Autologous CD19 CAR T Cells in Relapsed or Refractory B-cell Lymphoma

Study Overview
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Brief Summary
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This is a single arm, open-label, one center, dose escalation clinical study to determine the safety and efficacy of infusion of autologous T cells expressing CD19-redirected Chimeric Antigen Receptor (CD19 CAR T) in adult patients with relapsed or refractory CD19 positive B-cell lymphoma.

Official Title
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A Safety and Efficacy Study of Autologous T Cells Engineered to Express Chimeric Antigen Receptor Targeting CD19 in Patients With Relapsed or Refractory B-cell Lymphoma

Conditions
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B-cell Lymphoma

Intervention / Treatment
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* Biological: autologous anti-CD19 CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD19+ B cell lymphoma,verified by IHC or flow cytometry. a prior history of at least two standard care of medication. ineligible for allogeneic transplantation or relapsed after transplantation. patients are 18 years older. life expectancy > 3months. ECOG ≤ 2. satisfactory major organ functions: adequate heart function with LVEF≥50%; pulse oximetry of ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl . Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L. women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study. measurable tumors. Exclusion Criteria: using immunosuppressive drugs or systemic steroids within one week of enrollment. active infection. HIV positive. active hepatitis B virus infection or hepatitis C virus infection. breastfeeding or pregnant women. patients refuse to practice birth control during study and one year post study. patients with a prior history of other malignances will be excluded from this study, but patients who have been cured from skin basal cell carcinoma or cervical cancer, or who have had their tumors removed by surgical resection but without further therapies and have more than 5 years of progression-free survival, can be included into the study. currently enrolled in other study. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.

Ages Eligible for Study
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Minimum Age: 18 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: CD19 CAR T cells<br>A standard dose escalation approach aimed to assess the safety and efficacy of autologous anti-CD19 CAR T cells will be applied. | Biological: autologous anti-CD19 CAR T cells<br>* Patients will receive a three-day regimen of chemotherapy consisting of fludarabine and cyclophosphamide aimed to deplete the lymphocytes. Four days after lymphodepletion, patients are intravenously infused autologous anti-CD19 CAR T cells. A prescribed CAR T cell dose will be intravenously infused to patient in a three-day split-dose regimen (day0,30%; day1, 30%; day2, 40%).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response rate of anti-CD19 CAR T cell infusion | Defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on standardized response criteria for malignant lymphoma (Cheson BD, JCO, 2007). | 4 weeks | 
| overall survival rate of patients treated with anti-CD19 CAR T cells |  | 2 years | 
| progression-free survival of patients treated with anti-CD19 CAR T cells |  | 2 years |