Aponermin treatment before CAR-T therapy for 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

This study is testing if aponermin treatment can help multiple myeloma patients with extra tumors feel better before they receive CAR-T therapy.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: elotuzumab, CAR-T
• Locations: 2 sites (Beijing and 1 other locations)
• Trial ID: NCT06793475 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of aponermin-based bridging therapy in patients with relapsed or refractory multiple myeloma who also have extramedullary disease. It is a prospective, single-arm, multicenter, open-label study that involves administering aponermin along with other treatments such as CAR-T therapy, carfilzomib, thalidomide, and dexamethasone. The goal is to assess how well this combination therapy works in managing the disease prior to CAR-T infusion.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory extramedullary multiple myeloma who have undergone at least one prior line of therapy.

Not a fit: Patients with active infections or those who do not meet the specific eligibility criteria for liver and renal function may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with difficult-to-treat multiple myeloma.

How similar studies have performed: While this approach is innovative, it is not clear if similar studies have shown success, as this specific combination therapy has not been widely tested.

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.

Where this trial is running

Beijing and 1 other locations

• Beijing Gobroad Boren Hospital — Beijing, China (RECRUITING)
• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, China (RECRUITING)

Study contacts

• Study coordinator: Gang An, PhD&MD

Conditions: Extramedullary Multiple Myeloma