| Eligibility |
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) The
interval between relapse after allogeneic hematopoietic stem cell transplantation and
CAR-T cells transfusion=100 days or 4) Primary refractory as defined by not achieving
a CR after 2 cycles of a standard chemotherapy regimen or chemorefractory as defined
by 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 were
intolerant to or had failed two lines of tyrosine kinase inhibitor (TKI) therapy, or
if TKI therapy was contraindicated or 6) Ineligible for allogeneic SCT because of: i.
Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimen
iii. Lack of suitable donor iv. Prior SCT v. Declined allogeneic SCT as a therapeutic
option after documented discussion, including expected outcomes, about the role of SCT
with a BM transplantation physician not part of the study team
2. For relapsed patients, CD19 tumour expression demonstrated in bone marrow or
peripheral 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 Cockcroft
Gault) >60 mL/min. 2) Serum ALT/AST<2.5 ULN. 3) Total bilirubin<1.5 mg/dl, except in
subjects with Gilbert's syndrome. 4) Cardiac ejection fraction=45%, no evidence of
pericardial effusion as determined by an ECHO, and no clinically significant ECG
findings. 5) No clinically significant pleural effusion. 6) Baseline oxygen saturation
>92% on room air. 7) pulmonary function: ventilation function is normal or is
restricted mildly.
7. Females of reproductive age must be in non-lactation period. Females of childbearing
potential must have a negative serum or urine pregnancy test. All subjects must use
medical-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 with
the 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-treated
cervical carcinoma in situ or prostate cancer (PSA score<1.0) or adequately-treated
low grade bladder cancer or surgery-cured ductal carcinoma in situ or diagnosis of
other 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 HBCAb
positive with HBV DNA copies positive(= 5×10^2 copies/ml); RPR+TPPA postive;
7. Live vaccine =4 weeks prior to apheresis;
8. Prior CD19 targeted therapy with the exception of subjects who received GC007F in this
study and are eligible for re-treatment; Prior chimeric antigen receptor therapy or
other genetically modified T cell therapy;
9. Presence of grade 2 to 4 graft-versus-host disease (GVHD) after allo-HSCT;
10. The following medications were excluded: 1) Steroids: Therapeutic systemic doses of
steroids must be stopped >72 hours prior to tisagenlecleucel infusion. However, the
following physiological replacement doses of steroids are allowed: <12 mg/m^2/day
hydrocortisone or equivalent; 2) Allogeneic cellular therapy: Any donor lymphocyte
infusions must be completed >6 weeks prior to cell infusion; 3) GVHD therapies: Any
systemic drug used for GVHD must be stopped >4 weeks prior to infusion to confirm that
GVHD recurrence is not observed;
11. Prior treatments of CNS diseases must be stoped >3 days prior to infusion (e.g.,
intrathecal injection of methotrexate) 1) Radiotherapy of non-CNS nidus must be
completed >2 weeks prior to infusion; 2) CNS stereotactic radiotherapy must be
completed >8 weeks prior to infusion;
12. =2 grade toxicities related to previous therapy are not relieved, with the exception
of adverse events without safety risk (e.g., alopecia);
13. Known life-threatening allergy, hypersensitivity or intolerance to GC007F cells and
adjuvant, including DMSO (see investigator's brochure);
14. Patients with active autoimmune disease (e.g., systemic lupus erythematosus, sjogren
syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel
disease) receive immunosuppressive therapy in 4 weeks before inclusion. thyroid
hormone replacement therapy is an exception;
15. For patients that underwent major surgical operation before CAR-T treatment, or
anticipated to undergo a major surgical operation during the study process, they need
to be fully recovered and clinically stable before inclusion.
16. Participate in other clinical trial and received study drugs <28 days prior to
inclusion;
17. Concomitant disease that may or severe medical condition that may affect patients'
safety, including active viral or bacterial infection, uncontrollable systemic fungal
infection, uncontrollable cardiac disease, hypertension, abuse of psychoactive drugs,
et al.
18. Any other condition that may increase subjects' risk or interfere with trial's
results.
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