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

Conditions: Multiple Myeloma in Relapse; Multiple Myeloma, Refractory

Summary: it is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-gprc5d car-t cells therapy for relapsed and refractory(r/r) multiple myeloma(mm).

this open label, single-arm, phase i study aims to evaluate the efficacy and safety of anti-gprc5d car-t in subjects with relapsed and refractory(r/r) multiple myeloma(mm). a leukapheresis procedure will be performed to manufacture anti-gprc5d chimeric antigen receptor (car) modified t cells. prior to anti-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. patients diagnosed with multiple myeloma according to international myeloma working group(imwg) diagnostic criteria; 4. subjects who had failed treatment with at least 3 drugs of different mechanisms (including chemotherapy, proteasome inhibitors, immunomodulators, etc.), or had progressed or relapsed during the last treatment period or within 6 months after the end of treatment; 5. the presence of measurable lesions at screening was determined according to any of the following criteria, defined as: (1) serum monoclonal immunoglobulin (m-protein) level ≥1.0 g/dl; (2) urine m protein level ≥200 mg/ 24h; (3) light chain multiple myeloma diagnosed with no measurable lesion in serum or urine: serum immunoglobulin free light chain ≥10 mg/dl and serum immunoglobulin κ/γ free light chain ratio abnormal; 6. 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); 7. eastern cooperative oncology group (ecog) score is 0-2; 8. survival is expected to be greater than 3 months; 9. adequate liver , kidney and cardiopulmonary function; 10. willingness to complete the informed consent process and to comply with study procedures and visit schedule. 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. clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis; 5. hbsag or hbcab are positive, and the quantitative detection of hepatitis b virus(hbv) dna in peripheral blood is more than 100 copies / l;hepatitis c virus (hcv) antibody and hcv rna in peripheral blood are positive; hiv antibody positive; syphilis antibody is positive in the first screening; 6. pregnant or breastfeeding; 7. 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;patients who received autologous hematopoietic stem cell transplantation (asct) within 8 weeks before screening, or who plan to undergo asct during the study period; 8. 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; 9. had hypersensitivity or intolerance to any drug used in this study; 10. persons with serious mental illness; 11. alcoholics or persons with a history of drug abuse; 12. systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment; 13. patients with acute/chronic graft-versus-host disease (gvhd) or requiring immunosuppressive therapy for gvhd within 6 months prior to screening; 14. any unsuitable to participate in this trial judged by the investigator.

Keywords: car-t gprc5d