Humanized CAR-T Therapy for Treatment of B Cell Malignancy

Study Overview
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Brief Summary
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The present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a humanized scFv. All participants will receive autologous chimeric antigen receptor engineered T cells.

Detailed Description
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CD19 has been extensively evaluated as a therapeutic target for recurrent or refractory B cell malignancy by chimeric antigen receptor T cell therapy, the single chain antibody sequence (scFv) against CD19 derived from a mouse hybridoma was widely employed. However, the immunogenicity of the mouse scFv sequence might be one of the reasons that CAR-T cells cannot persist in vivo for long. In present study investigators replace the mouse-derived scFv with a a humanized one and evaluate its safety and efficacy.

Official Title
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Humanized CAR-T Therapy for Treatment of Recurrent or Refractory B Cell Malignancy by Targeting CD19

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Biological: CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥3 at the time of consent Survival time>12 weeks B cell hematological malignancies by pathological examination Chemotherapy failure or recurrent B cell malignancy Creatinine< 2.5mg/dl Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level Karnofsky Performance Status>50% at the time of screening Bilirubin<2.0mg/dl Adequate pulmonary, renal, hepatic, and cardiac function Fail in autologous or allogenic haemopoietic stem cell transplantation Free of leukocytes removal contraindications Exclusion Criteria: Pregnant or nursing women Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening Previous treatment with any gene therapy product Abnormal vital signs Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2 General infection or local severe infection, or other infection that is not controlled Dysfunction in lung, heart, kidney and brain. Severe autoimmune diseases other symptoms that are not applicable for CAR-T

Ages Eligible for Study
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Minimum Age: 3 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: CAR-T<br>In interventional studies, patients enrolled will receive autologous 2nd generation CAR-T cells, which contain a humanized single chain antibody sequence against CD19. | Biological: CAR-T<br>* Patients will be infused with autologous CAR-T infusion in a dose escalating manner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAR-T cells persistence in peripheral blood | The presence of CAR T cells in patients' peripheral blood will be quantified with real time qPCR | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B cell number and immunoglobulins in peripheral blood | The number of B cells and immunoglobulins in peripheral blood will be evaluated by routine methods | 12 months |