Safety and Efficacy of CD19-Targeted CAR-T Therapy for Relapsed/Refractory CD19+ B Cell Leukemia and Lymphoma

Study Overview
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Brief Summary
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This is a single arm study to evaluate the efficacy and safety of CD19-targeted CAR-T cells therapy for patients with relapsed/refractory CD19+ B Cell Leukemia and Lymphoma.

Detailed Description
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There are limited options for treatment of relapse/refractory CD19+ B Cell Leukemia and Lymphoma. CD19 is expressed on most CD19+ B Cell Leukemia and Lymphoma cells so it is an ideal target for CAR-T. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD19 in patients with relapsed/refractory CD19+ B Cell Leukemia and Lymphoma. The primary goal is safety and efficiency assessment, including adverse events and disease status after treatment.

Official Title
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Safety and Efficacy of CD19-Targeted CAR-T Therapy for Relapsed/Refractory CD19+ B Cell Leukemia and Lymphoma

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphoma, Leukemia, B-Cell

Intervention / Treatment
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* Biological: CD19 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent; Diagnose as relapsed /refractory B Cell Leukemia and Lymphoma, and meet one of the following conditions: Failed to standard chemotherapy regimens; Relapse after complete remission, high-risk and / or refractory patients ; Relapse after hematopoietic stem cell transplantation; For patients with Ph + ALL, the following conditions must be met: those who have received a standard induction chemotherapy regimen and who have not achieved complete remission after TKI treatment or have relapsed after remission (cannot tolerate TKI treatment or have contraindications to TKI treatment or the presence of TKI class) Except for drug resistant patients)； Evidence for cell membrane CD19 expression; All genders, ages: 3 to 75 years； The expect time of survive is above 12 weeks; KPS>60； No serious mental disorders ; Left ventricular ejection fraction ≥50% Sufficient hepatic function defined by ALT/AST≤3 x ULN and bilirubin≤2 x ULN; Sufficient renal function defined by creatinine clearance≤2 x ULN; Sufficient pulmonary function defined by indoor oxygen saturation≥92%; With single or venous blood collection standards, and no other cell collection contraindications; Ability and willingness to adhere to the study visit schedule and all protocol requirements. Exclusion Criteria: Have received CAR-T therapy or other genetically modified cell therapy before screening； Participated in other clinical research within 1 month before screening； Have received the following anti-tumor treatment before screening: Have received chemotherapy, targeted therapy or other experimental drug treatment within 4 weeks, except those who have confirmed disease progression after treatment; Live attenuated vaccine within 4 weeks before screening; Convulsion or stoke within past 6 months; Previous history of other malignancy; Presence of uncontrolled active infection; Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive and peripheral blood HCV RNA titer is higher than the lower limit of detection of the research institution; HIV antibody positive; syphilis primary screening antibody positive; Pregnant or breasting-feeding women; Any situation that investigators regard not suitable for attending in this study or may affect the data analysis.

Ages Eligible for Study
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Minimum Age: 3 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19 CAR-T cells treat<br>Patients will be be treated with CD19 CAR-T cells | Biological: CD19 CAR-T cells<br>* A single infusion of CD19-CAR-T cells will be administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events that related to treatment | Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) | 2 years | 
| The response rate of CD19 CAR-T treatment in patients with relapse/refractory CD19+ B Cell Leukemia and Lymphoma that treatment by CD19 CAR-T cells therapy | The response rate of CD19 CAR-T treatment will be recorded and assessed according to the National Comprehensive Cancer Network Guideline | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of CD19 CAR-T cells in bone marrow and peripheral blood | In vivo (bone marrow and peripheral blood) rate of CD19 CAR-T cells were determined by means of flow cytometry | 2 years | 
| Quantity of CD19 CAR copies in bone marrow and peripheral blood | In vivo (bone marrow and peripheral blood) quantity of CD19 CAR copies were determined by means of qPCR | 2 years | 
| Cellular kinetics of CD19 positive cells in bone marrow | In vivo (bone marrow) rate and quantity of CD19 positive cells were determined by means of flow cytometry | 1 years | 
| Levels of Cytokines in Serum | In vivo (Serum) quantity of cytokines | 3 months | 
| Duration of Response (DOR) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma | DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause (censored) | 2 years | 
| Progress-free survival(PFS) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma | PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression (censored) | 2 years | 
| Overall survival(OS) of CD19 CAR-T treatment in patients with refractory/relapsed CD19+ B Cell Leukemia and Lymphoma | OS will be assessed from the first CAR-T cell infusion to death from any cause (censored) | 2 years | 

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