Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma

Study Overview
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Brief Summary
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Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.

Detailed Description
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To determine: Primary Outcome Measure: The Overall complete remission rate and one-year survival rate of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is superior to or at least not worse than two kinds of single target treatments in the treatment of CD19+/CD20+ B-cell lymphomas. The risk of cancer recurrence in a year of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is inferior to two kinds of single target treatments. Secondary Outcome Measures: Evaluate the initial effect time, time to disease progression, and life quality improvement of combination transfer compare to single target treatments. Evaluate the safety and tolerability of combination transfer compare to single target treatments by observation of high fever duration in patients and testing related cell factor level in peripheral blood.

Official Title
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Sequential Infusion of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor(CAR) T Cells Against Relapsed and Refractory B-cell Lymphoma

Conditions
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Recurrent or Refractory B Cell Malignancy

Intervention / Treatment
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* Biological: Mixed CD19/CD20 CAR-T Transfer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 Years to 70 Years, Male and female Survival time>12 weeks B cell lymphomas diagnosed by Physical examination,pathological examination,Laboratory tests and imaging tests Chemotherapy failure or recurrent B cell lymphomas Creatinine< 2.5mg/dl Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level Bilirubin<2.0mg/dl Karnofsky Performance Status>50% at the time of screening Adequate pulmonary, renal, hepatic, and cardiac function Fail in autologous or allogenic haemopoietic stem cell transplantation Free of leukocytes removal contraindications Voluntarily join CAR-T clinical trial Understand and sign written informed consent Exclusion Criteria: Pregnant or nursing women or women with pregnancy plan in half a year Any infectious disease (HIV, active tuberculosis, ect.) Active hepatitis B, active hepatitis C infection Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte amplification is below 5 fold with the costimulation of cluster of differentiation 3(CD 3)and cluster of differentiation 8(CD 8) Abnormal vital signs or cannot cooperate with the inspectors mental or psychological disease cannot cooperate with treatment and curative effect evaluation Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2(IL-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: 18 Years
Maximum Age: 70 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixed CD19/CD20 CAR-T Transfer<br>Subjects with CD19+/CD20+ B-cell lymphomas will be infused with CD19-targeting CAR T Cells and CD20-targeting CAR T Cells in one time or in parts | Biological: Mixed CD19/CD20 CAR-T Transfer<br>* Autologous CD19 CAR-T cells and CD20 CAR-T cells with average 1-5*10^6 cells/kg body weight,separately.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall complete remission rate | The complete remission rate will be evaluated by routine methods. | Half a year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The initial effect time | The initial effect time will be recorded. | 1 year | 
| The one-year survival rate | The one-year survival rate will be recorded. | 1 year | 
| The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity) | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | 1 month | 
| The time to disease progression | The time to disease progression will be counted after complete remission. | 1 year | 
| The one-year recurrence | The one-year recurrence will be counted after complete remission. | 1 year | 
| The life quality improvement | The life quality improvement will be evaluated by appetite,sleep,pain and mental state. | 1 year |