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

Overview

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

• Biological 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.
• Drug 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.
• Drug Carfilzomib
  Carfilzomib 27mg/m\^2 will be administered by i.v. on Days 1,2,8,9 during bridging therapy.
• 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.
• Drug Dexamethasone
  Dexamethasone (20mg/d) will be administered by i.v. or p.o. on Days 1-4,8,9 during bridging therapy.

Primary outcome measures

• Overall response rate (ORR) [Time frame: within 1 months after BCMA/GPRC5D CAR-T infusion]

Secondary outcome measures (4)

• ORR before CAR-T cell infusion [Time frame: before CAR-T cell infusion]
• Progression free survival(PFS) [Time frame: Up to 2 year]
• Overall Survival (OS) [Time frame: Up to 2 year]
• Adverse events and serious adverse events [Time frame: Up to 2 year]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

9\) Patients with severe autoimmune diseases. 11) Any other reasons deemed unsuitable for participation in this study as determined by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Beijing Gobroad Boren Hospital — Beijing
• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin

Identifiers

NCT: NCT06793475 · IIT2024113

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗