Dual-target CAR-T Cells (C-4-29) in the Treatment of Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

1. ≥18 years old, no gender limit;
2. Diagnosed with multiple myeloma according to the IMWG diagnostic criteria.
3. Received third-line and above regular treatments (including proteasome inhibitors orimmunomodulators) that are ineffective or intolerable;
4. The disease is measurable during screening:
5. Serum M protein level ≥0.5g/dL, or urine M protein level ≥200mg/24h;
6. Or light chain type MM with undetectable serum or urine disease: serumimmunoglobulin free light chain ≥10mg/dL and serum immunoglobulin κ/γ free lightchain ratio is abnormal;
7. Or evaluable extramedullary lesions with the largest transverse diameter ≥ 1 cm.
8. ECOG 0～2 points;
9. The expected survival time is more than 12 weeks;
10. No serious mental disorders;
11. The function of important organs is basically normal:
12. Heart function: echocardiography indicates that the cardiac ejection fraction is ≥50%, and the electrocardiogram has no obvious abnormalities;
13. Renal function: serum creatinine≤2.0×ULN;
14. Liver function: ALT and AST ≤3×ULN;
15. Total bilirubin and alkaline phosphatase≤2×ULN (Gilbert syndrome≤3.0×ULN);
16. Blood oxygen saturation>92%.
17. Have standards for apheresis or venous blood collection, and no other cell collectioncontraindications;
18. The subject agrees to use reliable and effective contraceptive methods forcontraception within 1 year after signing the informed consent form to receivingC-4-29 cell infusion (excluding safe period contraception).
19. The patient himself or his guardian agrees to participate in the clinical trial andsigns the ICF, indicating that he understands the purpose and procedures of theclinical trial and is willing to participate in the research.

Exclusion Criteria:

1. Have received CAR-T therapy or other genetically modified cell therapy;
2. With central nervous system disease at the time of screening ;
3. Participated in other clinical studies within 1 month before screening;
4. Have received a live attenuated vaccine within 4 weeks before screening;
5. Have received the following anti-tumor treatments before apheresis: receivedchemotherapy, targeted therapy or other experimental drug treatments within 14 days orat least 5 half-lives (whichever is shorter);
6. Within 7 days before apheresis, there are active infections or uncontrollableinfections that require systemic treatment (except CTCAE grade 1 genitourinary systeminfection and upper respiratory tract infection);
7. Suffered from plasma cell leukemia at the time of screening ;
8. Suffered from other malignant tumors other than multiple myeloma within 3 years beforescreening, except for the following cases: malignant tumors that have received radicaltreatment, and there is no known active disease for ≥3 years before enrollment; orfully treated non-melanoma skin cancer with no evidence of disease;
9. Except for hair loss or peripheral neuropathy, the toxicity of previous anti-tumortreatments has not improved to the baseline level or ≤grade 1;
10. Subjects who have received systemic steroid treatment within 7 days before apheresisor who have been determined by the investigator to require long-term systemic steroidtreatment during treatment (except for inhaled or topical use);
11. Suffered from any of the following heart diseases:
12. NYHA stage III or IV congestive heart failure;
13. Myocardial infarction or CABG occurred ≤6 months before enrollment;
14. Clinically significant ventricular arrhythmia, or history of unexplained syncope (except for cases caused by vasovagal or dehydration);
15. History of severe non-ischemic cardiomyopathy.
16. Active autoimmune diseases;
17. HBsAg or HBcAb positive and HBV DNA is greater than the normal range; HCV antibody ispositive and HCV RNA greater than the normal range; HIV antibody positive; syphilispositive; CMV DNA positive;
18. Have experienced a venous embolism event (for example: pulmonary embolism or deep veinthrombosis) and requires anticoagulation therapy or the subject meets the followingconditions: a. Bleeding of grade 3 to 4 lasting more than 30 days; b. Have sequelaecaused by venous thrombosis (such as persistent dyspnea and hypoxia);
19. Women who are pregnant or breastfeeding, and male or female subjects who plan to havechildren within 1 year after receiving C-4-29 cell reinfusion;
20. Other situations considered by the researcher to be unsuitable to participate in thestudy.