Safety, Tolerability, and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy for r/r B-ALL: a Clinical Trial

Inclusion criteria

• Patients will be enrolled only if they meet all the inclusion criteria.

• Patients with relapsed or refractory CD19+/CD22+ (FCM >95%) B-cell acute lymphoblastic leukaemia who have progressed despite or are intolerant to all standard therapies, including, but not limited to, immunotherapies such as Blinatumomab (BITE), Tyrosine kinase inhibitors (TKI), CAR T-cell therapy, etc.; Currently available therapies have a limited prognosis and there are no available curative treatment options (e.g., HSCT or chemotherapy);
• Peripheral blood tumour burden ≥60% or severe peripheral blood cytopenia, unsuitable/unable to collect autologous lymphocytes;
• 1 to 18 years old;
• Patient's expected survival time ≥ 60 days;
• Physical status: ECOG score 0-2;
• Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;
• Sign an informed consent form during the screening period. Pediatric patients under 8~18 years of age need to have sufficient awareness to voluntarily sign an informed consent form, and their legal representatives (guardians) also need to voluntarily sign an informed consent form; pediatric patients aged 1~7 years can only be recruited after their legal guardians have voluntarily signed an informed consent form.

Exclusion criteria

• Patients who meet any of the following criteria are not eligible for enrolment.

• Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);
• Intracranial hypertension or cerebral impaired consciousness;
• Symptomatic heart failure or severe cardiac arrhythmia;
• Symptoms of severe respiratory failure;
• With other types of malignant tumours;
• Diffuse intravascular coagulation;
• Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
• Suffering from sepsis or other uncontrollable infections;
• Suffering from uncontrollable diabetes mellitus;
• Severe mental disorders;
• Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);
• Have organ transplant history;
• Female patients (patients of childbearing potential) with positive blood HCG test;
• Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;
• No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.