Targeting CD19 and BCMA CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Multiple Myeloma

Inclusion Criteria: 1. Agreed to participate in this study and signed informed consent, and willing to finish all the test procedure. 2. Age ≧ 18 years of age, gender not limited; 3. According to IMWG， diagnosis of multiple myeloma patients; 4. ECOG physical score ≤2 points ; 5. Relapsed multiple myeloma: disease progressed after received at least 3 lines treatment (must including the proteasome inhibitors and immune modulators); Refractory multiple myeloma: early treatment has never reached more than MR and curative effect; Or early treatment has reached more than MR and curative effect, but the subsequent treatment process or disease progress within 60 days after the last treatment ; 6. Have a measurable lesions in screening period (conform to one of the following standards: (1) the serum M protein: IgG protein≥10g/L, or IgA M protein ≥5g/L, or IgD M protein ≥5g/L; (2) M protein urine ≥200mg/24h; (3)If M protein in serum or urine cannot be measured,under the condition of the abnormal serum free light chain ratio,serum free light chain immunoglobulin or 100 mg/L; 7. Test results in screening period: (1) Hb≥60 g/L (7 days before the inspection without blood transfusion),PLT≥ 50 x 10 \^ 9 / L(7 days before the inspection without blood transfusion) ,ALC≥0.3×10\^9/L,ANC≥0.75×10\^9/L; (2)AST≤3ULN,ALT≤3ULN,TBIL≤2ULN；Ccr≥30 mL/min/1.73 m2;Correction of serum calcium ≤3.1mmol/L（≤12.5mg/dL）; LVEF≥40%； Baseline peripheral blood oxygen saturation ≥95%; 8. Female subjects with fertility ,pregnancy blood test results should be negative in screening period and before remove the lymphocyte ; 9. Expected to survival more than 3 months; Exclusion Criteria: 1. The active hepatitis b, HBV - DNA detection lower limit of the subjects above research center; Hepatitis c virus (HCV) antibody positive and peripheral blood HCV - RNA positive subjects; Antibodies to HIV positive subjects; Early syphilis screening antibody positive; 2. The other clinical significance of active virus, bacterial infection, or failing to control systemic fungal infection; 3. Any instability of systemic disease, including but not limited to, unstable angina, cerebrovascular accident, or transient ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York heart association (NYHA) classification level III or higher congestive heart failure, drug control of serious arrhythmia, liver, kidney or metabolic diseases, as well as the standard treatment cannot control high blood pressure; 4. In past two years, because of autoimmune diseases such as crohn's disease, rheumatoid arthritis and systemic lupus erythematosus (sle), etc.) causing end-organ damage, or need systemic application of immunosuppressive drugs; 5. Had a history of the central nervous system diseases, such as epilepsy, serious brain damage, dementia, Parkinson's disease, psychosis,etc which influence the appraising of test,; 6. Diagnosed with other active malignancy in past five years(the basal or scaly skin cancer, superficial bladder cancer, breast cancer in situ, which has been cured and does not require follow-up treatment are not included ); 7. Known allergic to cyclophosphamide, fluorine dara marina or CAR - T cell s including accessories, DMSO ; 8. Patients with pregnancy or lactation, patients do not want to take effective contraceptive measures within 6months after infusion CAR-T cells; 9. The other situations that researchers determined doesn't fit to participate in this study.