A Phase 3 Study to Evaluate Efficacy and Safety of Masitinib in Patients With Relapse or Refractory Multiple Myeloma

• Overall Time to Progression [ Time Frame: time from the date of randomization to the date of documented progression during the study ] [ Designated as safety issue: No ]
• Overall Survival [ Time Frame: Until death ] [ Designated as safety issue: No ]

The purpose of the study is to compare the efficacy and safety of masitinib 6 mg/kg/day in combination with bortezomib and dexamethasone to placebo in combination with bortezomib and dexamethasone in the treatment of patients with relapsing multiple myeloma who have received one previous therapy.

This is a prospective, multicenter, randomized, double-blind, placebo-controlled, 2-parallel group, phase 3 study to compare efficacy and safety of masitinib 9 mg/kg/day to placebo in the treatment of patients with relapsing multiple myeloma who received one previous therapy.

Patients will receive study treatment (masitinib/placebo) with the standard therapy (bortezomib and dexamethazone).

• Drug: masitinib 6 mg/kg/day
  masitinib 6 mg/kg/day
  Other Name: masitinib 6 mg/kg/day with Bortezomib & Dexamethasone
• Drug: placebo
  matching placebo
  Other Name: placebo in combination with Bortezomib and Dexamethasone

• Experimental: masitinib 6 mg/kg/day
  masitinib in combination with Bortezomib and Dexamethasone
  Intervention: Drug: masitinib 6 mg/kg/day
• Placebo Comparator: placebo
  placebo in combination with Bortezomib and Dexamethasone
  Intervention: Drug: placebo

Inclusion Criteria:

1. Patient with confirmed multiple myeloma requiring systemic therapy. All three criteria must be met:

   • Clonal bone marrow plasma cells > 10%
   • Presence of serum and/or urinary monoclonal protein

   • Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

     • Hypercalcemia: serum calcium > 11.5 mg/100 ml or
     • Renal insufficiency: serum creatinine > 173 µmol/l
     • Anemia: normochromic, normocytic with a hemoglobin value of > 2g/100 ml below the lower limit of normal or a hemoglobin value < 10g/100 ml
     • Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
2. Patient with multiple myeloma relapsing according to the International uniform response criteria for multiple myeloma (IMWG 2009/ revised Bladé criteria) to one previous line of treatment

3. Patient with measurable progressive disease defined by at least one of the following two measurements:

   • Serum M-protein ≥ 1 g/dL
   • Urine M-protein ≥ 200 mg/24h

Exclusion Criteria:

1. Patient with peripheral neuropathy Grade >2
2. Patient with hypersensitivity to bortezomib, boron or dexamethasone
3. Patient whose disease progressed during or within 60 days of bortezomib treatment or of any other Multiple Myeloma therapy
4. Patient who received bortezomib within 6 months of randomization to this study
5. Past discontinuation of bortezomib due to associated grade 3 or higher adverse event
6. Patient with contra-indication to high dose of steroids (including ongoing active infection, use of live vaccines, virosis such as hepatitis, herpes, varicella, herpes zoster)