CTA101 UCAR-T Cell Injection for Treatment of Relapsed or Refractory CD19+ B-cell Acute Lymphoblastic Leukemia

Inclusion Criteria:

1. Male or female aged 3-70 years old;

2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National ComprehensiveCancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);

3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

4. CR not achieved after standardized chemotherapy;

5. CR achieved following the first induction, but CR duration is ≤ 12 months;

6. Ineffectively after first or multiple remedial treatments;

7. 2 or more recurrences;

8. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5%;

9. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKItreatments;

10. Serum albumin ≥ 30g/L, total bilirubin ≤ 25.7umol/L, ALT and AST ≤ 3 times of upperlimit of normal, creatinine ≤ 176.8umol/L, platelet count ≥ 50*10^9/L;

11. Echocardiogram (ECHO) shows left ventricular ejection fraction (LVEF) ≥ 50%;

12. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;

13. Latest treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or othertreatment) must have been completed at least 2 weeks prior to screening;

14. Estimated survival time ≥ 3 months;

15. ECOG performance status 0 to 1;

16. Patients or their legal guardians volunteer to participate in the study and sign theinformed consent.

Exclusion Criteria:

1. History of hypersensitivity to any component of cell product;

2. Prior treatment with any CAR T cell product or other genetically-modified T celltherapies;

3. Patients with extramedullary lesions;

4. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt'sleukemia/ lymphoma per WHO Classification Criteria;

5. Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachmansyndrome or any other known bone marrow failure syndrome;

6. Patients with New York Heart Associate (NYHA) Class III/IV cardiac insufficiency;

7. Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, orother severe cardiac diseases within 12 months of enrollment;

8. Severe primary or secondary hypertension of grade 3 or above (WHO HypertensionGuidelines, 1999);

9. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascularischemia, and cerebrovascular hemorrhagic diseases;

10. Central nervous system leukemia (CNS2 or CNS3), resistant to intrathecal injecting ofchemotherapeutic drugs, and/or undergoing skull and/or spine radiotherapy; patientswith history of CNS but effectively controlled to allow enrollment;

11. Prior treatment with TKIs (Ph+ ALL) 1 week prior to enrollment;

12. Patients with severe active infections (excluding simple urinary tract infection andbacterial pharyngitis), or currently receiving antibiotic therapy by intravenousinfusion, or have received antibiotic treatment by intravenous infusion within 1 weekbefore cell infusion. However, prophylactic antibiotic, antiviral and antifungaltreatments are allowed;

13. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile ductcatheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicatedcentral venous access catheters such as Port-a-Cath or Hickman catheters are allowed;

14. History of other primary cancer, except for the following conditions:

15. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;

16. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ withdisease-free survival ≥ 2 years after adequate treatment;

17. Patients with autoimmune diseases requiring treatment, patients with immunodeficiencyor requiring immunosuppressive therapy;

18. Patients with graft-versus-host disease (GVHD);

19. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients withactive hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy isrequired after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;

20. Concurrent therapy with systemic steroids within 1 week prior to screening, except forthe patients recently or currently receiving inhaled steroids;

21. Women pregnant or lactating, with a pregnancy plan within 6 months, fertile but unableto take medically acceptable contraception measures.