CD19 and CD22 Targeted CAR-T Cell Therapy for Relapsed/Refractory B Cell Leukemia and Lymphoma

Study Overview
=================
Brief Summary
-----------------
This is a single arm study to evaluate the efficacy and safety of CD19 and CD22 targeted CAR-T cells therapy for patients with relapsed/refractory B Cell Leukemia and Lymphoma.

Detailed Description
-----------------
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, We launch such a clinical trial using CD19 and CD22 targeted CAR-T cells for patients with relapsed and refractory B Cell Leukemia and Lymphoma to evaluate the efficacy and safety of CD19 and CD22 targeted CAR-T cell therapy.

Official Title
-----------------
Safety and Efficacy of CD19 and CD22 Targeted CAR-T Therapy for Relapsed/Refractory B Cell Leukemia and Lymphoma

Conditions
-----------------
Leukemia, B-cell, Lymphoma, B-Cell

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed written informed consent Diagnose as Relapsed and 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 and 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
-----------------
Minimum Age: 2 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Patients will be be treated with CD19 and CD22 CAR-T cells | Biological: CD19 and CD22 targeted CAR-T cells<br>* A single infusion of CD19 and CD22 CAR-T cells will be administered intravenously<br>|

What is the study measuring?
-----------------
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 CAR-T treatment in patients with relapse/refractory B Cell Leukemia and Lymphoma | The response rate of CD19 and CD22 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 and CD22 CAR-T cells in bone marrow and peripheral blood | In vivo (bone marrow and peripheral blood) rate of CD19 and CD22 CAR-T cells were determined by means of flow cytometry | 2 years | 
| Quantity of CD19 and CD22 CAR copies in bone marrow and peripheral blood | In vivo (bone marrow and peripheral blood) quantity of CD19 and CD22 CAR copies were determined by means of qPCR | 2 years | 
| Cellular kinetics of CD19 and CD22 positive cells in Bone marrow | In vivo (bone marrow) rate and quantity of CD19 and CD22 positive cells were determined by means of flow cytometry | 1 years | 
| Levels of Cytokines in Serum | In vivo (Serum) quantity of cytokines(IL-6、IL-10、TNF-α、CRP) | 3 months | 
| Duration of Response (DOR) of CD19 and CD22 CAR-T treatment in patients with refractory/relapsed 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 and CD22 CAR-T treatment in patients with refractory/relapsed 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 and CD22 CAR-T treatment in patients with refractory/relapsed 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD19, CD22, CAR-T