safety and efficacy of anti-bcma-gprc5d car-t cells therapy in the treatment of r/r mm

Conditions: Relapsed/Refractory Multiple Myeloma

Summary: this is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific bcma-gprc5d car-t cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.

this is a single-center, open-label, single-arm study to evaluate the safety and efficacy of bispecific bcma-gprc5d car-t cells in patients with relapsed or refractory multiple myeloma who received three or more lines of therapy.a leukapheresis procedure will be performed to manufacture anti-bcma-gprc5d chimeric antigen receptor (car) modified t cells. prior to anti-bcma-gprc5d car-t cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. after infusion, the safety and efficacy of car-t therapy was evaluated by investigators.

Eligibility criteria:
inclusion criteria: 1. the patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure; 2. age 18-75 years old, gender unlimited; 3. diagnosed as multiple myeloma (mm) according to the international standard for multiple myeloma (imwg); 4. the presence of measurable disease at screening meets one of the following criteria:serum m-protein ≥ 1.0 g/dl or urine m-protein ≥ 200 mg/24h or diagnosed as light-chain mm without measurable disease in serum and urine; serum free light chain ≥ 10 mg/dl with an abnormal κ/λ ratio; 5. patients must relapse or be refractory after three or more lines of therapy, which at least include: one proteasome inhibitor (pi), one immunomodulatory drug (imid), and one anti-cd38 monoclonal antibody; 6. diagnosed as relapsed/refractory disease or primary refractory disease; 7. the last treatment is ineffective, or the disease progresses within 60 days after the end of the last therapy; 8. the patient has recovered from the toxicity of the prior treatment, i.e., ctcae toxicity grade \< 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy); 9. ecog score 1-2 points and the expected survival period ≥ 3 months; 10. liver, kidney and cardiopulmonary functions meet the following requirements: 1. total bilirubin ≤ 1.5×uln, alanine aminotransferase (alt) ≤ 3 × uln and aspartate aminotransferase (ast) ≤ 3 × uln; 2. serum creatinine ≤ 1.5×uln, or creatinine clearance ≥ 60 ml/min; 3. hemoglobin (hb) ≥ 50 g/l without prior blood transfusion within 7 days; 4. baseline peripheral oxygen saturation \> 92%; 5. corrected serum calcium ≤ 12.5 mg/dl (≤ 3.1 mmol/l) or free (ionized, ionic) calcium ≤ 6.5 mg/dl (≤ 1.6 mmol/l); 6. left ventricular ejection fraction (lvef) \> 45%, without confirmed pericardiac effusion and abnormal electrocardiography with clinical significance; 7. without clinically significant pleural effusion; 11. venous access could be established; without contraindications of apheresis. exclusion criteria: 1. have been diagnosed with or treated for aggressive malignancies other than multiple myeloma; 2. prior antitumor therapy (prior to blood collection for car-t preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter; 3. it is suspected that mm has involved the central nervous system or meninges and has been confirmed by mri or ct, or there are other active central nervous system diseases; 4. patients with fahrenheit macroglobulinemia, poems syndrome, or primary al, amyloidosis; 5. subjects with positive hbsag or hbcab positive and peripheral blood hbv dna titer is higher than the lower limit of detection of the research institution; hcv antibody positive; hiv antibody positive; cmv dna titer is higher than the lower limit of detection of the research institution; ebv dna titer is higher than the lower limit of detection of the research institution; 6. patients have a severe allergic history; 7. 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 \[new york heart association (nyha) classification ≥ grade iii\]; 8. systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment; 9. patients with acute/chronic graft-versus-host disease (gvhd) or requiring immunosuppressive therapy for gvhd within 6 months prior to screening; 10. active autoimmune or inflammatory diseases of the nervous system; 11. patients develop oncology emergencies and need to be treated before screening or infusion; 12. uncontrolled infections that need antibiotics treatment; 13. exposure to hematopoietic growth factor of cells within 1-2 weeks before apheresis; 14. exposure to corticosteriods or immunosuppressive agents within 2 weeks before apheresis; 15. patients receive a major surgical operation within 4 weeks before lymphodepletion or do not recover completely before the enrollment; or plan to receive a major surgical operation during the study period; 16. live attenuated vaccine within 4 weeks before screening; 17. persons with serious mental illness; 18. alcoholics or persons with a history of drug abuse; 19. pregnant or lactating women; patients and his or her spouse have a fertility plan within two years after car-t cell infusion; 20. any unsuitable to participate in this trial judged by the investigator.

Keywords: bcma-gprc5d car-t