Isatuximab-VRd in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients

Официальное название

A Single-Arm, Multicenter, Prospective, Observational Clinical Study on the Efficacy and Safety of Isatuximab Combined With Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRd) Regimen in Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TI-NDMM) Patients

Обзор

Primary Objective of the trial is to evaluate the efficacy and safety of Isa-VRd-based regimen in transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) patients receiving treatment in real-world clinical practice in China. And Secondary Objectives is， To assess the MRD negativity rate in Chinese TI-NDMM patients treated with Isa-VRd To assess the safety and tolerability of Isa-VRd in Chinese TI-NDMM patients Participants will: Receive Isatuximab 10 mg/kg iv * Cycle 1: Every weeks on Days 1, 8, 15, and 22 * Cycles 2-8: Every 2 weeks on Days 1 and 15 Receive Bortezomib subcutaneous injection 1.3 mg/m² * Cycles 1-8: Days 1, 8, and 15 of each cycle Receive Lenalidomide oral 25 mg/day * Cycles 1-8: Days 1-21 at 25 mg/day (10 mg/day for patients with creatinine clearance \[CrCl\] ≥30 and \<60 mL/min) Receive Dexamethasone oral 20 mg * Cycles 1-8: Days 1, 8, 15, and 22 of each cycle Following Cycle 8, the investigator may assess and adjust the treatment regimen During the induction phase, efficacy assessment is recommended at each treatment cycle. Patients who achieve ≥CR at the end of induction are recommended to undergo the first MRD monitoring assessment. During the maintenance phase, efficacy assessment is recommended at least every 3 cycles. Patients are recommended to undergo MRD status monitoring (≥CR) every 6 months (i.e., at months 14, 20, and 26) for MRD assessment. During the follow-up period, MRD status monitoring (≥CR) is recommended every 12 months to observe the depth of response.

Подробное описание

This is a single-arm, multicenter, prospective observational cohort study with a planned total enrollment of 333 transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) patients aged ≥18 years old in China. All enrolled participants will receive the Isa-VRd induction regimen for 8 cycles (4 weeks per cycle, total 32 weeks). After induction therapy, investigators will determine whether patients continue maintenance treatment based on individual response status, followed by a 2-year long-term follow-up period from the initiation of Isa-VRd treatment, with the maximum observation window of each subject capped at 24 months.

For efficacy evaluation, minimal residual disease (MRD) testing with a cutoff of NGF=10-⁵ will be performed at multiple prespecified time points: at month 8 post-induction, and every 6 months throughout the maintenance and follow-up phase (at months 14, 20 and 26). The primary endpoint of this study is ≥CR rate after induction therapy. Secondary efficacy endpoints include stringent complete response (sCR), very good partial response (VGPR), overall response rate (ORR), duration of response (DOR), time to response (TTR), time to next treatment (TNT), progression-free survival (PFS), overall survival (OS), as well as all safety and tolerability outcomes.

Throughout the entire treatment and follow-up period, all treatment-emergent adverse events (TEAEs), grade ≥3 adverse events, serious adverse events (SAEs), and adverse events of special interest (AESIs, including infusion reactions and second primary malignancies) will be continuously collected and recorded to evaluate the real-world safety profile of the Isa-VRd regimen in Chinese TI-NDMM patients. The overall planned study duration spans approximately 24 months from the first subject's enrollment to the completion of the last patient's 24-month follow-up assessment.

Вмешательства

• Препарат Isatuximab
  Isatuximab 10 mg/kg Intravenous (IV) infusion * Cycle 1: Every weeks on Days 1, 8, 15, and 22 * Cycles 2-8: Every 2 weeks on Days 1 and 15 Following Cycle 8, the investigator may assess and adjust the treatment regimen Prior to administration of this product, premedication should be given 15-60 minutes before use: acetaminophen 650 mg to 1000 mg orally, H2 receptor antagonist, and diphenhydramine 25 mg to 50 mg intravenously or orally.
• Препарат Bortezomib
  Bortezomib subcutaneous injection 1.3 mg/m² • Cycles 1-8: Days 1, 8, and 15 of each cycle Following Cycle 8, the investigator may assess and adjust the treatment regimen
• Препарат Lenalidomide
  Lenalidomide oral 25 mg/day • Cycles 1-8: Days 1-21 at 25 mg/day (10 mg/day for patients with creatinine clearance \[CrCl\] ≥30 and \<60 mL/min) Following Cycle 8, the investigator may assess and adjust the treatment regimen
• Препарат Dexamethasone
  Dexamethasone oral 20 mg • Cycles 1-8: Days 1, 8, 15, and 22 of each cycle Following Cycle 8, the investigator may assess and adjust the treatment regimen

Первичные конечные точки

• ≥CR rate after induction treatment [Срок оценки: After completion of 8 cycles of induction treatment (approximately 32 weeks or 8 months)]

Вторичные конечные точки (9)

• MRD negativity rate [Срок оценки: At the end of induction phase (Week 32 / approximately 8 months)]
• ≥VGPR rate [Срок оценки: At the end of induction phase (Week 32 / approximately 8 months)]
• Overall response rate [Срок оценки: At the end of induction phase (Week 32 / approximately 8 months)]
• Duration of Response [Срок оценки: From the date of first confirmed response (≥PR) to the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 48 months.]
• Time to Response [Срок оценки: Time from the start date of Isa-VRd treatment to the date of first confirmed response (≥PR) as assessed by investigator， assessed up to 24 months]
• Duration of Treatment [Срок оценки: Time from the start date of Isa-VRd treatment to the date of discontinuation of Isa-VRd regimen for any reason，assessed up to 24 months]
• Progression free survival [Срок оценки: Time from the start date of Isa-VRd treatment to disease progression (as assessed according to 2016 IMWG criteria) or death from any cause, whichever occurs first，assessed up to 48 months]
• Overall Survival [Срок оценки: Time from the start date of Isa-VRd treatment to death from any cause，assessed up to 48 months]
• Incidence Adverse Events [Срок оценки: From the start date of Isa-VRd treatment through study completion, assessed up to 24 months.]

Критерии участия

Критерии включения

• Age ≥18 years
• Newly diagnosed transplant-ineligible multiple myeloma patients as assessed by investigator, specifically referring to CSCO guidelines
• Must meet corresponding laboratory test results (refer to restrictions in package inserts of combination drugs):

• Absolute neutrophil count (ANC) ≥1.0×10⁹/L
• Platelet count ≥50×10⁹/L
• Calculated creatinine clearance ≥30 mL/min (using Cockcroft-Gault formula)
• Total bilirubin ≤3× upper limit of normal (ULN)
• TI-NDMM patients intended for Isa-VRd regimen treatment as determined by investigator judgment, independent of study objectives Signed informed consent form (by patient or their legal representative)

Критерии исключения

• Patients currently participating in other interventional clinical studies
• Patients with known severe hypersensitivity reactions to Isatuximab or any other excipients
• Severe bacteremia at the time of administration
• Currently uncontrolled cardiovascular disease, including:

• Uncontrolled hypertension
• Uncontrolled arrhythmia
• Uncontrollable congestive heart failure
• Unstable angina
• Patients with peripheral neuropathy ≥Grade 2
• Active infectious disease, known human immunodeficiency virus (HIV) positivity, active hepatitis B or hepatitis C
• Patients who are currently pregnant
• Patients who, at the physician's discretion, are unable to tolerate any drug in the combination regimen

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 13 центров

• Peking Union Medical College Hospital — Пекин
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Shenzhen People's Hospital — Шэньчжэнь
• The First Affiliated Hospital of Guangxi Medical University — Naning
• Harbin Institute of Hematologic Oncology — Харбин
• Henan Cancer Hospital — Чжэнчжоу
• Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology. — Ухань
• Jiangsu Provincial People's Hospital — Нанкин
• … и ещё 5 центров

Идентификаторы

NCT: NCT07663253 · B2026-229

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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