Clinical trial NCT06793475: Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Extramedullary Multiple Myeloma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2025-01-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: within 1 months after BCMA/GPRC5D CAR-T infusion
Secondary outcomes:
measure: ORR before CAR-T cell infusion
timeFrame: before CAR-T cell infusion
measure: Progression free survival(PFS)
timeFrame: Up to 2 year
measure: Overall Survival (OS)
timeFrame: Up to 2 year
measure: Adverse events and serious adverse events
timeFrame: Up to 2 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad Boren Hospital
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Study officials:
References: