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 Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

   1. CR not achieved after standardized chemotherapy;
   2. CR achieved following the first induction, but CR duration is ≤ 12 months;
   3. Ineffectively after first or multiple remedial treatments;
   4. 2 or more recurrences;
4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is﹥5%;
5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
6. Serum albumin ≥ 30g/L, total bilirubin ≤ 25.7umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L, platelet count ≥ 50\*10\^9/L;
7. Echocardiogram (ECHO) shows left ventricular ejection fraction (LVEF) ≥ 50%;
8. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
9. Latest treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatment) must have been completed at least 2 weeks prior to screening;
10. Estimated survival time ≥ 3 months;
11. ECOG performance status 0 to 1;
12. Patients or their legal guardians volunteer to participate in the study and sign the informed 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 cell therapies;
3. Patients with extramedullary lesions;
4. Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/ lymphoma per WHO Classification Criteria;
5. Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome 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, or other severe cardiac diseases within 12 months of enrollment;
8. Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
9. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
10. Central nervous system leukemia (CNS2 or CNS3), resistant to intrathecal injecting of chemotherapeutic drugs, and/or undergoing skull and/or spine radiotherapy; patients with 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 and bacterial pharyngitis), or currently receiving antibiotic therapy by intravenous infusion, or have received antibiotic treatment by intravenous infusion within 1 week before cell infusion. However, prophylactic antibiotic, antiviral and antifungal treatments are allowed;
13. Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
14. History of other primary cancer, except for the following conditions:

    1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
    2. Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
15. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
16. Patients with graft-versus-host disease (GVHD);
17. If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B \> 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;
18. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
19. Women pregnant or lactating, with a pregnancy plan within 6 months, fertile but unable to take medically acceptable contraception measures.