A study to compare masitinib in combination with bortezomib and dexamethasone to placebo in in combination with bortezomib and dexamethasone in the treatment of patients with relapsing multiple myeloma who have received one therapy in the past

• Register: EUCTR
• Last refreshed on: 14 August 2012
• Main ID: EUCTR2009-017930-35-IT
• Date of registration: 29/03/2012
• Prospective Registration: No
• Primary sponsor: AB SCIENCE
• Public title: A study to compare masitinib in combination with bortezomib and dexamethasone to placebo in in combination with bortezomib and dexamethasone in the treatment of patients with relapsing multiple myeloma who have received one therapy in the past
• Scientific title: A prospective, multicenter, randomised, double-blind, placebocontrolled, 2-parallel group, phase 3 study to compare 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 received one previous therapy - not applicable
• Date of first enrolment: 05/10/2011
• Target sample size: 300
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017930-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Czech Republic, France, Germany, Greece, Italy, Korea, Democratic People's Republic of, Spain, United States

Contacts

• Name: Clinical Project Manager
• Affiliation: AB Science

• Name: Clinical Project Manager
• Affiliation: AB Science

Key inclusion & exclusion criteria

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 1) to one previous line of treatment (defined in Table 2). Patients previously treated, with Bortezomib, for multiple myeloma can be included if and only if : o they have shown minimal, partial or complete response to this treatment o they have not been refractory to this treatment (to be considered as bortezomib refractory patient, any patient who didn’t show any response to previous bortezomib treatment or whose disease progressed during or within 60 days of bortezomib treatment) 3. Patient candidate for receiving the standard therapy (bortezomib and dexamethazone) 4. Patient with measurable progressive disease defined by at least one of the following two measurements: • Serum M-protein 1 g/dL • Urine M-protein ³ 200 mg/24h 5. Patient with ECOG 2 6. Patient with adequate organ function • Absolute neutrophil count (ANC) 1.5 giga/L • Platelets (PTL) 75 x 109/L • AST/ALT 2.5 ULN • Creatinin clearance > 30 mL/min • Bilirubin 1.5 ULN • Albumin 1 x LLN • Urea 2 x ULN • Albuminuria 300 mg/day 7. Patient with life expectancy > 6 months 8. Man or non-pregnant non-lactating woman, age >18 years and weight > 40 Kg and BMI > 18 kg/m² 9. Man and woman of childbearing potential, (entering the study after a menstrual period and who have a negative pregnancy test) must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. 10. Patient able and willing to comply with study procedures as per protocol 11. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Patient with peripheral neuropathy Grade >2 2. Patient with hypersensitivity to bortezomib, boron or dexamethazone 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 randomisation 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) 7. Patient with acute diffuse infiltrative pulmonary and pericardial disease 8. Patient treated for a cancer other than multiple myeloma within five years before enrolment, with the exception of basal cell carcinoma and cervical cancer in situ 9. Patient with central nervous system (CNS) metastasis or with history of CNS metastasis 10. Patient with one of the following cardiac conditions: • Patient with recent cardiac history (within 6 months) of: - Acute coronary syndrome - Acute heart failure (class III or IV of the NYHA classification) - Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death) • Patient with cardiac failure class III or IV of the NYHA classification • Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block) • Syncope without known aetiology within 3 months • Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension 11. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent Previous treatments 12. High dose of corticosteroids and/or local irradiation should be stopped at least 2 weeks prior to Baseline 13. Administration of any other treatment for multiple myeloma should be stopped at least 4 weeks prior to Baseline. Patients who received bortezomib within 6 months prior to Baseline are excluded 14. Treatment with any investigational agent should be stopped at least 4 weeks prior to Baseline 15. Patient eligible for bone-marrow transplantation as second line therapy


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

relapsing multiple myeloma after one previous therapy
MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: masitinib mesylate
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: masitinib
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: NA
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

Primary Outcome(s)

Primary end point(s): Primary endpoint Overall Progression Free Survival (PFS) according to International Myeloma Working Group criteria 2009 (IMWG / revised Bladé criteria).

Main Objective: Objectives The objective is to compare the efficacy and safety of masitinib 6 mg/kg/day to placebo in the treatment of patients with relapsing multiple myeloma who have received one previous therapy. Patients will receive study treatment (masitinib/placebo) with the standard therapy: bortezomib (Velcade) and dexamethazone. Primary endpoint Overall Progression Free Survival (PFS) according to International Myeloma Working Group criteria 2009 (IMWG / revised Bladé criteria)

Secondary Objective: 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 12, 24, 36, 48, 64 and 72 - ECOG Performance Status at week 12, 24, 36, 48, 64 and 72 - Bone pain Verbal Rating Score (VRS) at week 12, 24, 36, 48, 64 and 72 - Analgesic (non-opioid) consumption at week 12, 24, 36, 48, 64 and 72 - Opioid consumption at week 12, 24, 36, 48, 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(s)

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 12, 24, 36, 48, 64 and 72 - ECOG Performance Status at week 12, 24, 36, 48, 64 and 72 - Bone pain Verbal Rating Score (VRS) at week 12, 24, 36, 48, 64 and 72 - Analgesic (non-opioid) consumption at week 12, 24, 36, 48, 64 and 72 - Opioid consumption at week 12, 24, 36, 48, 64 and 72 • Safety assessments: - Safety profile using the NCI CTC v4.02 classification

Timepoint(s) of evaluation of this end point: TTP: date of documeted progression; TTNT: date of initiation of a new line of treatment due to progression; OS: documented death; QOL: see paragraph above

Secondary ID(s)

2009-017930-35-FR

AB06002

Source(s) of Monetary Support

AB Science