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 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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2009-017930-35-FR
• Date of registration: 12/03/2010
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: 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 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
• Scientific title: 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 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
• Date of first enrolment: 29/06/2010
• Target sample size: 300
• Recruitment status: Not Recruiting
• 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: no; 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, France, Germany, Greece, Hungary, Italy, Spain, United Kingdom

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 > 1.73 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) 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
4. Patient with ECOG = 2
5. 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 = 0.75 x LLN
• Urea = 1.5 x ULN
• Albuminuria = 300 mg/day
6. Patient with life expectancy > 6 months
7. Man or non-pregnant non-lactating woman, age >18 years and weight > 40 Kg
8. 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.
9. Patient able and willing to comply with study procedures as per protocol
10. 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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 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)
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 grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within 6 months before baseline)
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
12. Patient with any condition or concurrent medical events, including any clinically significant deviations from reference ranges in laboratory test, that, according to the physician, could be detrimental to the subjects who participate

Previous treatments:
13. High dose of corticosteroids and/or local irradiation should be stopped at least 2 weeks prior to Baseline
14. 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
15. Treatment with any investigational agent should be stopped at least 4 weeks prior to Baseline


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

Health Condition(s) or Problem(s) studied

Multiple Myeloma relapsing after one previous line therapy
MedDRA version: 12.1 Level: LLT Classification code 10028228 Term: Multiple myeloma

Intervention(s)

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

Primary Outcome(s)

Main Objective: The objective is to compare the efficacy and safety of masitinib 9 mg/kg/day in combination with bortezomib (Velcade®) 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)

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, 60 and 72
- ECOG Performance Status at week 12, 24, 36, 48, 60 and 72
- Karnofsky Performance Status at week 12, 24, 36, 48, 60 and 72
- Bone pain Verbal Rating Score (VRS) at week 12, 24, 36, 48, 60 and 72
- Analgesic (non-opioid) consumption at week 12, 24, 36, 48, 60 and 72
- Opioid consumption at week 12, 24, 36, 48, 60 and 72

• Safety assessments:
- Safety profile using the NCI CTC v4.02 classification

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

Secondary ID(s)

AB06002

Ethics review

Status: Approved
Approval date:
Contact: