BCMA and CD19 Targeted Fast Dual CAR-T for BCMA+ Refractory/Relapsed Multiple Myeloma

Inclusion Criteria:

1. Patients must have a confirmed prior diagnosis of active multiple myeloma as definedby the updated IMWG criteria;
2. Diagnosis of MM with relapsed or refractory disease. Definition of Refractory/relapse:
3. Have had at least 3 prior lines of therapy or primary refractory as defined byConsensus recommendations for the uniform reporting of clinical trials: report ofthe International Myeloma Workshop Consensus Panel 1. Prior therapy shouldinclude PI and IMiD. Note: Patients should undergone at least have at leastcomplete 1 cycle treatment in each line. Induction with or without hematopoieticstem cell transplant followed by maintenance therapy is considered a single lineof therapy.
4. Have had at least 2 prior lines of therapy when refractory to bothimmunomodulatory drug (IMiD) and proteasome inhibitor(PI) (Refractory was definedby IMWG consensus criteria);
5. Estimated life expectancy ≥3 months;
6. Hemoglobin ≥ 8.0 g/dL;
7. Absolute neutrophil count ≥ 0.75*10E9/L;
8. Platelet count ≥ 50*10E9/L;
9. Absolute lymphocyte count ≥ 1*10E8/L;
10. Liver, kidney and cardiopulmonary functions meet the following requirements: a)Totalbilirubin ≤ 2×ULN(except for Gilbert Syndrome); ALT and/or AST ≤3 × ULN; b)clearanceof serum creatinine ≥ 40 mL/min, calculated by Cockcroft-Gault; c)Corrected serumcalcium ≤ 12.5mg/dL or free ion calcium ≤ 6.5mg/dL(1.6mmol/L);
11. Sufficient venous access for leukapheresis collection, and no other contraindicationsto leukapheresis;
12. Subjects and sexual partner with fertility are willing to use effective and reliablemethod of contraception for at least 100 days after CART cell infusion;
13. Subjects must have signed written, informed consent.

Exclusion Criteria:

1. Accompanied by other uncontrolled malignancies.There are two exceptions to thiscriterion: Recepted radical therapy carcinoma without activity within 3 years beforescreening; and fully treated skin non-melanoma;
2. Any situations not benefit for subjects to accept or tolerated to planned therapy orunderstand informed consent; or any situation in which investigators believe thatparticipation in this study is not in the subject's best interests (e.g., harm tohealth), or any situation that may prevent, limit or confuse the assessment;
3. Convulsion or stoke within past 6 months;
4. Any instability of systemic disease within 6 months prior to screening, including butnot limited to congestive heart failure (New York heart association (NYHA)classification ≥ III), unstable angina, cerebrovascular accident, or transientcerebral ischemic, myocardial infarction,LEVF< 45% (assessed by an echocardiogram ormulti-door circuit scan );
5. Patients have central nervous system (CNS) metastases or CNS involvement (includingcranial neuropathies or mass lesions and leptomeningeal disease);
6. Subjects with positive HBsAg or HBcAb postive and peripheral blood HBV DNA titer ishigher than the lower limit of detection of the research institution; HCV antibodypositive; HIV antibody positive; syphilis primary screening antibody positive;
7. Presence or suspicion of fungi, bacteria, viruses or other infections that areuncontrollable or requiring intravenous treatment;
8. Activity of autoimmune diseases (such as crohn's disease, rheumatoid arthritis,systemic lupus erythematosus), orhistory of autoimmune disease within the last 3years;
9. Clinical evidence of dementia or changes of mental state.
10. Exist of pulmonary fibrosis;
11. Allergy subjects or history of severe hypersensitivity;
12. Oxygen inhalation requirment to maintain adequate oxygen saturation;
13. Surgery (except for local anesthesia surgery) plan 2 weeks before apheresis. during or 2 weeks after CART infusion;
14. Chemotherapy forbidden for cyclophosphamide or fludarabine;
15. Pregnant or lactating, or planning to have a pregnancy during or within 100 days aftertreatment;
16. Patients who are accounted to be not appropriate for this trail by investigator.