Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma

Summary

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

Timeline

Start

2006-09

Primary completion

2008-09

Completion

2008-09

Drugs

Indications