RRMM
Conditions
Interventions
Group:The dosing frequency was once every 3 days, for a total of 3 times: the dose for group A was 0.03 mg/kg
Group B:The dosing frequency was once every 3 days, for a total of 3 times: the dose for group A was 0.06 mg/kg
Group C:The dosing frequency was once every 3 days, for a total of 3 times: the dose for group A was 0.12 mg/kg
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age >=18 and =10 g/L or urine M-protein level >=200 mg/24 hours. · IgA, IgD, IgM, or IgE myeloma: serum M-protein level >=5 g/L or urine M-protein level >=200 mg/24 hours. · Light chain myeloma with no measurable disease in serum or urine: serum free light chain >=100 mg/L and an abnormal serum free light chain ratio. 4. Relapsed/refractory multiple myeloma: previously treated with at least 3 prior therapeutic agents (including immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies), and/or determined by the investigator to have progressed after receiving adequate standard treatment regimens based on comprehensive assessment of the participant's condition. Prior exposure may come from different single-agent or combination therapy regimens. 5. ECOG performance status 0-1. 6. Bone marrow function test results (at screening or within 2 months prior to screening) meeting the following criteria: · Hemoglobin >=60 g/L (without red blood cell transfusion within 1 week prior to screening); recombinant human erythropoietin is permitted. · Absolute neutrophil count (ANC) >=500/µL (without granulocyte colony-stimulating factor (G-CSF) within 1 week prior to screening, or without pegylated G-CSF within 2 weeks prior to screening). · Platelet count >=50,000/µL. · Lymphocyte count >=500/µL. · Absolute CD3-positive T cell count >=150/µL. 7. Adequate organ function at screening, meeting the following criteria: · AST =60 mL/min (Cockcroft and Gault formula). · Minimum level of pulmonary reserve, defined as dyspnea 90% while breathing ambient air. · INR =40% (measured by echocardiography or MUGA scan). · No clinically significant pericardial effusion detected. · No clinically significant electrocardiogram (ECG) abnormalities detected. 9. Female patients of childbearing potential must have a negative pregnancy test. Both male and female patients must agree to use effective contraception during treatment and for 1 year thereafter. 10. Expected survival >3 months. 11. Voluntary signed informed consent.
Exclusion criteria
Exclusion criteria: 1. Non-active multiple myeloma, MGUS (monoclonal gammopathy of undetermined significance), or smoldering myeloma. 2. Current or prior diagnosis of the following diseases: primary amyloidosis, Waldenström's macroglobulinemia, POEMS syndrome, or plasma cell leukemia at screening, defined as plasma cells > 2.0 × 10?/L. 3. Received other anti-cancer therapy during the screening period (as determined primarily by the investigator): · Received targeted therapy, epigenetic therapy, other investigational drug therapy, or treatment involving invasive investigational medical devices within 5 half-lives. · Received immune/non-immune-directed systemic therapy within 1 week. · Received cytotoxic therapy within 1 week. · Received proteasome inhibitors and immunomodulatory agents within 2 weeks. · Received radiotherapy within 4 weeks (except that subjects are eligible regardless of the radiotherapy end date if the radiation field covered =5% of bone marrow reserve). 4. Primary refractory multiple myeloma: disease progression during first-line therapy without achieving at least minimal response (MR) or better. 5. Clinically symptomatic central nervous system involvement. 6. History of other malignancies other than multiple myeloma within 3 years prior to screening (excluding malignancies that have been cured and have a very low risk of recurrence within 3 years). 7. Voluntary withdrawal of informed consent by the patient. 8. The investigator determines that study withdrawal is in the patient's best interest, or in the investigator's opinion, the patient's medical history, psychiatric history, or laboratory abnormalities may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of results. 9. Patients who are positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with detectable peripheral blood hepatitis B virus (HBV) DNA titer above the normal range within 6 months prior to infusion; positive for hepatitis C virus (HCV) antibody with detectable peripheral blood HCV RNA titer above the normal range; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis test. 10. Any other uncontrolled active disease that precludes participation in the trial. 11. History of, or strong suspicion of, interstitial lung disease; or presence of pulmonary abnormalities that may interfere with the detection or management of suspected drug-related pulmonary toxicity during the trial. 12. History of poorly controlled psychiatric disorders. 13. Patients deemed unsuitable for participation in the trial by the investigator. 14. Long-term use of immunosuppressants (e.g., post-organ transplantation), except for inhaled corticosteroid therapy. 15. Known severe hypersensitivity to tLNP-mRNA or any of its formulation components. 16. Known severe hypersensitivity to tocilizumab. 17. Patients in whom a suitable intravenous access cannot be established. 18. Unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events within 30 days prior to enrollment. If receiving anticoagulation therapy, the subject's therapeutic dose must be stable prior to enrollment. 19. Pregnant or breastfeeding subjects, or subjects planning to become pregnant during the treatment period or within 1 year after treatment completion; female subjects of childbearing potential who are unwilling to use highly eff
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerability; | — |
Secondary
| Measure | Time frame |
|---|---|
| Stringent Complete Response (sCR)Complete Response (CR)Very Good Partial Response (VGPR)Partial Response (PR)Minor Response (MR)Stable Disease (SD) Overall Response Rate (ORR)Duration of Response (DOR)Time to Response (TTR) Progression-Free Survival (PFS)Minimal Residual Disease (MRD)Overall Survival (OS)Quality of Life (QoL) (based on EORTC QLQ-C30)Safety; | — |
Countries
China
Contacts
Public ContactTing Niu
Department of Hematology, West China Hospital of Sichuan University
Outcome results
None listed