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

• Status: Completed
• Trial end date: 2008-09-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Treatments: Antibodies; Antibodies, Monoclonal; Bortezomib

Criteria

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.