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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (4)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

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

Идентификаторы

NCT: NCT06793475 · IIT2024113

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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