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

NCT06793475 | Recruiting

• 1 other identifier: IIT2024113
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  The definition of ORR is the proportion of participants who achieve a PR or better as the best response according to the IMWG criteria.

  within 1 months after BCMA/GPRC5D CAR-T infusion

Secondary Outcomes (4)

• ORR before CAR-T cell infusion

  before CAR-T cell infusion

• Progression free survival(PFS)

  Up to 2 year

• Overall Survival (OS)

  Up to 2 year

• Adverse events and serious adverse events

  Up to 2 year

Study Arms (1)

Aponermin-based regimen bridging CAR-T therapy

EXPERIMENTAL

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.

Biological: anti-BCMA/GPRC5D bispecific CAR-T; Drug: Apornemin; Drug: Carfilzomib; Drug: Thalidomide; Drug: Dexamethasone

Interventions

anti-BCMA/GPRC5D bispecific CAR-T 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.

Aponermin-based regimen bridging CAR-T therapy

Apornemin 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.

Aponermin-based regimen bridging CAR-T therapy

Carfilzomib DRUG

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

Aponermin-based regimen bridging CAR-T therapy

Thalidomide 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.

Aponermin-based regimen bridging CAR-T therapy

Dexamethasone DRUG

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

Aponermin-based regimen bridging CAR-T therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (2)

Beijing Gobroad Boren Hospital

Beijing, China

RECRUITING

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

Tianjin, China

RECRUITING

MeSH Terms

Interventions

carfilzomib; Thalidomide; Dexamethasone

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Gang An, PhD&MD

CONTACT

86-022-23909171; angang@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 27, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 14, 2025

Record last verified: 2024-12

Locations

CN (2)