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

Sanofi

Status and phase

Completed

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: AVE1642

Drug: Velcade

Study type

Interventional

Funder types

Industry

Identifiers

NCT01233895

TED6420

AVE1642A/1001 (Other Identifier)

Details and patient eligibility

About

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

Enrollment

26 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.