A Dose Escalating Study of CD19/CD22/BCMA Three Targets Autologous Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Subjects With Relapsed/Refractory Multiple Myeloma
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologouschimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed/refractory multiple myeloma.
• Participants must meet all of the following criteria in order to be enrolled:
‣ Understand and voluntarily sign an informed consent form (ICF) before conducting any research related evaluations/procedures;
⁃ Age range: 18-75 years old;
⁃ Expected survival period is not less than 12 weeks;
⁃ ECOG score ≤ 2 points;
⁃ The bone marrow flow cytometry results showed positive BCMA antigen (including weak positive, moderate positive, and strong positive);
⁃ According to the IMWG criteria, a diagnosis of multiple myeloma with measurable lesions must meet at least one of the following criteria:
• Serum M protein (SPEP) ≥ 5g/L
∙ 24-hour urinary M-protein excretion rate ≥ 0.2g (200mg)
∙ Serum free light chain (sFLC) ≥ 100 mg/L and abnormal free light chain ratio
∙ The ratio of primitive plasma cells to immature plasma cells in bone marrow cytology examination is greater than 5%, or the flow cytometry detection of monoclonal plasma cells is greater than 5%
⁃ Those who have received treatment with at least three different mechanisms of action (including anti-CD38 monoclonal antibodies, protease inhibitors, immunosuppressants, etc.) but have failed, and have experienced relapse (within 12 months), difficulty in treatment, or intolerance to the last line treatment regimen, including primary difficulty in treatment (subjects who have not achieved minimal remission \[MR\] or developed disease progression \[PD\] during treatment) or secondary difficulty in treatment (subjects who develop disease progression within 60 days after completion of treatment);
⁃ There is no significant abnormality in lung function, and the oxygen saturation is greater than 92% in the absence of oxygen inhalation;
⁃ The blood biochemistry test results meet the following criteria:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
∙ Total bilirubin ≤ 1.5 × ULN
∙ 24-hour serum creatinine clearance rate ≥ 30 mL/min
∙ Lipase and amylase ≤ 2 × ULN
‣ The blood routine test meets the following criteria:
⁃ Lymphocyte count\>0.5 × 10 \^ 9/L
• Neutrophil count ≥ 1.0 × 10 \^ 9/L
• Hemoglobin ≥ 60g/L
• Platelets ≥ 40 × 10 \^ 9/L
‣ Men with fertility and women of childbearing age must agree to use effective contraceptive measures from the signing of the informed consent form until 2 years after the use of the study drug. Women of childbearing age include premenopausal women and women within 2 years after menopause. The blood pregnancy test for women of childbearing age must be negative during screening.