Multiple Myeloma
Conditions
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
Interventions
DRUGAVE1642
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
DRUGVelcade
For Part 2 ONLY, fixed dose of 1.3 mg/m² administered on Days 1, 4, 8, and 11.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
France, Italy
Outcome results
None listed