CD19/CD22 CAR-T Cell Therapy in MRD-Positive B-lineage Acute Lymphoblastic Leukemia in Children.

This clinical trial is a single-center, open-label, single-arm clinical trial to evaluate the safety and efficacy of CAR-T cell treatment for MRD-positive B-ALL. The specific trial process is divided as follows:

• Screen the enrolled population to determine the indications and exclusion criteria for cell treatment. In brief, intermediate-risk patients with positive MRD on day 46 of induction through flow cytometry according to CCCG-ALL regimen.
• Sign the informed consent form.
• CAR-T cell preparation: collect autologous lymphocytes and produce CAR-T cells targeting the CD19/CD22 target.
• Lymphocyte depletion pretreatment: according to the patient's condition, select the FC regimen (fludarabine 30 mg/m²/day for 4 days; cyclophosphamide 500 mg/m²/day for 2 days) before autologous transplantation.
• Cell intravenous infusion: dose: 3 × 10⁶/kg (allowable fluctuation range: 2 × 10⁶/kg - 4 × 10⁶/kg). Obeserve adverse reactions including CRS and ICANS.
• Evaluate the efficacy after the first cell infusion by MRD test .
• Continue chemotherapy after one month of CART according CCCG-ALL regimen from the second high-dose MTX of consolidation stage.
• Follow-up after the completion of the clinical study: within the first month after cell infusion, the subject needs to complete the relevant examinations required for follow-up on the 7th, 14th, 21st, and 30th days. Depending on the patient's condition, the number of detections may also be increased; from the 2nd to 6th months after infusion, follow-up once a month; from 6 months to 2 years after infusion, follow-up once every 3 months. From 2 to 5 years after infusion, follow-up once a year. After that, enter long-term follow-up.

Inclusion criteria

• Parents or legal guardians fully understand, are informed of this study and sign the informed consent form (ICF); are willing to follow and can complete all test procedures.
• Chinese children aged 1-18 years old at the time of screening, regardless of gender, with a body weight ≥ 10 kg.
• Bone marrow examination confirms that MRD is still positive on the 46th day after induction remission.
• Tumor cells in the bone marrow (BM) or peripheral blood (PB) express CD19/CD22 within 3 months before screening.
• Good organ function, which needs to meet the following criteria: (1)ALT ≤ 5 times the upper limit of normal value (ULN); (2)total bilirubin ≤ 2 times ULN (Gilbert's syndrome ≤ 3 times ULN); (3)without > grade 1 dyspnea when not inhaling oxygen, and oxygen saturation > 95%; (4)left ventricular ejection fraction (LVEF) ≥ 50%; (5)serum creatinine ≤ 1.5 times ULN.
• Karnofsky score (≥ 16 years old) ≥ 70 or Lansky (< 16 years old) score ≥ 50.
• Expected survival period of at least 12 weeks.
• Have sufficient venous access (for apheresis or venous blood sampling), and have no other contraindications for blood cell separation.

Exclusion criteria

• Have genetic diseases, except Down syndrome.
• Have a history of other malignancies or have other malignancies simultaneously.
• Meet any of the following conditions: (1)hepatitis B surface antigen (HBsAg) positive or HBV DNA quantification higher than the upper limit of normal value; (2)hepatitis C antibody (HCV Ab) positive and HCV RNA quantification higher than the upper limit of normal value; (3)human immunodeficiency virus antibody (HIV-Ab) positive; (4)Treponema pallidum antibody (TP-Ab) positive; (5)EBV DNA higher than the upper limit of normal value; (6)cytomegalovirus DNA higher than the upper limit of normal value.
• Have or are suspected to have uncontrolled or require intravenous drug treatment for fungal, bacterial, viral or other infections.
• Long-acting G-CSF is prohibited within 21 days before screening, and short-acting G-CSF is prohibited within 7 days before screening.
• Have active central nervous system leukemia.
• Are allergic to albumin and aminoglycoside antibiotics.
• Have undergone organ transplantation (except hematopoietic stem cell transplantation).
• Have participated in other interventional clinical studies within 3 months before screening (received active test drug treatment), or intend to participate in another clinical trial or receive anti-tumor treatment other than that specified in the protocol during the entire study period.
• Cannot tolerate chemotherapy and cytokine storm due to impaired function of important organs.
• Other situations that the investigator deems not suitable for participating in this clinical trial.