nanobody-based biepitope car-t cells targeting bcma in the treatment of r/rmm

Conditions: Multiple Myeloma

Summary: to explore the safety and efficacy of nanobody-based bcma-targeting biepitope car-t cells in the treatment of relapsed/refractory multiple myeloma，this study will be conducted in multiple study centers, with 60 patients openly enrolled to receive car-t cell therapy. patients participating in clinical trials will be tested and evaluated for treatment safety, efficacy, duration of response, and long-term survival.

this study is a multicenter, open-label, prospective, single-arm clinical study with patients with relapsed/refractory multiple myeloma as the test subjects, in order to evaluate the safety and efficacy of nanobody-based biepitope car-t cells targeting bcma in the treatment of r/rmm, and to collect car-t pk/pd indicators. the structure of bcma target car-t is designed to identify two different epitopes of bcma protein with two recognition domains, in order to killig mm cells without secreting more pro-inflammatory factors and avoiding escape caused by the limitations of single bcma antigen recognition.

Eligibility criteria:
inclusion criteria: * patient or his or her legal guardian voluntarily participates in and signs an informed consent form. * aged ≥ 18 years and ≤ 75 years. * diagnosed as multiple myeloma (mm) according to the international standard for multiple myeloma (imwg 2014). * diagnosed as relapsed/refractory disease or primary refractory disease; relapse is defined as disease progression within 60 days of the most recent treatment with three or more lines of therapy with different mechanisms of action; refractory is defined as failure to achieve mr or above efficacy with prior treatment and disease progression with recent treatment, or disease progression within 60 days of treatment. * flow cytometry or immunohistochemistry showed positive bcma expression in myeloma cells. * have not been treated with antibody-based drugs within 2 weeks prior to cell therapy. * ecog score 0-2 points. * hgb≥70g/l，plt≥30×10\^9/l. * liver, kidney and cardiopulmonary functions meet the following requirements: 1. serum creatinine ≤ 1.5× uln or creatinine clearance (cockcroft-gault) \>30 ml/min； 2. left ventricular ejection fraction (lvef) ≥50%, 3. baseline peripheral oxygen saturation \> 90%; 4. total bilirubin ≤ 1.5×uln; alt and ast ≤2.5×uln. exclusion criteria: * previous diagnosis and treatment of other malignancies within 3 years; * presence of one of the following cardiac criteria: atrial fibrillation; myocardial infarction within the last 12 months; prolonged qt syndrome or secondary qt prolongation, as judged by the investigator. echocardiogram lvsf \<30% or lvef \<50%; clinically significant pericardial effusion; cardiac insufficiency nyha (new york heart association) iii or iv (absence of this symptom confirmed by echocardiography within 12 months of treatment); * patients with active gvhd; * patients with a history of severe pulmonary impairment disease; * combined with other malignant tumors in the advanced stage; * co-infection with severe or persistent infection that cannot be effectively controlled; * combined with severe autoimmune disease or congenital immunodeficiency; * active hepatitis (hepatitis b virus deoxyribonucleic acid \[hbv-dna ≥ 500 iu/ml and abnormal liver function\] or hepatitis c antibody \[hcv-ab\] positive, hcv-rna above the lower limit of detection of the analytical method and abnormal liver function); * human immunodeficiency virus (hiv) infection or syphilis infection; * patients with a history of severe allergy to biological products (including antibiotics); * patients with central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, etc; * pregnant or lactating women; patients and his or her spouses have a fertility plan within 12 months after car-t cell infusion; * other conditions considered inappropriate by the researcher.

Keywords: car-t bcma relapsed / refractory multiple myeloma