| Eligibility |
Inclusion Criteria:
1. Aged 18-70 years;
2. Eastern cooperative oncology group (ECOG) performance status of 0 to 2;
3. Life expectancy=12 weeks;
4. CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow
cytometry;
5. Relapsed or refractory B- ALL: a) Refractory B- ALL: Fail to achieve a CR after 2
cycles of a standard induction chemotherapy regimen or one-line/multi-line salvage
chemotherapy; b) Relapsed B- ALL: Relapse after remission for the first time in 12
months or relapse after one-line/multi-line salvage chemotherapy; Relapse is defined
as recurrence of primitive cell in peripheral blood or bone marrow(>5%) after
remission; c)Relapse after autologous stem cell transplantation or allogeneic
hematopoietic stem cell transplantation; d)Patients with Philadelphia chromosome
positive(Ph+) ALL were eligible if they were intolerant to or had failed two lines of
tyrosine kinase inhibitor (TKI) therapy, or had t315i mutation.
6. Did not receive hematopoietic stem cell transplantation=6 months prior to enrollment;
7. Adequate organ function defined as: a) Creatinine clearance (as estimated by Cockcroft
Gault method) >60 mL/min; b) Serum ALT/AST <2.5 ULN; c) Total bilirubin <1.5 ULN
(subjects with Gilbert's syndrome=3 ULN); d) Cardiac ejection fraction=50%, no
evidence of clinically significant pericardial effusion as determined by an ECHO; e)
No clinically significant pleural effusion; f) Baseline oxygen saturation >92% on room
air;
8. 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 treatment and in 2 years after cell transfusion treatment; Males should
avoid sperm donation;
9. Venous access can be established, peripheral blood mononuclear cells (PBMC) can be
collected in researcher's judgement;
10. The subject agrees to and sign informed consent form;
11. The subject can communicate well with the researcher, is willing and able to comply
with the research plans, and finish the research according to the research rule.
Exclusion Criteria:
1. Isolated extramedullary leukemia or isolated extramedullary disease relapse;
2. Central nervous system leukemia involved CNS3;
3. Concomitant malignancy other than cured non-melanoma skin cancer or cervical carcinoma
in situ or localized prostate cancer or superficial bladder cancer or ductal carcinoma
in situ or diagnosis of other malignancy exceeds 5 years without relapse or treatment
during the 5 years;
4. Any result of the following infectious disease tests is positive: HIV; HCV; HBsAg; or
HBcAb positive with HBV DNA copies positive; TPPA;
5. Live vaccine =4 weeks prior to enrollment;
6. For Ph+ ALL, TKI therapy =1 week prior to enrollment;
7. History of anti-CD19 therapy or CAR-T or other gene-editing T cell therapy;
8. Presence of = grade 2 acute graft-versus-host disease (GVHD, Glucksberg criteria) or
extensive chronic GVHD (Seattle criteria) that require treatment =4 weeks prior to
enrollment, or during the study period the subject is required to receive anti-GCHD
therapy in researcher's judgement;
9. Presence of concomitant disease that require systemic steroids or other immune
suppressive therapy during the study period in researcher's judgement; Allogeneic cell
therapy (such as donor lymphocyte infusion, DLI) =4 weeks prior to enrollment;
10. CNS stereotactic radiotherapy =4 weeks prior to enrollment;
11. Toxicities related to previous therapy did not relieved to =1 grade, except
hematological toxicity and alopecia;
12. Known life-threatening hypersensitivity to cyclophosphamide or fludarabine, or
presence of other intolerant conditions, or severe allergic constitution;
13. Patients with active autoimmune disease (e.g., systemic lupus erythematosus, sjogren
syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel
disease, Hashimoto's thyroiditis, hypothyroidism which can be controlled by thyroid
hormone replacement therapy is an exception);
14. For patients that underwent or plan to undergo major surgical operation before CAR-T
treatment, major surgery which required general anesthesia happened =4 weeks prior to
enrollment, or did not be fully recovered and clinically stable prior to enrollment,
or be anticipated to undergo major surgical operation which requires general
anesthesia during the study;
15. Took drug from other research=28 days prior to enrollment;
16. Any unstable cardiovascular diseases happened =6 months prior to enrollment, including
but not limited to, unstable angina, myocardial infarction, heart failure (NYHA grade=
III grade), severe arrhythmia that require drug interference, cardiac
angioplasty/coronary stent implantation/ cardiac bypass surgery =6 months prior to
enrollment;
17. Presence of central nervous system (CNS) disease or disease history, including
epilepsy, cerebral ischemia/bleeding, dementia, cerebellar disease, or any autoimmune
diseases that involve CNS;
18. Any other condition that researcher think it is inappropriate for the subject to
anticipate the trial.
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