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Informed consent is signed by the subject |
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Age 18 to 65 |
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Relapsed or refractory acute lymphoblastic leukemia (ALL). (1) Relapse within 12 months of first remission; (2)a. Without remission after more than 6 weeks of induction chemotherapy or without remission after 2 cycles of induction chemotherapy regimen; c. 2nd or greater Bone Marrow (BM) relapse OR; d. First relapse after chemotherapy, without remission after at least 1 rescue treatment; e. Any BM relapse after autologous or allogeneic stem cell transplantation (SCT) |
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Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months of study entry |
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Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a T315I mutation |
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Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening |
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Eastern cooperative oncology group (ECOG) performance status of 0 to 1 |
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Adequate organ function defined as |
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aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN) |
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Serum alanine aminotransferase (ALT) ≤ 3 upper limit of normal (ULN) |
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Total bilirubin ≤ 2 ULN, except in individuals with Gilbert's syndrome; Note: Patients with Gilbert's syndrome that bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN will be eligible |
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A serum creatinine≤ 1.5 ULN or Creatine removal rate ≥ 60mL/min (Cockcroft and Gault) |
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Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and oxygen saturation > 91% on room air |
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International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN |
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Vascular conditions for apheresis |
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Women of childbearing age have a negative blood / urine pregnancy test within 3 days before apheresis and the CNCT19 infusion. Women of child-bearing potential and all male participants must use highly effective methods of contraception throughout the study and for a period of at least two years after the CNCT19 infusion |
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Active Central Nervous System (CNS) involvement by malignancy
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Isolated extra-medullary disease relapse
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Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded
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Lymphodepleting Chemotherapy prescribed by the protocol
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Tyrosine kinase inhibitors (TKI) and hydroxyurea must be stopped > 72 hours prior to CNCT19 infusion
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The following drugs must be stopped > 1 week prior to CNCT19 infusion: 6-mercaptopurine, 6-thioguanine, methotrexate (<25 mg / m2), cytosine arabinoside (<100 mg / m2 / d), vincristine, asparaginase
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CNS prophylaxis treatment must be stopped > 1 week prior to CNCT19 infusion
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Pegylated-asparaginase must be stopped > 4 weeks prior to CNCT19 infusion
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Radiotherapy before CNCT19 infusion
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Non-CNS site of radiation completed < 2 weeks prior to CNCT19 Infusion; CNS
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directed radiation completed < 8 weeks prior to CNCT19 infusion
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Therapeutic systemic doses of steroids were stopped < 72 hours prior to CNCT19 infusion. However, the following physiological replacement doses of steroids are allowed: < 10 mg/day hydrocortisone or equivalent
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Has received anthracycline/anthraquinone drug treatment exceeding the maximum cumulative dose recommended by the guidelines, estimated by investigators before screening, as follows
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Doxorubicin: 550mg/m2 (radiotherapy or combined medication, <(radiotherapy or combined medication, <350~400 mg/m2)
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Epirubicin: 900~1000 mg/m2 (Adriamycin used, <800 mg/m2)
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Pirarubicin: 950 mg/m2
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Mitoxantrone: 160 mg/m2 (using doxorubicin, <120 mg/m2)
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Daunorubicin: 550 mg/m2
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Has had treatment with any prior CAR-T therapy
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Demethoxydaunorubicin: 290 mg/m2
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Patients with acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks before screening; Patients who have received systemic drug therapy for GVHD within 4 weeks before CNCT19 infusion
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Aclarithromycin: 2000 mg/m2 (Adriamycin used, <800 mg/m2)
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Patients with systemic vasculitis (such as Wegener granulomatosis, nodular polyarteritis, etc.), systemic lupus erythematosus; and active or uncontrolled autoimmune disease (such as Crohns' disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.), primary or secondary immunodeficiency (such as human immunodeficiency virus infection or severe infectious disease)
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Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive, hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of detection, hepatitis C antibody (HCV-Ab) positive, anti-treponemia pallidum antibody (TP-Ab) positive, EBV-DNA, and CMV-DNA copies being more than the lower limit of detection
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Prior malignancy. Patients with Prior malignancy that has been cured for ≥ 5 years or has a low risk of relapse, judged by investigators are excluded
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a. Left Ventricular Ejection Fraction (LVEF) ≤45%; b. III/IV congestive heart failure (NYHA); c. Severe arrhythmia, or clinically significant conduction abnormalities that can be seen on ECG, including QTc interval ≥480ms (QTcB=QT/RR1/2); d. Hypertension that has not been controlled after standard treatment (systolic ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg); e. Unstable angina; f. Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent surgery < 6 months prior to CNCT19 infusion; f. Clinically significant valvular disease; g. Other heart diseases that have been judged by the investigator to be unsuitable for receiving cell therapy
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Clinically significant pleural effusion
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Patients with a history of epilepsy, cerebrovascular ischemia / hemorrhage, cerebellar disease or other active central nervous system diseases
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History of deep vein thrombosis or pulmonary embolism within 6 months of screening
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Known history of hypersensitivity to ingredients used in the drug
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Has had treat with live vaccine within 6 weeks prior to screening
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Patients with active infections in screening
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Life expectancy < 3 months
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Patient in other interventional clinical studies, who received live investigational product, including: Unlisted new drugs within 3 months before CNCT19 injection, marketed drug within 5 half-lives before CNCT19 injection, or who intend to participate in another clinical trial or receive anti-tumor therapy outside the protocol during the entire study
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Patients with other conditions making the patients unsuitable for receiving cell therapy as judged by the investigator
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