A Study of GC022 CAR-T Cell Immunotherapy for Relapsed or Refractory B- ALL

Inclusion Criteria:

1. Relapsed or refractory paediatric B-cell ALL 1) 2nd or greater bone marrow (BM)relapse or 2) Relapse after remission for the first time in 12 months or 3) Theinterval between relapse after allogeneic hematopoietic stem cell transplantation andCAR-T cells transfusion≥100 days or 4) Primary refractory as defined by not achievinga CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as definedby not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukaemia or

5. Patients with Philadelphia chromosome positive ALL were eligible if they wereintolerant to or had failed two lines of tyrosine kinase inhibitor (TKI) therapy, orif TKI therapy was contraindicated or 6) Ineligible for allogeneic SCT because of: i.Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimeniii. Lack of suitable donor iv. Prior SCT v. Declined allogeneic SCT as a therapeuticoption after documented discussion, including expected outcomes, about the role of SCTwith a BM transplantation physician not part of the study team

2. For relapsed patients, CD19 tumour expression demonstrated in bone marrow orperipheral blood by flow cytometry within 3 months of study entry

3. Aged 2-70 years

4. Eastern cooperative oncology group (ECOG) performance status of 0 to 2

5. Life expectancy≥12 weeks

6. Adequate organ function defined as:1) Creatinine clearance (as estimated by CockcroftGault) ＞60 mL/min. 2) Serum ALT/AST＜2.5 ULN. 3) Total bilirubin＜1.5 mg/dl, except insubjects with Gilbert's syndrome. 4) Cardiac ejection fraction≥45%, no evidence ofpericardial effusion as determined by an ECHO, and no clinically significant ECGfindings. 5) No clinically significant pleural effusion. 6) Baseline oxygen saturation >92% on room air. 7) pulmonary function: ventilation function is normal or isrestricted mildly.

7. Females of reproductive age must be in non-lactation period. Females of childbearingpotential must have a negative serum or urine pregnancy test. All subjects must usemedical-approved-contraception (such as intrauterine device and contraceptive drugs)during the period of trial and in 6 months after cell transfusion therapy.

8. The subject agree to and sign informed consent form, willing and able to comply withthe planned visit, research, treatment planning, laboratory and other test procedures.

Exclusion Criteria:

1. Isolated extra-medullary disease relapse;

2. Patients with Burkitt's lymphoma/leukaemia;

3. Central nervous system leukemia involved CNS3;

4. Concomitant malignancy other than non-melanoma skin cancer or adequately-treatedcervical carcinoma in situ or prostate cancer (PSA score＜1.0) or adequately-treatedlow grade bladder cancer or surgery-cured ductal carcinoma in situ or diagnosis ofother malignancy exceeds 5 years without relapse or treatment during the 5 years;

5. Concomitant genetic diseases except Down syndrome;

6. Any result of the following virology tests is positive: HIV; HCV; HBsAg; or HBCAbpositive with HBV DNA copies positive(≥ 5×10^2 copies/ml); RPR+TPPA postive;

7. Live vaccine ≤4 weeks prior to apheresis;

8. Presence of grade 2 to 4 graft-versus-host disease (GVHD) after allo-HSCT;

9. The following medications were excluded: 1) Steroids: Therapeutic systemic doses ofsteroids must be stopped >72 hours prior to tisagenlecleucel infusion. However, thefollowing physiological replacement doses of steroids are allowed: <12 mg/m^2/dayhydrocortisone or equivalent; 2) Allogeneic cellular therapy: Any donor lymphocyteinfusions must be completed >6 weeks prior to tisagenlecleucel infusion; 3) GVHDtherapies: Any systemic drug used for GVHD must be stopped >4 weeks prior to infusionto confirm that GVHD recurrence is not observed;

10. Preventive treatments of CNS diseases must be stopped ＞3 days prior to infusion (e.g.,intrathecal injection of methotrexate) 1) Radiotherapy of non-CNS nidus must becompleted ＞2 weeks prior to infusion; 2) CNS stereotactic radiotherapy must becompleted ＞8 weeks prior to infusion;

11. ≥2 grade toxicities related to previous therapy are not relieved, with the exceptionof adverse events without security risk (e.g., alopecia);

12. Known life-threatening allergy, hypersensitivity or intolerance to GC022 cells andadjuvant, including DMSO (see investigator's brochure);

13. Patients with active autoimmune disease (e.g., systemic lupus erythematosus, sjogrensyndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory boweldisease) receive immunosuppressive therapy in 4 weeks before inclusion. thyroidhormone replacement therapy is an exception;

14. For patients that underwent major surgical operation before CAR-T treatment, oranticipated to undergo a major surgical operation during the study process, they needto be fully recovered and clinically stable before inclusion.

15. Participate in other clinical trial and received study drugs ＜28 days prior toinclusion;

16. Concomitant disease that may or severe medical condition that may affect patients'safety, including active viral or bacterial infection, uncontrollable systemic fungalinfection, uncontrollable cardiac disease, hypertension, abuse of psychoactive drugs,et al.

17. Any other condition that may increase subjects' risk or interfere with trial'sresults.