clinical study of the safety and efficacy of bcma car-nk

Conditions: Immunotherapy; Multiple Myeloma

Summary: the goal of this clinical trial is to study of the safety and efficacy of chimeric antigen receptor nk cell injection targeting bcma (bcma car-nk) in patients with relapsed/refractory multiple myeloma primary endpoints: to evaluate the safety and tolerability of patients with relapsed/refractory multiple myeloma (rr/mm) after bcma car-nk infusion. to determine the maximum tolerated dose (mtd) and/or subsequent recommended dose (rd) of bcma car-nk in patients with rr/mm. secondary endpoints: to preliminarily evaluate the effectiveness of bcma car-nk in patients with rr/mm. to preliminarily evaluate the pharmacokinetic parameters of bcma car-nk cells in patients with rr/mm. to preliminarily evaluate bcma car-nk cell survival in subjects blood in relation to efficacy, adverse events and relevant biomarker levels. to preliminarily evaluate the relationship between donors and subjects kir-ligand mismatch and safety \& efficacy. to preliminarily evaluate the impact of the degree of hla genotype matching between donors and subjects on the survival of bcma car-nk cells in the subjects blood. subjects are enrolled and treated with lymphocyte clearance chemotherapy (including pre-clearance evaluation), pre-infusion evaluation and bcma car-nk cells infusion and enter the follow-up period after the end of the dlt observation period.


Eligibility criteria:
inclusion criteria: * age 18 years or above, no gender preference. * patients who have received at least 3 prior lines of treatment for multiple myeloma and have failed at least proteasome inhibitor and immunomodulator therapy; each line has at least 1 complete treatment cycle unless the best remission status for that treatment is documented as progressive disease (pd) (as per the imwg efficacy evaluation criteria published in 2016, appendix 4); pd must be documented during or within 12 months after receiving the last treatment. * presence of measurable lesions at screening, which are defined as any of the following situations: serum m protein≥1 g/dl (≥10 g/l) urinary m protein≥200 mg/24 hours serum free light chain (flc): abnormal serum flc ratio (\ 1.65) and involved flc≥10 mg/dl (100 mg/l) * ecog score (appendix 1): 0\~1. * expected survival≥3 months. * the following test values within 7 days prior to lymphocyte clearance meet the following criteria: hematology absolute lymphocyte count:≥0.5×109/l\[granulocyte colony-stimulating factor (g-csf) is allowed, but subjects should not have received this supportive therapy within 7 days prior to laboratory test during the screening period\] absolute neutrophil count:≥1.0×10\^9 /l\[granulocyte colony-stimulating factor (g-csf) is allowed, but subjects should not have received this supportive therapy within 7 days prior to laboratory test during the screening period\]. platelets:subjects platelet count ≥50 x 10\^9/l (subjects must not receive transfusion support within 7 days prior to laboratory test during the screening period) hemoglobin:≥8.0 g/dl (recombinant human erythropoietin is allowed) \[subjects have not received a red blood cell (rbc) transfusion within 7 days prior to laboratory test during the screening period\]. liver total bilirubin (serum) :total bilirubin (serum) ≤1.5 × uln ast and alt:≤3× uln * peripheral venous pathway meets the requirements of intravenous drip. * subjects agree to use reliable methods for contraception from the time of signing the informed consent till 1 year after the transfusion. * voluntary participation in the clinical trial and signing of the informed consent form. exclusion criteria: * subjects who have had a severe anaphylactic reaction. * subjects who received the following anti-mm therapy within a specific time prior to lymphocyte clearance. small molecule targeted therapy within 2 weeks or 5 half-lives (whichever is longer). large-molecule drug within 4 weeks or 2 half-lives (whichever is longer). cytotoxic drugs, modern chinese medicine preparations with antitumor effects within 2 weeks. immunomodulators therapy within 1 week. * subjects who have received a live or attenuated vaccine within 4 weeks prior to lymphocyte clearance. * subjects who have received the following therapy within 7 days prior to lymphocyte clearance, or that requires long-term treatment during the study period according to the investigators: systemic steroid therapy (except for inhaled one or topical use). immunosuppressive therapy. treatment of graft-versus-host response. * subjects presenting with incomplete recovery or stabilization to grade 1 (nci-ctcae v5.0) of toxicity (including peripheral neuropathy) caused by prior treatments. * cardiac disease: episode of myocardial infarction≤6 months prior to lymphocyte clearance; episode of unstable angina, severe arrhythmia as judged by the investigators, or coronary artery bypass graft≤3 months prior to lymphocyte clearance. * women who are pregnant or breastfeeding. * subjects who, in the opinion of the investigators, have any clinical or laboratory test abnormalities or other reasons that make them ineligible to participate in this clinical study.