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 finishall 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 linestreatment (must including the proteasome inhibitors and immune modulators); Refractorymultiple 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 subsequenttreatment process or disease progress within 60 days after the last treatment ;
6. Have a measurable lesions in screening period (conform to one of the followingstandards: (1) the serum M protein: IgG protein≥10g/L, or IgA M protein ≥5g/L, or IgDM protein ≥5g/L; (2) M protein urine ≥200mg/24h; (3)If M protein in serum or urinecannot be measured,under the condition of the abnormal serum free light chainratio,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 withoutblood transfusion),PLT≥ 50 x 10 ^ 9 / L(7 days before the inspection without bloodtransfusion) ,ALC≥0.3×10^9/L,ANC≥0.75×10^9/L; (2)AST≤3ULN,ALT≤3ULN,TBIL≤2ULN；Ccr≥30mL/min/1.73 m2;Correction of serum calcium ≤3.1mmol/L（≤12.5mg/dL）; LVEF≥40%； Baselineperipheral blood oxygen saturation ≥95%;
8. Female subjects with fertility ,pregnancy blood test results should be negative inscreening 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 researchcenter; Hepatitis c virus (HCV) antibody positive and peripheral blood HCV - RNApositive subjects; Antibodies to HIV positive subjects; Early syphilis screeningantibody positive;
2. The other clinical significance of active virus, bacterial infection, or failing tocontrol 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 ofserious arrhythmia, liver, kidney or metabolic diseases, as well as the standardtreatment cannot control high blood pressure;
4. In past two years, because of autoimmune diseases such as crohn's disease, rheumatoidarthritis and systemic lupus erythematosus (sle), etc.) causing end-organ damage, orneed systemic application of immunosuppressive drugs;
5. Had a history of the central nervous system diseases, such as epilepsy, serious braindamage, dementia, Parkinson's disease, psychosis,etc which influence the appraising oftest,;
6. Diagnosed with other active malignancy in past five years(the basal or scaly skincancer, superficial bladder cancer, breast cancer in situ, which has been cured anddoes not require follow-up treatment are not included );
7. Known allergic to cyclophosphamide, fluorine dara marina or CAR - T cell s includingaccessories, DMSO ;
8. Patients with pregnancy or lactation, patients do not want to take effectivecontraceptive measures within 6months after infusion CAR-T cells;
9. The other situations that researchers determined doesn't fit to participate in thisstudy.