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

NCT ID: NCT01233895

Last Updated: 2010-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2008-09-30

Brief 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

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AVE1642/ AVE1642 with Velcade

Group Type: EXPERIMENTAL

AVE1642

Intervention Type: DRUG

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

Velcade

Intervention Type: DRUG

For Part 2 ONLY, fixed dose of 1.3 mg/m² administered on Days 1, 4, 8, and 11.

Interventions

AVE1642

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

Intervention Type: DRUG

Velcade

For Part 2 ONLY, fixed dose of 1.3 mg/m² administered on Days 1, 4, 8, and 11.

Intervention Type: DRUG

Other Intervention Names

Bortezomib

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

sanofi-aventis

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Investigational Site Number 250002

Lille, , France

Sanofi-Aventis Investigational Site Number 250001

Nantes, , France

Sanofi-Aventis Investigational Site Number 250003

Vandœuvre-lès-Nancy, , France

Sanofi-Aventis Investigational Site Number 380001

Torino, , Italy

Countries

France; Italy

Other Identifiers

AVE1642A/1001

Identifier Type: OTHER

Identifier Source: secondary_id

TED6420

Identifier Type: -

Identifier Source: org_study_id