Expected survival ≥12 weeks Relapsed or refractory CD19+ acute leukemia, ineligible for allo-HSCT,or relapse after auto-HSCT Organ function: (1)Left ventricular ejection fractions≥ 0.6 by echocardiography (2)ALT ≤3 times of ULN, or bilirubin <2.0 mg/dl (3)Creatinine < 2 mg/dl and less than 2.5 × normal for age (4)Prothrombin time and activated partial thromboplastin time < 2 times of ULN (5)Arterial oxygen saturation> 92% Karnofsky score ≥ 60 ; No history of combined chemotherapy in the recent 1 month and no immunotherapy in the recent 3 months; Exclusion Criteria: Uncontrolled active infections Active hepatitis B or hepatitis C infection HIV infection History of myocardio infarction in the past 6 months, or history of severe arrhythmia Congenital immunodeficiency Pregnant or lactating women History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis Previous treatment with any gene therapy products

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Cohort 1<br>This cohort will determine the safety and efficacy of humanized CD19 CAR-T cells for CD19+ acute lymphoblastic leukemia | Biological: Humanized CD19 CAR-T cells<br>* Express a Second Generation 4-1BB:humanized CD19 CAR-T cells<br>|
| Experimental: Experimental: Cohort 2<br>This cohort will determine the safety and efficacy of humanized CD19 CAR-T cells with CRS suppression technology for CD19+ acute lymphoblastic leukemia. | Biological: Humanized CD19 CAR-T cells with CRS suppression technology<br>* Express a Second Generation 4-1BB:humanized CD19 CAR-T cells with CRS suppression technology<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of severe CRS | The safety of the humanized CD19 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined | 30 days after infusion of humanized CD19 CAR-T cells | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response of humanized CD19 CAR-T cells treatment who achieve morphology complete remission(CR) and MRD negativity. | The efficacy of the humanized CD19 CAR-T cells infusion will be estimated based on the number of participants who have morphology complete remission(CR) and MRD negativity following the humanized CD19 CAR- T cells infusion | 30 days after infusion of humanized CD19 CAR-T cells | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19+ ,CAR-T, CRS