Clinical trial NCT01233895: Study of AVE1642 Anti-IGF1R Monoclonal Antibody in Patients With Advanced Multiple Myeloma
Official title: Open Label Study of the Anti Insulin-like Growth Factor 1 Receptor (IGF-1R) Monoclonal Antibody, AVE1642, as Single Agent (Dose Escalation, Part 1) and in Combination With Velcade® (Combination, Part 2) in Patients With Recurrent, Refractory Multiple Myeloma (MM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-11-03
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: definition of the Selected Dose (SD)
timeFrame: 2 years
Secondary outcomes:
measure: Assess the efficacy (complete, partial, minimal responses and stabilizations)
timeFrame: 2 years
measure: Pharmacokinetic drug interaction between AVE1642 and Velcade (part 2)
timeFrame: Day 22
Other outcomes:
Locations:
city: Lille
country: France
facility: Sanofi-Aventis Investigational Site Number 250002
city: Nantes
country: France
facility: Sanofi-Aventis Investigational Site Number 250001
city: Vandoeuvre Les Nancy
country: France
facility: Sanofi-Aventis Investigational Site Number 250003
city: Torino
country: Italy
facility: Sanofi-Aventis Investigational Site Number 380001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: