a Clinical Research of CD19 and CD22 Targeted Prime CAR-T Cell in Relapsed/Refractory B-ALL

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 and CD22 targeted prime CAR-T cells therapy for patients with relapsed/refractory B -ALL

Detailed Description
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Although the anti-CD19 CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell hematologic malignancies. There are patients who resisted anti-CD19 CAR-T cells or with CD19 negative relapse. To make further improvement, the investigators launch such a clinical trial using CD19 and CD22 targeted prime CAR-T cells for patients with relapsed and refractory B-ALL to evaluate the efficacy and safety of CD19 and CD22 targeted prime CAR-T cell therapy.

Official Title
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Study Evaluating Safety and Efficacy of CD19 and CD22 Targeted Prime CAR-T Cell in Patients With Relapsed/Refractory B-ALL

Conditions
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B-ALL

Intervention / Treatment
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* Biological: CD19 and CD22 targeted prime CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Diagnose as Relapsed and Refractory B -ALL, 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 or CD22 expression All genders ages: 2 to 75 years The expect time of survive is above 3 months; 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: Previous history of other malignancy; Presence of uncontrolled active infection; Evidence of disorder that need the treatment by glucocorticoids; Active or chronic GVHD The patients treatment by inhibitor of T cell Pregnant or breasting-feeding women; Any situation that investigators regard not suitable for attending in this study (e.g. HIV , HCVinfection or intravenous drug addiction) or may affect the data analysis.

Ages Eligible for Study
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Minimum Age: 2 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: prime CAR- T cells<br>Patients will be be treated with CD19 and CD22 prime CAR- T cells | Biological: CD19 and CD22 targeted prime CAR-T cells<br>* A single infusion of CD19 and CD22 prime 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 and CD22 prime CAR-T treatment in patients with relapse/refractory B-ALL | The response rate of CD19 and CD22 prime 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 prime CAR-T cells in bone marrow | Determine the rate of prime CAR-T cells in bone marrow by flow cytometry | 2 years | 
| Rate of prime CAR-T cells in peripheral blood | Determine the rate of prime CAR-T cells in peripheral blood by flow cytometry | 2 years | 
| Quantity of prime CAR copies in bone marrow | Determine the quantity of prime CAR copies in bone marrow by qPCR | 2 years | 
| Quantity of prime CAR copies in peripheral blood | Determine the quantity of prime CAR copies in peripheral blood by qPCR | 2 years | 
| Rate of CD19 and CD22 positive cells in Bone marrow | Determine the rate of CD19 and CD22 positive cells in bone marrow by flow cytometry | 1 years | 
| Levels of IL-6 in Serum | Serological determination of IL-6 | 3 months | 
| Levels of IL-10 in Serum | Serological determination of IL-10 | 3 months | 
| Levels of TNF-α in Serum | Serological determination of TNF-α | 3 months | 
| Levels of CRP in Serum | Serological determination of CRP | 3 months | 
| Duration of Response (DOR) of CD19 and CD22 prime CAR-T treatment in patients with refractory/relapsed B-ALL | 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 and CD22 targeted prime CAR-T treatment in patients with refractory/relapsed B-ALL | PFS will be assessed from the first prime CAR-T cell infusion to death from any cause or the first assessment of progression (censored) | 2 years | 
| Overall survival(OS) of CD19 and CD22 prime CAR-T treatment in patients with refractory/relapsed B-ALL | OS will be assessed from the first primeCAR-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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CD19, CD22, CAR-T