A study to compare masitinib in combination with bortezomib and dexamethazone to placebo in combination with bortezomib and dexamethazone in the treatment of patients with relapsing multiple myeloma

INTERVENTION: Product Name: masitinib Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: masitinib mesylate CAS Number: 790‐299‐79‐5 Current Sponsor code: AB1010 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ INN or Proposed INN: masitinib mesylate CAS Number: 790‐299‐79‐5 Current Sponsor code: AB1010 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Multiple Myeloma relapsing after one previous line therapy ; MedDRA version: 16.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15] PRIMARY OUTCOME: Main Objective: The objective is to compare the efficacy and safety of masitinib 6 mg/kg/day in combination with bortezomib and dexamethazone to placebo in combination with bortezomib and dexamethazone in the treatment of patients with relapsing multiple myeloma who have received one previous therapy.; ; Primary endpoint:; Overall Progression Free Survival (PFS) according to International Myeloma Working Group criteria 2009 (IMWG / revised Bladé criteria); Primary end point(s): Overall Progression Free Survival (PFS) according to International Myeloma Working Group criteria 2009 (IMWG / revised Bladé criteria) Secondary Objective: •Disease progression; ‐Overall Time to Progression according to International Myeloma Working Group criteria 2009 (revised Bladé criteria); ‐Time To Next Treatment; •Survival; ‐Overall Survival; •Response; ‐Best Response rate during study according to International Myeloma Working Group criteria 2009 (revised Bladé criteria); •Quality of life assessment; ‐Quality of Life according to the EORTC QLQ‐C30 questionnaire at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72; ‐ECOG Performance Status at week 0 (screening), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72; ‐Bone pain Verbal Rating Score at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72; ‐Analgesic (non‐opioid) consumption at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72; ‐Opioid consumption at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72; •Safety assessments ; ‐Safety profile using the NCI CTC v4.02 classification; Timepoint(s) of evaluation of this end point: date of documented progression or death during the study SECONDARY OUTCOME: Secondary end point(s): Secondary endpoints ; • Disease progression: ; ‐ Overall Time to Progression (TTP) according to International Myeloma Working Group criteria 2009 (IMWG / revised Bladé criteria) ; ‐ Time To Next Treatment (TTNT) ; • Survival: ; ‐ Overall Survival (OS) ; • Response: ; ‐ Best Response rate during study according to International Myeloma Working Group criteria 2009 (IMWG / revised Bladé criteria) ; • Quality of life assessment: ; ‐ Quality of Life according to the EORTC QLQ‐C30 questionnaire at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72 ; ‐ ECOG Performance Status at week 0 (screening), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72 ; ‐ Bone pain Verbal Rating Score (VRS) at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72 ; ‐ Analgesic (non‐opioid) consumption at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72 ; ‐ Opioid consumption at week 0 (baseline), 3, 6, 9, 12, 15, 18, 21, 24, 32, 40, 48, 56, 64 and 72 ; • Safety assessments: ; ‐ Safety profile using the NCI CTC v4.02 classification (including adverse events, laboratory values, vital signs, and physical examination including ECG). ; Timepoint(s) of evaluation of this end point: TTP: date of documented progression; TTNT: date of initiation of a new line of treatment due to prpgression; OS; documented death; QOL: see paragraph above 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: o Hypercalcemia: serum calcium > 11.5 mg/100 ml or o Renal insufficiency: serum creatinine > 173 µmol/l o Anemia: normochromic, normocytic with a hemoglobin value of > 2g/100 ml below the lower limit of normal or a hemoglobin value < 10g/100 ml o 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) (defined in Table 5) to one previous line of treatment (defined in Table 6). Patients previously treated, with Bortezomib, for multiple myeloma can be