|
|
Informed consent is signed by the subject |
|
|
|
|
Age 18 to 65 |
|
|
|
|
Relapsed or refractory ALL |
|
|
|
|
|
Relapse within 12 months of first remission |
|
|
|
|
Without remission after more than 6 weeks of induction chemotherapy or without remission after 2 cycles of induction chemotherapy regimen |
|
|
|
|
|
2nd or greater Bone Marrow (BM) relapse OR |
|
|
|
|
|
First relapse after chemotherapy, without remission after at least 1 rescue treatment |
|
|
|
|
|
Any BM relapse after autologous stem cell transplantation (SCT) |
|
|
|
|
|
Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months of study entry |
|
|
|
|
|
Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 1 generation and/or 2 generation of tyrosine kinase inhibitor therapy (TKI); no TKI salvage treatments if the patient has a T315I mutation |
|
|
|
|
Bone marrow with 5% lymphoblasts by morphologic assessment at screening |
|
|
|
|
|
Eastern cooperative oncology group (ECOG) performance status of 0 to 1 |
|
|
|
|
|
Adequate organ function defined as |
|
|
|
|
|
aspartate aminotransferase (AST) 3 upper limit of normal (ULN) |
|
|
|
|
|
Serum alanine aminotransferase (ALT) 3 upper limit of normal (ULN) |
|
|
|
|
|
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 |
|
|
|
|
|
A serum creatinine 1.5 ULN or Creatine removal rate 60mL/min (Cockcroft and Gault) |
|
|
|
|
|
Must have a minimum level of pulmonary reserve as Grade 1 dyspnea and oxygen saturation > 91% on room air |
|
|
|
|
|
International normalized ratio (INR) 1.5 ULN and activated partial thromboplastin time (APTT) 1.5 ULN |
|
|
|
|
|
Have appropriate vascular conditions for apheresis |
|
|
|
|
|
Non-hematological toxic reactions (excluding diseases related) caused by previous treatment were restored to 1 level before screening (excluding 2 level of neurotoxicity caused by hair loss and chemotherapy drugs) |
|
|
|
|
|
Women of childbearing age have a negative blood / urine pregnancy test within 7 days before 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 six months after the CNCT19 infusion |
|
|
|
|
|
Active CNS involvement by malignancy
|
|
|
|
|
|
Isolated extra-medullary disease relapse
|
|
|
|
|
|
Patients who received chemotherapy within 2 weeks before CNCT19 infusion. The following situations are excluded
|
|
|
|
|
|
Lymphodepleting Chemotherapy prescribed by the protocol
|
|
|
|
|
|
Tyrosine kinase inhibitors (TKI) and hydroxyurea must be stopped > 72 hours prior to CNCT19 infusion
|
|
|
|
|
|
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
|
|
|
|
|
|
Pegylated-asparaginase must be stopped > 4 weeks prior to CNCT19 infusion
|
|
|
|
|
|
CNS prophylaxis treatment must be stopped > 1 week prior to CNCT19 infusion
|
|
|
|
|
|
Radiotherapy before CNCT19 infusion
|
|
|
|
|
|
Non-CNS site of radiation completed < 2 weeks prior to CNCT19 infusion; CNS
|
|
|
|
|
|
directed radiation completed < 8 weeks prior to CNCT19 infusion
|
|
|
|
|
|
\. 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
|
|
|
|
|
|
\. Has had treatment with any prior CAR-T therapy
|
|
|
|
|
|
\. Patients who have previously received allogeneic hematopoietic stem cell
|
|
|
|
|
|
transplantation (allo-HSCT)
|
|
|
|
|
|
\. Patients with systemic vasculitis (such as Wegener granulomatosis, nodular
|
|
|
|
|
|
polyarteritis, systemic lupus erythematosus) and active or uncontrolled
|
|
|
|
|
|
autoimmune disease (such as autoimmune hemolytic anemia, etc.)
|
|
|
|
|
|
\. Patients who are positive for any of HBsAg, HBeAg, HBeAb, HBcAb, HCV-Ab
|
|
|
|
|
|
TP-Ab
|
|
|
|
|
|
\. Active malignancy. Patients with Prior malignancy that has been cured for
|
|
|
|
|
|
years are excluded
|
|
|
|
|
|
\. a. Left Ventricular Ejection Fraction (LVEF) 45%; b. III/IV congestive
|
|
|
|
|
|
heart failure (NYHA); c. Severe arrhythmia ; QTc450ms (male)or QTc470ms
|
|
|
|
|
|
(female)(QTcB=QT/RR1/2); d.Uncontrolled hypertension (systolic blood pressure
|
|
|
|
|
|
mmHg and / or diastolic blood pressure 90 mmHg) or pulmonary hypertension
|
|
|
|
|
|
or unstable angina; e. 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
|
|
|
|
|
|
\. Clinically significant pleural effusion
|
|
|
|
|
|
\. Patients with a history of epilepsy, cerebrovascular ischemia
|
|
|
|
|
|
hemorrhage, cerebellar disease or other active central nervous system
|
|
|
|
|
|
diseases
|
|
|
|
|
|
\. History of deep vein thrombosis or pulmonary embolism within 6 months of
|
|
|
|
|
|
screening
|
|
|
|
|
\. Known history of hypersensitivity to ingredients used in the drug
|
|
|
|
|
|
\. Has had treat with live vaccine within 6 weeks prior to screening
|
|
|
|
|
|
\. Patients with evidence of currently uncontrollable serious active
|
|
|
|
|
|
infections (e.g., sepsis, bacteremia, fungemia, viremia, etc.)
|
|
|
|
|
|
\. Life expectancy < 3 months
|
|
|
|
|
|
\. Patient in other interventional clinical studies within 3 months before
|
|
|
|
|
|
screening, who have received active drug therapy, or who intend to participate
|
|
|
|
|
|
in another clinical trial or receive anti-tumor therapy outside the protocol
|
|
|
|
|
|
during the entire study
|
|
|
|
|
|
\. Patients with other conditions making the patients unsuitable for
|
|
|
|
|
|
receiving cell therapy as judged by the investigator
|
|
|
|