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

NCT01233895 | Completed Phase 1

• 2 other identifiers: TED6420AVE1642A/1001
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 4

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

Outcome Measures

Primary Outcomes (1)

• definition of the Selected Dose (SD)

  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

  2 years

Secondary Outcomes (2)

• Assess the efficacy (complete, partial, minimal responses and stabilizations)

  2 years

• Pharmacokinetic drug interaction between AVE1642 and Velcade (part 2)

  Day 22

Study Arms (1)

AVE1642/ AVE1642 with Velcade

EXPERIMENTAL

Drug: AVE1642; Drug: Velcade

Interventions

AVE1642 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

AVE1642/ AVE1642 with Velcade

Velcade DRUG

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

Also known as: Bortezomib

AVE1642/ AVE1642 with Velcade

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Sanofi-Aventis Investigational Site Number 250002

Lille, 59037, France

Location

Sanofi-Aventis Investigational Site Number 250001

Nantes, 44093, France

Location

Sanofi-Aventis Investigational Site Number 250003

Vandœuvre-lès-Nancy, 54511, France

Location

Sanofi-Aventis Investigational Site Number 380001

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

AVE1642; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 29, 2010
• First Posted: November 3, 2010
• Study Start: September 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: November 3, 2010

Record last verified: 2010-10

Locations

IT (1); FR (3)