Clinical Study on the Safety and Efficacy of Autologous Hematopoietic Stem Cell Transplantation Combined With BCMA-CAR-T in the Treatment of Ultra-high Risk Multiple Myeloma
To evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (ASCT) combined with BCMA-CART in the treatment of UHR-MM.
⁃ Subjects must meet all of the following criteria to be enrolled:
⁃ Ultra high risk mm (UHR-MM), 18-70 years old, suitable for ASCT. And meet any of the following definitions of UHR-MM: 1) cytogenetic ultra-high risk, which meets any of the following conditions, including: del(17p)≥60%； Two or more cytogenetic features: TP53 mutation, del (17p) or p53 deletion, t (4; 14), t (14; 16), t (14; 20), 1q21 gain or amplification, 1p deletion, myc translocation (deletion or copy number abnormality: ≥ 20% is positive; translocation: ≥ 10% is positive); 2) Primary refractory (first-line induction therapy based on standard three drug combination: 2 courses \< Mr, 4 courses \< PR); 3) Early progression (the best first-line treatment response of the regimen based on the standard three drug combination is maintained for less than 6 months); 4) Plasma cell leukemia (meeting the diagnostic criteria of mm at the initial diagnosis, and the proportion of peripheral plasma cells ≥ 5%); 5) Non paraosseous extramedullary infiltration; 6) R2-iss-iv /mpss-iv.
• The subjects voluntarily participated in the study and signed the informed consent form (ICF) by themselves or their legal guardians;
• The subject must have proper organ function and meet all the following inspection results:
⁃ Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Creatinine clearance (CrCl) (Cockcroft Gault formula) ≥ 40ml/min; Prothrombin time (PT) ≤ 1.5 × ULN, partial prothrombin time (APTT) \< 1.5 × ULN, international normalized ratio (INR) \< 1.5 × ULN; Hemoglobin (HB) ≥ 60g/L; Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L (no growth factors such as granulocyte colony-stimulating factor \[G-CSF\] received within 7 days before laboratory examination in screening period); Absolute lymphocyte count (ALC) ≥ 0.5 × 10\^9/L; Platelet (PLT) ≥ 50 × 10\^9/L (no platelet transfusion within 7 days before laboratory examination in screening period); Left ventricular ejection fraction (LVEF) ≥ 45%; Blood oxygen saturation (SpO2) ≥ 92%; (3) The ECoG score is 0-1. See Appendix V for ECOG score; (4) Estimated survival ≥ 3 months; (5) The pregnancy test of fertile female subjects should be negative and not within the lactation period; Both female and male subjects need to take effective contraceptive tools or drugs within 24 months after cell infusion.
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