- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01233895
Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma
Open Label Study of the Anti Insulin-like Growth Factor 1 Receptor (IGF-1R) Monoclonal Antibody, AVE1642, as Single Agent (Dose Escalation, Part 1) and in Combination With Velcade® (Combination, Part 2) in Patients With Recurrent, Refractory Multiple Myeloma (MM)
Primary Objectives:
Study Part 1: Determine the selected dose of AVE1642 administered every 3 weeks based on pharmacokinetic (PK) (Clearance of AVE1642), pharmacodynamic (PD) (insulin-like growth factor 1 [IGF-1] serum level) parameters, and eventual dose limiting toxicities (DLTs) in patients with recurrent, refractory multiple myeloma (MM).
Study Part 2: Assess the safety of the combination of the selected dose of AVE1642 with the recommended dose of Velcade®.
Secondary Objectives :
Study Part 1:
- To assess the safety profile: type, incidence and intensity of drug related adverse events (AEs)
- To assess the biological activity of AVE1642 (saturation of the receptors and down-regulation) on malignant plasma cells and on peripheral blood mononuclear cells (PBMC) and granulocytes
- To assess the biological activity of AVE1642 on the signalization pathway of the IGF-1 system (phosphorylated akt [pAkt], phosphorylated erk [pErk]) on malignant plasma cells when technically possible
- To define PK profile of AVE1642, and its PD effects on serum IGF 1, GF 2 and IGFBP-3
- To assess clinical efficacy (complete response [CR], partial response [PR], minimal response [MR] and stabilization) based on the European group for Blood and Marrow Transplantation (EBMT) criteria, when possible
- To assess potential immunogenicity by detection of human antihumanized antibodies (HAHA) anti-AVE1642
Study Part 2:
- To detect any PK or PD interaction between AVE1642 and Velcade®
- To assess clinical efficacy (CR, PR, MR, no change [NC]) according to EBMT criteria when appropriate
- To assess biological activity of AVE1642 in combination with Velcade® on malignant plasma cells collected from bone marrow aspirates: saturation and down-regulation of the insulin-like growth factor 1 receptor (IGF-1R) and activity on the signalization pathway of the IGF-1 system (pAkt, pErk) when feasible
- To detect immunogenicity reaction (HAHA)
- To characterize PK and PD profile of a low dose (0.5 mg/kg) of AVE1642 expected to be non biologically active
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Lille, Francia, 59037
- Sanofi-Aventis Investigational Site Number 250002
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Nantes, Francia, 44093
- Sanofi-Aventis Investigational Site Number 250001
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Vandoeuvre Les Nancy, Francia, 54511
- Sanofi-Aventis Investigational Site Number 250003
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Torino, Italia, 10126
- Sanofi-Aventis Investigational Site Number 380001
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Multiple myeloma confirmed by bone marrow aspirate or biopsy
- Patient had to have relapsed and/or refractory multiple myeloma after at least 1 standard therapy, and have demonstrated disease progression
- Previous exposure to Velcade was allowed, provided no DLTs of Grade 3 or above had been observed during previous treatment (for Part 2 of the study only)
Exclusion Criteria:
- Prior therapy with any IGF-1 system targeting compound
- History of allogenic stem cell transplantation in case of concomitant immunosuppressive therapy within 6 months before study entry. Patients having undergone autologous stem cell transplantation(s) may have been included in the study
- History of organ transplant and any patient receiving long term systemic immunosuppressive therapy
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- 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: AVE1642/ AVE1642 with Velcade
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For Part 1, AVE1642 was administered on Day 1 and then every three weeks intra-venously with the dose escalation step starting at 3 mg/kg/infusion with a classical dose escalation schema of 3+3.
For Part 2, AVE1642 was administered at doses ranging from 0.5 mg/kg to 12 mg/kg
For Part 2 ONLY, fixed dose of 1.3 mg/m² administered on Days 1, 4, 8, and 11.
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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definition of the Selected Dose (SD)
Periodo de tiempo: 2 years
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Selected Dose will be based on the AVE1642 clearance /IGF-1 plateaus and on safety (less than 33% of pts with dose limiting toxicity (DLT)when administered as single agent in a first part of the study.
The safety and pharmacokinetics of the regimen in combination with bortezomib will be assessed in the second part of the study
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2 years
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Assess the efficacy (complete, partial, minimal responses and stabilizations)
Periodo de tiempo: 2 years
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According to the European Group for Blood and Marrow Transplantation (EBMT) criteria when appropriate (e.g.
baseline M Protein, % Plasma Cells in Bone Marrow,skeletal disease status and at least one evaluable post-baseline assessment)
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2 years
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Pharmacokinetic drug interaction between AVE1642 and Velcade (part 2)
Periodo de tiempo: Day 22
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Day 22
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Neoplasias
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Enfermedades hematológicas
- Trastornos hemorrágicos
- Trastornos hemostáticos
- Paraproteinemias
- Trastornos de proteínas en sangre
- Mieloma múltiple
- Neoplasias De Células Plasmáticas
- Agentes antineoplásicos
- Bortezomib
Otros números de identificación del estudio
- TED6420
- AVE1642A/1001 (Otro identificador: other sanofi-aventis reference)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre AVE1642
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SanofiTerminadoCarcinoma de hígadoFrancia
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SanofiTerminadoNeoplasias de mamaFrancia, Italia, España