Anti-CD22 CAR-T Cell Therapy Targeting B Cell Malignancies

Study Overview
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Brief Summary
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The study will evaluate safety and efficacy of the CD22-targeted chimeric antigen receptor modified-T cell(CAR-T) cells in the treatment of B-cell Malignancies.

Detailed Description
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Clinical success with chimeric antigen receptor (CAR)- based immunotherapy for leukemia has been accompanied by the associated finding that antigen-escape variants of the disease are responsible for relapse. Despite anti-CD19 CAR-T exhibited the ability to re-induce remissions for many patients with relapsed and refractory B cell malignancies, a part of those patients will relapse with CD19-negative malignancies. CD22 is a type I transmembrane protein expressed on most mature B lymphocyte in the B cell malignancies，and plays a significant role in signal transduction pathway. The investigators design and conduct this trial to test the safety and effectiveness of CD22-targeted CAR-T.

Official Title
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Anti-CD22 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy Targeting CD22 in Treating Patients With B Cell Malignancies

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: Anti-CD22-CAR-transduced T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-65 years Patients with Cluster of Differentiation 22(CD22) positive B cell malignancies as confirmed by flow cytometry Refractory or relapsed B cell-acute lymphoblastic leukemia No available curative treatment options (such as hematopoietic stem cell transplantation) Stage III-IV disease Creatinine < 2.5 mg/dl Aspartate transaminase-alanine transaminase ratio < 3x normal Bilirubin < 2.0 mg/dl Karnofsky performance status >= 60 Expected survival time > 3 months Adequate venous access for apheresis Ability to understand and provide informed consent Exclusion Criteria: Pregnant or lactating women Patients requiring T cell immunosuppressive therapy Active central nervous system leukemia Any concurrent active malignancies Patients with a history of a seizure disorder or cardiac disorder Previous treatment with any immunotherapy products Patients with human immunodeficiency virus, hepatitis B or C infection Uncontrolled active infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: anti-CD22 CAR-T<br>Patients will receive a full dose CART infusion at day 0. | Biological: Anti-CD22-CAR-transduced T cells<br>* a single dose of Anti-CD22-CAR-transduced T cells will be infusion after preconditioning.<br>* Other names: anti-CD22 CART, CART22;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events related to treatment as assessed by NCI CTCAE version 4.03 |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Complete Remission Rate (ORR) |  | 2 years | 
| Disease response(CR, CRi) |  | 2 years | 
| CART cells persistence in vivo |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Lymphoma, CD22, CAR-T