MRD-Adaptive Guided Immunotherapy With CAR-T for Transplant-Ineligible Patients With Multiple Myeloma

Официальное название

A Prospective, Open-Label, Single-Center Clinical Study of a Fully Immunotherapy-Based Strategy Driven by MRD-Guided Dynamic Risk Stratification in Transplant-Ineligible Newly Diagnosed Multiple Myeloma

Обзор

This is a prospective, single-center, clinical study to evaluate the efficacy and safety of a fully immunotherapy-based strategy guided by MRD-driven dynamic risk stratification in transplant-ineligible patients with newly diagnosed multiple myeloma.

Подробное описание

All subjects will receive standard induction therapy for up to four cycles prior to screening. Following response evaluation, those who meet the inclusion criteria will be enrolled and subsequently stratified into standard-risk and ultra-high-risk groups based on predefined clinical and molecular features.

Patients in the standard-risk group will receive BCMA CAR-T therapy, followed by standard consolidation and maintenance. Patients achieving sustained MRD negativity and stringent complete response (sCR) on two consecutive assessments may enter a treatment-free observation phase. Patients in the ultra-high-risk group will also receive BCMA CAR-T therapy, followed by GPRC5D/CD3 bispecific antibody consolidation and maintenance. Patients achieving sCR and sustained MRD negativity (≥12 months) may enter treatment-free observation. Patients who experience MRD resurgence or loss of response will resume maintenance therapy.

Вмешательства

• Биопрепарат BCMA CAR-T
  Patients will receive single-dose infusion of autologous BCMA-directed CAR-T cellsBCMA CAR-T single dose (3.0 x 10\^6 cells /kg).
• Препарат GPRC5D/CD3 BiTEs
  Patients will receive GPRC5D/CD3 BiTEs maintenance therapy at a dose of 54 μg/kg every 4 weeks, starting 3 months after BCMA CAR-T infusion.

Первичные конечные точки

• Sustained MRD-negative rate [Срок оценки: Up to 2 year]
• Progression free survival (PFS) [Срок оценки: Up to 3 year]

Вторичные конечные точки (3)

• Complete response rate (CRR) [Срок оценки: Up to 2 years]
• MRD negativity rate [Срок оценки: Up to 2 years]
• Overall survival (OS) [Срок оценки: Up to 5 year]

Критерии участия

Критерии включения

• Age ≥ 18 years and ≤ 75 years.
• Participants with documented newly-diagnosed multiple myeloma according to IMWG diagnostic criteria.
• Measurable disease at screening, defined as: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
• Patients deemed ineligible for high-dose chemotherapy with ASCT due to any of the following: Age ≥65 years; Investigator assessment of ineligibility; ECOG performance status 3-4; Repeated failure of hematopoietic stem cell mobilization; Patient's decision to defer ASCT.
• Tumor cells were BCMA and GPRC5D positive.
• Serum total bilirubin <2 x upper limit of normal (ULN), serum AST and ALT <3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).
• Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.

Критерии исключения

• Active amyloidosis.
• Central nervous system involvement.
• Prior BCMA-targeted therapy or CAR-T therapy.
• Active hepatitis B or hepatitis C virus infection.
• Known HIV infection.
• Life expectancy <6 months.
• Woman who are pregnant or breastfeeding.
• Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs.
• Any other conditions that are not eligible for the trial in the judgement of the principal investigator.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Тяньцзинь

Идентификаторы

NCT: NCT07106736 · IIT2025064

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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