Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease
Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Prospective, Single-Arm, Multicenter, Open-Label Study
Institute of Hematology & Blood Diseases Hospital, China
20 participants
Apr 9, 2025
INTERVENTIONAL
Conditions
Summary
This is a prospective, single-arm, multicenter, open-label study to evaluate the efficacy and safety of aponermin-based bridging therapy prior to CAR-T infusion in relapsed/refractory multiple myeloma patients with extramedullary disease.
Eligibility
Inclusion Criteria15
- Be informed and voluntarily sign the Informed Consent Form (ICF).
- Age ≥18 years.
- Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines)
- Subjects with diagnosed relapsed or refractory extramedullary multiple myeloma according to IMWG criteria and have had at least 1 prior lines of therapy. Extramedullary disease (EMD) is defined as soft-tissue plasmacytomas NOT arising from skeletal lesions. The maximum diameter of extramedullary lesions should ≥2cm detected by physical exam and confirmed (when required) by Weight Bearing CT/MRI/PET-CT and/or biopsy.
- ECOG score is ≤ 2
- No active infections.
- Negative for HBV-DNA, HCV-RNA, and HIV.
- Liver function meeting the following criteria: Total bilirubin \<1.5 × ULN (patients with Gilbert's syndrome must have total bilirubin \<3 × ULN), ALT and AST \<3 × ULN.
- Renal function meeting the following criteria: Creatinine clearance ≥30mL/min (calculated using the Cockcroft-Gault formula).
- Blood tests conducted within 7 days before screening must meet the following standards: WBC count ≥1.0×10⁹/L, Hemoglobin ≥70g/L, Platelet count ≥75×10⁹/L or ≥50×10⁹/L (if ≥50% plasma cells are present in bone marrow); Or as determined appropriate by the investigator.
- Patients receiving hematopoietic growth factors (e.g., erythropoietin, granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\], and platelet-stimulating factors such as thrombopoietin \[TPO\] or interleukin-11) must stop such treatments at least 2 weeks prior to screening.
- Non-pregnant female patients must confirm pregnancy negativity at screening (via β-hCG serum test or urine pregnancy test).
- Male patients, female patients of childbearing potential, and their partners must agree to use effective contraception during the treatment period and for at least 3 months after CAR-T cell infusion.
- Male patients must agree not to donate sperm, starting from the initial screening period until 90 days after the last dose.
- Patients must agree to comply with study procedures and follow-up visits.
Exclusion Criteria11
- Plasma cell leukemia or solitary plasmacytoma.
- Prior exposure to both BCMA- and GPRC5D-targeted therapies (patients who have received only one of these targeted therapies are eligible for enrollment).
- Evidence of primary or secondary resistance to elotuzumab, carfilzomib, or thalidomide.
- Pregnant or breastfeeding women, or women with pregnancy plans within the next six months.
- Infectious diseases (e.g., HIV, active tuberculosis, etc.).
- Active hepatitis B or hepatitis C infection.
- Abnormal vital signs or inability to cooperate with examinations.
- Mental or psychological disorders preventing compliance with treatment or treatment evaluation.
- Severe allergic constitution or severe allergic history, particularly to aponermin, carfilzomib, thalidomide, dexamethasone or other effective components or excipients of related drugs.
- Significant dysfunction of major organs, such as the heart, lungs, or brain.
- \) Patients with severe autoimmune diseases. 11) Any other reasons deemed unsuitable for participation in this study as determined by the investigator.
Interventions
Autologous BCMA/GPRC5D bispecific CAR-T cells, infusion intravenously at a target dose of 2-4 x 10\^6 anti-BCMA/GPRC5D bispecific CAR-T cells/kg.
Apornemin 10mg/kg will be administered by i.v. infusion. Apornemin will be administered on Days 1-5, 15-19 during bridging therapy, and on Days 1-5 every 28-day cycle during maintanance treatment.
Carfilzomib 27mg/m\^2 will be administered by i.v. on Days 1,2,8,9 during bridging therapy.
Thalidomide (150mg/d) will be administered by p.o. on Days 1-14 during bridging therapy, and Days 1-28 every 28-day cycle during maintanance treatment.
Dexamethasone (20mg/d) will be administered by i.v. or p.o. on Days 1-4,8,9 during bridging therapy.
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06793475