recurrent/refractory multiple myeloma
Conditions
Interventions
Low dose group:Venous reinfusion of of 1×10^6/kg CAR+ cells
Medium dose group:Venous reinfusion of of 3×10^6/kg CAR+ cells
High dose group:Venous reinfusion of of 6×10^6/kg CAR+ cells
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology/West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged 18 years and over, male or female; 2. Subjects diagnosed with multiple myeloma according to IMWG diagnostic criteria (Appendix 2) and meeting one of the following conditions: (1) Recurrence after previous complete remission (CR): M protein reappears in serum or urine, or plasma cells in bone marrow exceed 5%, or new mm symptoms (osteolytic damage, plasma cell tumor, hypercalcemia or anemia, etc.); (2) Failure to reach Cr in the past: at least one of serum M protein, 24h urinary light chain or bone marrow plasma cells increased by more than 25%, and the new or original symptoms of mm were further aggravated; (3) No response to the existing treatment or disease progression within 60 days after the end of the previous treatment, which was confirmed by the investigator (judged according to the IMWG standard). 3. Ineffective or intolerable third-line or above regular treatment (including proteasome inhibitors or immunomodulators); 4. The disease can be measured during screening, that is, it meets one of the following conditions: (1) Serum M protein level >= 0.5g/dl, or urinary M protein level >= 200mg / 24h; (2) Or light chain mm with undetectable serum or urine diseases: serum immunoglobulin free light chain >= 10mg / dl and serum immunoglobulin ?/? Abnormal free light chain ratio; (3) There were evaluable extramedullary lesions with a maximum transverse diameter >= 1cm. 5. ECOG 0 - 2 points (Appendix 3); 6. The expected survival time is more than 12 weeks; 7. No serious mental disorders; 8. The functions of important organs are basically normal: (1) Cardiac function: cardiac ultrasound showed that the cardiac ejection fraction was >= 50%, and there was no obvious abnormality in ECG; (2) Renal function: serum creatinine 92%. 9. It has the standard of single blood collection or venous blood collection, and there are no contraindications to other cell collection; 10. The subjects agreed to use reliable and effective contraceptive methods for contraception (excluding safe period contraception) within 1 year after signing the informed consent form and receiving c-4-29 cell infusion. Including but not limited to: abstinence, implantable progesterone contraceptives that can inhibit ovulation; Intrauterine device (IUD); Intrauterine hormone release system; Spouse vasectomy; Compound hormonal contraceptives that can inhibit ovulation (oral, vaginal and percutaneous administration); Progesterone contraceptives that inhibit ovulation (oral or injection); When male subjects have sexual life with fertile women, they must agree to use barrier contraception (such as condoms, killer foam / gel / film / emulsion / suppository). At the same time, the subjects should promise not to donate eggs (eggs, oocytes) or sperm for assisted reproduction within 1 year after cell infusion; 11. The patient or his guardian agrees to participate in the clinical trial and sign the ICF, indicating that he understands the purpose and procedure of the clinical trial and is willing to participate in the study.
Exclusion criteria
Exclusion criteria: 1. Patients receiving BCMA targeted drug therapy, CAR-T therapy or other gene modified cell therapy; 2. Central nervous system involvement in multiple myeloma during screening; 3. Participation in other clinical trial within 1 month before screening; 4. Live attenuated vaccine being inoculated within 4 weeks before screening; 5. Reciving the following antitumor treatment before apheresis: received chemotherapy, targeted therapy or other experimental drug treatment within 14 days or at least 5 half-life (whichever is shorter); 6. Active infection or uncontrollable infection requiring systemic treatment (except ctcae1 urogenital system infection and upper respiratory tract infection) existed within 7 days before apheresis; 7. Plasma cell leukemia at screening (plasma cells > 2.0 x 10^9/L according to standard classification); 8. Other malignant tumors other than multiple myeloma within 3 years before screening, except for the following cases: malignant tumors that have received radical treatment and have no known active diseases within >= 3 years before enrollment; Or fully treated non melanoma skin cancer with no evidence of disease; 9. Except for alopecia or peripheral neuropathy, the toxicity of previous antitumor treatment did not improve to the baseline level or <= grade 1; 10. Subjects who received systemic steroid treatment within 7 days before apheresis or who were determined by the investigator to need long-term systemic steroid treatment during treatment (except inhalation or local use); 11. Any of the following heart diseases: (1) New York Heart Association (NYHA) stage III or IV congestive heart failure; (2) Myocardial infarction or coronary artery bypass grafting (CABG) occurred <= 6 months before enrollment; (3) A history of clinically significant ventricular arrhythmia or unexplained syncope (except due to vasovagal or dehydration); (4) History of severe non ischemic cardiomyopathy. 12. Active autoimmune diseases; 13. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is larger than the normal range. Hepatitis C virus (HCV) antibody was positive and the titer of HCV RNA in peripheral blood was greater than the normal range; Human immunodeficiency virus (HIV) antibody positive; Syphilis test positive; Cytomegalovirus (CMV) DNA positive; 14. Subject had venous embolism (e.g. pulmonary embolism or deep venous thrombosis) and needed anticoagulant treatment, or the subject met the following conditions: (1) Grade III to IV bleeding lasted for more than 30 days; (2) Sequelae caused by venous embolism (such as persistent dyspnea and hypoxia); (Note: subjects who have venous embolism but do not meet the above conditions can participate in the test); 15. Women in pregnancy or lactation, and male or female subjects with family planning within 1 year after receiving C-4-29 cell reinfusion; 16. Other researchers believe that it is not suitable to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Dose-limiting toxicity, DLT;adverse event;ECOG score; | — |
Secondary
| Measure | Time frame |
|---|---|
| immunogenicity;Cell kinetic parameters; | — |
Countries
China
Contacts
Public ContactLiu Ting
West China Hospital, Sichuan University
Outcome results
None listed