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).
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)
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
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Peng Liu
- Número de teléfono: +86-021-64041990
- Correo electrónico: liu.peng@zs-hospital.sh.cn
Copia de seguridad de contactos de estudio
- Nombre: Jing Li
- Número de teléfono: +86-18149780650
- Correo electrónico: li.jing6@zs-hospital.sh.cn
Ubicaciones de estudio
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Shanghai, Porcelana
- Reclutamiento
- Zhongshan Hospital Fudan University
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Contacto:
- Jing Li
- Número de teléfono: +86-18149780650
- Correo electrónico: li.jing6@zs-hospital.sh.cn
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Treatment Group
Teclistamab (subcutaneous injection) with step-up dosing: 0.06 mg/kg, 0.3 mg/kg, and 1.5 mg/kg on Days 1, 3, and 5 of Cycle 1, 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. 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. Treatment continues until disease progression, unacceptable toxicity, or a maximum of 24 cycles (approximately 2 years). |
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 immunity by increasing cytotoxic T helper cells and depleting CD38+ immunoregulatory cells, thereby potentiating teclistamab's activity.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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1-Year Progression-Free Survival (PFS) Rate
Periodo de tiempo: From the start of treatment to 1 year, or until disease progression or death, whichever occurs first
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The percentage of participants who are alive and free from disease progression at 1 year after initiation of Tec-Dara treatment.
Progression is defined according to IMWG criteria, including increase in serum M protein, urine M protein, or serum free light chain; development of new bone lesions or soft tissue plasmacytomas; or hypercalcemia.
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From the start of treatment to 1 year, or until disease progression or death, whichever occurs first
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Hematologic Complete Response (Heme-CR) rate
Periodo de tiempo: Up to 24 cycles (approximately 2 years)
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Heme-CR will be defined as: involved free light-chain level less than the upper limit of the normal range with negative serum and urine immunofixation; normalization of the uninvolved free light-chain level or free light-chain ratio will not be required to determine a complete response.
Heme-CR rate is the percentage of participants who achieve CR prior to subsequent anti-myeloma therapy, during or after the study treatment.
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Up to 24 cycles (approximately 2 years)
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Very Good Partial Response or Better (≥VGPR) Rate
Periodo de tiempo: Up to 24 cycles (approximately 2 years)
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Heme-VGPR is defined as a reduction in the dFLC to <40 mg/L.
≥VGPR rate is the percentage of participants achieving VGPR and CR prior to subsequent anti-myeloma therapy during or after the study treatment.
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Up to 24 cycles (approximately 2 years)
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Minimal Residual Disease (MRD) Negativity Rate
Periodo de tiempo: 6 months and 12 months, and up to 24 cycles (approximately 2 years)
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Proportion of participants achieving MRD negativity at a sensitivity threshold of 10^-5, assessed by next-generation flow cytometry (NGF) or next-generation sequencing (NGS).
The MRD-negativity rate by 6 and 12 months will be reported descriptively.
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6 months and 12 months, and up to 24 cycles (approximately 2 years)
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Organ Response Rate
Periodo de tiempo: Up to 24 cycles (approximately 2 years)
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Proportion of participants achieving organ response according to consensus criteria for AL amyloidosis, based on changes in NT-proBNP, cardiac troponin T/I, and estimated glomerular filtration rate (eGFR).
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Up to 24 cycles (approximately 2 years)
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Time to First Response
Periodo de tiempo: Up to 24 cycles (approximately 2 years)
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Time from the start of treatment to the first documented PR or better response according to IMWG criteria.
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Up to 24 cycles (approximately 2 years)
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Duration of Response
Periodo de tiempo: Up to 3 years from study start
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Time from the start of treatment to death from any cause.
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Up to 3 years from study start
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Median Progression-Free Survival
Periodo de tiempo: Up to 3 years from study start
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Time from the start of treatment to disease progression or death from any cause, whichever occurs first.
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Up to 3 years from study start
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Time to Next Treatment
Periodo de tiempo: Up to 3 years from study start
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Time from the start of treatment to the initiation of first subsequent anti-myeloma therapy.
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Up to 3 years from study start
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Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Periodo de tiempo: Through study completion, up to 12 months after the end of study treatment.
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Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0.
A participant with multiple adverse events of the same preferred term will be counted once.
Adverse events will be summarized by frequency, severity (graded by CTCAE v5.0), and causality, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, hematologic toxicities, and infusion-related reactions.
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Through study completion, up to 12 months after the end of study treatment.
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Differential gene expression in bone marrow by RNA sequencing between baseline and disease progression in MM-AL patients.
Periodo de tiempo: Baseline and up to 3 years.
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Bone marrow transcriptome profiles will be analyzed by RNA sequencing at baseline and at disease progression to identify differentially expressed genes, altered signaling pathways, and molecular signatures predictive of disease progression in MM-AL patients.
Data will be summarized as fold-change in gene expression, pathway enrichment scores, and predictive model performance metrics (e.g., AUC, sensitivity, specificity).
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Baseline and up to 3 years.
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Peng Liu, Fudan University
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Neoplasias
- Enfermedades metabólicas
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Enfermedades hematológicas
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Neoplasias De Células Plasmáticas
- Trastornos hemostáticos
- Paraproteinemias
- Trastornos de proteínas en sangre
- Trastornos hemorrágicos
- Deficiencias de proteostasis
- Amilosis
- Enfermedades Nutricionales y Metabólicas
- Enfermedades hemic y linfáticas
- Amiloidosis de cadena ligera de inmunoglobulina
- Mieloma múltiple
- daratumumab
Otros números de identificación del estudio
- SHZS-MMAL-001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- CIF
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
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