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The subject or her/his legally guardian(s) must sign the informed consent form approved by the Institutional Ethics Committee (IEC) prior to any screening procedures |
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Subjects aged 18 years or older with relapsed or refractory DLBCL (primary mediastinal large B-cell lymphoma and transformed follicular lymphoma included), of which refractory is defined as |
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Have no response to the recent treatment including |
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The best response to the treatment regimen is progressive disease (PD) ,or |
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stable disease (SD) which maintained less than 6 months after the last treatment, or |
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not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including |
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progressive disease after ASCT or relapse within 12 months (relapse must be confirmed by biopsy), or |
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If remedial treatment is given after ASCT, the subject must have no response or relapse after the last treatment. 3\. Subjects who have previously received 2 lines treatment, and at least including |
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Anti-CD20 monoclonal antibody(rituximab), unless the CD20 negative |
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A chemotherapy regimen containing anthracyclines |
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The DLBCL patients who transformed from follicular lymphoma must have previously received chemotherapy for follicular lymphoma and have developed chemotherapy-refractory diseases after transform to DLBCL. 4\. Confirmation for either CD19 or CD20 positivity using immunohistochemistry or flow cytometry; 5\. According to the initial evaluation, staging and response assessment of Hodgkin's and non-Hodgkin's lymphoma -the Lugano Classification (2014), there is at least one measurable lesion at baseline; 6\. Life expectancy 12 weeks; 7\. Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening; 8\. Adequate organ function |
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Renal function defined as |
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A serum creatinine of 1.5 Upper Limit of Normal (ULN), or |
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Estimated Glomerular Filtration Rate (eGFR) 60 ml/min/1.73m2 |
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Liver function defined as |
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ALT 5 Upper Limit of Normal (ULN) for age, and |
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Total bilirubin 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is 3.0 ULN and direct bilirubin 1.5 ULN |
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Must have a minimum level of pulmonary reserve defined as Grade 1 dyspnea and |
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blood oxygen saturation > 91% on room air |
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\. Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) 45% |
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confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA) |
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\. Adequate bone marrow reserve without transfusions defined as |
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Absolute neutrophil count (ANC) >110^9 /L |
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Absolute lymphocyte count (ALC) 0.310^9 /L |
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Platelets 5010^9 /L |
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Hemoglobin > 8.0 g/dl; 11\. Must have an apheresis product of non-mobilized cells or peripheral blood harvested cells accepted for manufacturing 12\. Subjects who use the following drugs should meet the following criteria |
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Steroids: Therapeutic doses of steroids must be stopped 2 weeks prior to A-02 infusion. However, the following physiological replacement doses of steroids are allowed: < 6 - 12 mg/m^2/day hydrocortisone or equivalent |
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Immunosuppression: Any immunosuppressive medication must be stopped 4 weeks prior to sign the informed consent form |
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Anti-proliferative therapy other than pretreatment chemotherapy within 2 weeks of A-02 infusion |
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CD20 antibody-related treatment must be discontinued within 4 weeks of A-02 infusion or 5 half-lives (whichever is longer) |
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CNS disease prophylaxis must be stopped > 1 week prior to A-02 infusion (e.g. intrathecal methotrexate); 13\. The investigator judged that the subject recovered from the toxicity of the previous anti-tumor treatment to grade 1 or below (except for special grade 2 or below toxicity that cannot be recovered in a short period of time, such as hair loss), suitable for pretreatment. Chemotherapy and treatment of CAR-T cells; 14\. Women of child-bearing potential and all male subjects must agree to use highly effective methods of contraception for at least 12 months following A-02 infusion and until CAR-T cells are no longer present by PCR on two consecutive tests |
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Prior treatment with any cell therapy before signing the informed consent form, including CAR-T therapy
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Subjects with detectable cerebrospinal fluid malignant cells or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma
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Subjects with testicular invasion, including those who have had testicular resection
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Subjects with current or previous history of central nervous system disease, such as seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system
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Subjects who have previously received allogeneic hematopoietic stem cell transplantation (HSCT); or suitable and consenting to Autologous hematopoietic stem cell transplantation (ASCT)
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Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of A-02 infusion
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Patients on oral anticoagulation therapy within 1 week of A-02 infusion
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Prior radiation therapy within 2 weeks of A-02 infusion
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Investigational medicinal product within the last 30 days prior to sign the informed consent form
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Subjects with active hepatitis Bdefined as hepatitis B surface antigen positive, or hepatitis B core antibody positive with hepatitis B virus DNA detection value > 1000 copies/mlor hepatitis C (HCV RNA positive)
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Subjects positive for HIV antibody or treponema pallidum antibody
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Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive 72 hours prior to A-02 infusion)
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Unstable angina and/or myocardial infarction within 6 months prior to sign the informed consent form
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Previous or concurrent malignancy with the following exceptions
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Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to sign the informed consent form)
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In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to sign the informed consent form
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A primary malignancy which has been completely resected and in complete remission for 5 years
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Pregnant or nursing women (women of childbearing age were tested positive for pregnancy during screening period)
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Cardiac arrhythmia not controlled with medical management
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Subjects with active neurological auto immune or inflammatory disorders (e.g. Guillain Barre Syndrome, Amyotrophic Lateral Sclerosis)
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Other conditions that the investigator thinks he/she should not be included in this clinical trial, such as poor compliance
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