a study of car-t cells targeting gprc5d in the treatment of r/r multiple myeloma

Conditions: Multiple Myeloma

Summary: this is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability, cellular kinetics and initial efficacy of car-t cell therapy targeting gprc5d in multiple myeloma subjects who have failed the standard treatments.


Eligibility criteria:
inclusion criteria: 1. the subject can understand and have the ability to sign an informed consent form; 2. male or female subjects, aged 18-75 years; 3. the expected survival period is not less than 12 weeks; 4. ecog score ≤ 2 ; 5. diagnosed as multiple myeloma according to the imwg standard in 2018; 6. the expression of gprc5d in bone marrow plasma cells is more than 20%, or it is positive in tumor tissue by immunohistochemistry. one of the following criteria must be detected: 1. if igg type mm, serum m protein ≥10g/l; if iga, igd, ige or igm type mm, serum m protein ≥5g/l; 2. or urine m protein level ≥200mg/24h; 3. or light chain type mm, serum free light chain (sflc) ≥ 100mg / l and k/ λ flc ratio is abnormal; 4. or there are extramedullary lesions; 7. subjects who have received at least 3 different mechanism drugs (including chemotherapy, protease inhibitors, immunosuppressive agents, etc.) have failed treatments, or have progressed or recurred during the last treatment or within 6 months after the end of treatment ; 8. lung function is normal, and oxygen saturation is greater than 92%; 9. no heart disease or coronary heart disease, echocardiogram showed normal diastolic function, left ventricular ejection fraction (lvef) ≥50%, and no serious arrhythmia; 10. liver function: tbil\<3×uln, ast\<2.5×uln, alt\<2.5uln; 11. renal function: creatinine clearance rate (estimated by cockcroft gault formula) ≥ 30 ml/min; 12. the blood routine meets the following standards: 1. lymphocyte count\>0.5×10e9/l; 2. neutrophils ≥1.0×10e9/l; 3. hemoglobin ≥80g/l; 4. platelet ≥75×10e9/l 13. from the use of study drug to 2 years after treatment, male subjects or female subjects of childbearing age must agree and be able to take effective contraceptive measures. exclusion criteria: 1. pregnant or breastfeeding; 2. hbsag or hbcab are positive, and the quantitative detection of hbv dna in peripheral blood is more than 100 copies / l; hcv antibody and hcv rna in peripheral blood are positive; hiv antibody positive; syphilis antibody is positive in the first screening; 3. any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (new york heart association \[nyha\] classification ≥ grade iii), severe arrhythmia with poor drug control, liver, kidney or metabolic diseases; 4. had hypersensitivity or intolerance to any drug used in this study; 5. patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening; 6. uncontrolled malignant tumors except mm, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment; 7. clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis; 8. in the past two years, autoimmune diseases (such as crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs, or required systemic application of immunosuppressive or other drugs; 9. severe active viral, bacterial or uncontrolled systemic fungal infections; hereditary bleeding / coagulation diseases, history of non traumatic bleeding or thromboembolism, other diseases that may increase the risk of bleeding, etc; 10. patients who received autologous hematopoietic stem cell transplantation (asct) within 8 weeks before screening, or who plan to undergo asct during the study period; 11. patients received allogeneic stem cell therapy; 12. any unsuitable to participate in this trial judged by the investigator.

Keywords: car-t gprc5d multiple myeloma