Aponermin-Based Bridging Therapy Prior to CAR-T Infusion in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease

NCT ID: NCT06793475

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-09
• Study Completion Date: 2026-12-31

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.

Conditions

Extramedullary Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aponermin-based regimen bridging CAR-T therapy

Patients will receive aponermin-based bridging therapy followed by Fc-based conditioning and CAR-T cell infusion. One month after CAR-T cell therapy, patients will begin maintenance therapy for at most 6 months or until disease progression, death, intolerance, withdrawal for other reasons, or the study's termination/completion.

Group Type: EXPERIMENTAL

anti-BCMA/GPRC5D bispecific CAR-T

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Carfilzomib 27mg/m\^2 will be administered by i.v. on Days 1,2,8,9 during bridging therapy.

Thalidomide

Intervention Type: DRUG

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

Intervention Type: DRUG

Dexamethasone (20mg/d) will be administered by i.v. or p.o. on Days 1-4,8,9 during bridging therapy.

Interventions

anti-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.

Intervention Type: BIOLOGICAL

Apornemin

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.

Intervention Type: DRUG

Carfilzomib

Carfilzomib 27mg/m\^2 will be administered by i.v. on Days 1,2,8,9 during bridging therapy.

Intervention Type: DRUG

Thalidomide

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.

Intervention Type: DRUG

Dexamethasone

Dexamethasone (20mg/d) will be administered by i.v. or p.o. on Days 1-4,8,9 during bridging therapy.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Gobroad Boren Hospital

Beijing, , China

Site Status: RECRUITING

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Gang An, PhD&MD

Role: CONTACT

angang@ihcams.ac.cn

86-022-23909171

Facility Contacts

Wei Chen

Role: primary

chenwei@gobroadhealthcare.com

008615801145177

Gang An, PhD&MD

Role: primary

angang@ihcams.ac.cn

008613502181109

Other Identifiers

IIT2024113

Identifier Type: -

Identifier Source: org_study_id