| Eligibility |
Inclusion Criteria:
1. Informed consent is signed by a subject or his lineal relation.
2. Age 3 and older.
3. Documentation of cluster of differentiation 19 (CD19) and or cluster of
differentiation 19 (CD22) expression on leukemic blasts in the BM, peripheral blood
within 3 months of screening.;
4. Relapsed or refractory B-cell ALL
- Relapse within 12 months of first remission
- Without remission after 2 cycles of induction chemotherapy regimen.
- Without remission or relapse after salvage treatments.
- Any BM relapse after autologous stem cell transplantation (ASCT).
5. Without remission or relapse after any prior CD19 targeted therapy;
6. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are
intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI); no
TKI salvage treatments if the patient has a BCR-ABL1 kinase domain gatekeeper mutation
Thr315Ile (T315I) mutation.
7. Bone marrow with = 5% lymphoblasts by morphologic assessment at screening;
8. Eastern cooperative oncology group (ECOG) performance status of 0 to 2.
9. Adequate organ function defined as:
- Aspartate aminotransferase (AST) =3 upper limit of normal (ULN);
- Serum alanine aminotransferase (ALT) =3 ULN;
- Total bilirubin = 2 ULN, except in individuals with Gilbert's syndrome;
- Note: Patients with Gilbert's syndrome that bilirubin = 3 ULN and direct
bilirubin = 1.5 ULN will be eligible.
- A serum creatinine= 1.5 ULN or Creatine removal rate = 60mL/min(Cockcroft and
Gault)
- Must have a minimum level of pulmonary reserve as = Grade 1 dyspnea and oxygen
saturation > 91% on room air.
- Absolute lymphocyte count =0.3 x 10?/L.
10. Women of child-bearing potential and all male participants must use highly effective
methods of contraception for a period of 1 year after the CD19-CD22 CAR-T cells
infusion.
Exclusion Criteria:
1. Active central nervous system leukemia
2. Patients with evidence of currently uncontrollable serious active infections (e.g.,
sepsis, bacteremia, fungemia, viremia, etc.).
3. Patients who are positive for any of HIV antibody, TP antibody, hepatitis B surface
antigen (HBsAg) and hepatitis C virus (HCV) antibody.
4. Major surgery within = 4 weeks before enrollment.
5. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
intent.
6. Impaired cardiac function:
- Left Ventricular Ejection Fraction (LVEF) =45%;
- III/IV congestive heart failure (NYHA);
- Severe arrhythmia (except for Atrial fibrillation, Paroxysmal supraventricular
tachycardia);
- Corrected QT interval (QTc) =450ms (male) or QTc=470ms (female)(QTc using
Bazett's formula (QTcB)=QT/RR^0.5);
- Myocardial infarction or Coronary Artery Bypass Graft Surgery, heart stent
surgery.
- Other heart diseases that have been judged by the investigator to be unsuitable
for receiving cell therapy.
7. Patients with a history of epilepsy or other active central nervous system diseases.
8. Life expectancy < 12 weeks.
9. Allergy to macromolecule biopharmaceuticals such as antibodies or cytokines.
10. Subjects who are receiving systemic steroid treatment and who have been determined by
the researchers to require long-term treatment with systemic steroids during
treatment, and subjects treated with systemic steroids must be excluded < 72 hours
prior to CNCT19 infusion (except inhalation or local use).
11. Patients with other conditions making the patients unsuitable for receiving cell
therapy as judged by the investigator.
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