Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma
- Registration Number
- NCT01233895
- Lead Sponsor
- Sanofi
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
- 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)
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AVE1642/ AVE1642 with Velcade Velcade - AVE1642/ AVE1642 with Velcade AVE1642 -
- Primary Outcome Measures
Name Time Method definition of the Selected Dose (SD) 2 years 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
- Secondary Outcome Measures
Name Time Method Assess the efficacy (complete, partial, minimal responses and stabilizations) 2 years 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)
Pharmacokinetic drug interaction between AVE1642 and Velcade (part 2) Day 22
Trial Locations
- Locations (4)
Sanofi-Aventis Investigational Site Number 250002
🇫🇷Lille, France
Sanofi-Aventis Investigational Site Number 250003
🇫🇷Vandoeuvre Les Nancy, France
Sanofi-Aventis Investigational Site Number 380001
🇮🇹Torino, Italy
Sanofi-Aventis Investigational Site Number 250001
🇫🇷Nantes, France