Extramedullary Multiple Myeloma
Conditions
Brief 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.
Interventions
BIOLOGICALanti-BCMA/GPRC5D bispecific CAR-T
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.
DRUGApornemin
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.
DRUGCarfilzomib
Carfilzomib 27mg/m\^2 will be administered by i.v. on Days 1,2,8,9 during bridging therapy.
DRUGThalidomide
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.
DRUGDexamethasone
Dexamethasone (20mg/d) will be administered by i.v. or p.o. on Days 1-4,8,9 during bridging therapy.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be informed and voluntarily sign the Informed Consent Form (ICF). 2. Age ≥18 years. 3. Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines) 4. 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. 5. ECOG score is ≤ 2 6. No active infections. 7. Negative for HBV-DNA, HCV-RNA, and HIV. 8. 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. 9. Renal function meeting the following criteria: Creatinine clearance ≥30mL/min (calculated using the Cockcroft-Gault formula). 10. 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. 11. 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. 12. Non-pregnant female patients must confirm pregnancy negativity at screening (via β-hCG serum test or urine pregnancy test). 13. 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. 14. Male patients must agree not to donate sperm, starting from the initial screening period until 90 days after the last dose. 15. Patients must agree to comply with study procedures and follow-up visits.
Exclusion criteria
1. Plasma cell leukemia or solitary plasmacytoma. 2. Prior exposure to both BCMA- and GPRC5D-targeted therapies (patients who have received only one of these targeted therapies are eligible for enrollment). 3. Evidence of primary or secondary resistance to elotuzumab, carfilzomib, or thalidomide. 4. Pregnant or breastfeeding women, or women with pregnancy plans within the next six months. 5. Infectious diseases (e.g., HIV, active tuberculosis, etc.). 6. Active hepatitis B or hepatitis C infection. 7. Abnormal vital signs or inability to cooperate with examinations. 8. Mental or psychological disorders preventing compliance with treatment or treatment evaluation. 9. Severe allergic constitution or severe allergic history, particularly to aponermin, carfilzomib, thalidomide, dexamethasone or other effective components or excipients of related drugs. 10. Significant dysfunction of major organs, such as the heart, lungs, or brain. 9\) Patients with severe autoimmune diseases. 11) Any other reasons deemed unsuitable for participation in this study as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | within 1 months after BCMA/GPRC5D CAR-T infusion | The definition of ORR is the proportion of participants who achieve a PR or better as the best response according to the IMWG criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR before CAR-T cell infusion | before CAR-T cell infusion | ORR before CAR-T cell infusion is defined as the proportion of participants who achieve a confirmed PR or better as the best response after conditioning treatment but prior to CAR-T cell infusion. |
| Progression free survival(PFS) | Up to 2 year | Progression free survival is defined as the time from the start of Aponermin treatment to disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 2 year | Overall Survival (OS) is defined as the time from the start of Aponermin treatment to the date of the participant's death. |
| Adverse events and serious adverse events | Up to 2 year | Adverse events (AEs), serious adverse events (SAEs), and assessments of clinical laboratory values |
Countries
China
Contacts
Primary ContactGang An, PhD&MD
Outcome results
None listed