A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL).

Официальное название

A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL)

Обзор

The goal of this clinical trial is to learn if teclistamab in combination with daratumumab (Tec-Dara) works to treat newly diagnosed multiple myeloma with concurrent light chain amyloidosis (MM+AL). It will also learn about the safety of this combination. The main questions it aims to answer are: Does Tec-Dara improve the 1-year progression-free survival rate compared to historical data (50% to 75%) in MM+AL patients? What are the rates of hematologic response (ORR, VGPR, CR, MRD negativity) and organ response in MM+AL patients treated with Tec-Dara? What medical problems do participants have when taking Tec-Dara? Participants will: Receive teclistamab subcutaneous injection with step-up dosing (0.06, 0.3, 1.5 mg/kg), followed by 1.5 mg/kg weekly in Cycle 1, 3.0 mg/kg every 2 weeks in Cycles 2-3, and 3.0 mg/kg every 4 weeks in Cycles 4-24 Receive daratumumab subcutaneous injection 1800 mg weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks in Cycles 7-24 Continue treatment until disease progression, unacceptable toxicity, or a maximum of 24 cycles Undergo disease assessments every 28 days (±7 days) including laboratory tests for hematologic and organ response evaluation Provide bone marrow samples for MRD and RNA sequencing analysis

Вмешательства

• Препарат Teclistamab
  Teclistamab: A humanized IgG4-PAA bispecific antibody targeting BCMA and CD3. It bridges malignant plasma cells and CD3+ T cells, leading to T cell activation and perforin/granzyme-mediated lysis of BCMA+ tumor cells. Daratumumab: A humanized IgG1κ monoclonal antibody targeting CD38, which induces tumor cell lysis through complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. It also enhances T cell-mediated anti-myeloma i

Первичные конечные точки

• 1-Year Progression-Free Survival (PFS) Rate [Срок оценки: From the start of treatment to 1 year, or until disease progression or death, whichever occurs first]

Вторичные конечные точки (9)

• Hematologic Complete Response (Heme-CR) rate [Срок оценки: Up to 24 cycles (approximately 2 years)]
• Very Good Partial Response or Better (≥VGPR) Rate [Срок оценки: Up to 24 cycles (approximately 2 years)]
• Minimal Residual Disease (MRD) Negativity Rate [Срок оценки: 6 months and 12 months, and up to 24 cycles (approximately 2 years)]
• Organ Response Rate [Срок оценки: Up to 24 cycles (approximately 2 years)]
• Time to First Response [Срок оценки: Up to 24 cycles (approximately 2 years)]
• Duration of Response [Срок оценки: Up to 3 years from study start]
• Median Progression-Free Survival [Срок оценки: Up to 3 years from study start]
• Time to Next Treatment [Срок оценки: Up to 3 years from study start]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Срок оценки: Through study completion, up to 12 months after the end of study treatment.]

Критерии участия

Критерии включения

• Age ≥18 years, any sex/gender
• Diagnosis of multiple myeloma according to IMWG criteria
• Histopathologic diagnosis of AL amyloidosis confirmed by:

• Green birefringence under polarized light microscopy with Congo red staining; AND at least one of the following:

• Immunohistochemistry and/or immunofluorescence
• Mass spectrometry
• Electron microscopy/immunoelectron microscopy
• Measurable disease at screening
• Newly diagnosed, no prior anti-plasma cell therapy
• Adequate laboratory values:

• Hemoglobin ≥7.5 g/dL
• Absolute neutrophil count ≥1.0×10⁹/L
• Platelet count ≥70×10⁹/L (platelet transfusion acceptable; >50×10⁹/L if ≥50% bone marrow nucleated cells are plasma cells)
• ALT ≤2.5× upper limit of normal (ULN)
• AST ≤2.5× ULN
• Total bilirubin ≤2.0× ULN
• Creatinine clearance ≥30 mL/min
• Corrected serum calcium ≤14 mg/dL
• Male and female participants of childbearing potential must use at least 2 effective contraceptive methods during the study
• Voluntarily signed informed consent form (ICF)

Критерии исключения

• Prior anti-myeloma therapy or stem cell transplantation
• Diagnosis of monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma, primary AL amyloidosis without concurrent MM, Waldenström macroglobulinemia, plasma cell leukemia, POEMS syndrome, or other malignancies within 3 years prior to enrollment
• Active infection or autoimmune disease
• Uncontrolled diabetes, hypertension, or other comorbidities
• Pregnant or lactating female
• Currently participating in another interventional study
• Any other condition that the investigator considers unsuitable for study participation

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 · 1 центр

• Zhongshan Hospital Fudan University — Шанхай

Идентификаторы

NCT: NCT07638683 · SHZS-MMAL-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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