CAR-T Cell Therapy Targeting to CD19 for R/R ALL

Study Overview
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Brief Summary
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Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct a trial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.

Official Title
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CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients With Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia With Failed Remission

Intervention / Treatment
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* Biological: CAR T-cell therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as CD19+ B-cell acute lymphoblastic leukemia; Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation; With an estimated survival of higher than 3 months (according to investigator's judgement); Sufficient organ function: left ventricular ejection fractions≥ 0.5 by echocardiography, creatinine < 1.6 mg/dL, aspartate aminotransferase/aspartate aminotransferase < 3 x upper limit of normal, bilirubin <2.0 mg/dL; Karnofsky performance status ≥ 60 or ECOG ≤ 2. Exclusion Criteria: Intolerant to immunosuppressive chemotherapies; With active infection or other uncontrolled complications; With history of seizure; Active hepatitis B or hepatitis C infection and HIV infection; Pregnant or lactating women, or patients refusing to take effective contraception measures; Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).
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-cell therapy<br>Patients enrolled will receive infusion of CD19-targeting CAR T-cells | Biological: CAR T-cell therapy<br>* Patients enrolled will receive infusion of CD19-targeting CAR T-cells with a target dose of 5 10×10E6/kg of recipient weight, after the preparative regimen consisted of fludarabin (30mg/m2, day -5 to -3) and cyclophosphamide (300mg/m2, day -5 to -3).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission | defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery | 1 month post infusion | 
| Minimal residual disease response | defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection | 1 month post infusion | 
| Cytokine release syndrome | grading according to the criteria proposed by Lee, et al (Blood, 2014, 124: 188-195). This grading system ranges from grade 1 (best) to grade 5 (worst), by measuring related symptoms (such as fever, nausea, fatigue, headache, etc.), oxygen requirement, blood pressure and organ toxicity (referred to CTCAE v4.0 grading) | 1 month post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | calculating from the day of CAR T-cell infusion to death or the end of follow-up | 1 year post infusion | 
| Leukemia-free survival | calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up | 1 year post infusion | 
| Cumulative incidence of relapse | calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up | 1 year post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphoblastic Leukemia, Refractory and relapsed, Chimeric antigen receptor T-cell therapy