a Clinical Research of CD19 and CD22 Targeted Prime CAR-T Cell in Relapsed/Refractory B Cell 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 and CD22 targeted prime CAR-T cells therapy for patients with relapsed/refractory B Cell Lymphoma

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 Cell Lymphomato 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 Cell Lymphoma

Conditions
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B Cell Lymphoma

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; 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 Cell Lymphoma | 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 means of 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 means of 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 Cell 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 and CD22 targeted prime CAR-T treatment in patients with refractory/relapsed B Cell Lymphoma | 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 Cell Lymphoma | 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