Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis with handicaps MedDRA version: 9.1 Level: LLT Classification code 10026891 Term: Mastocytosis
Conditions
Interventions
Product Name: AB1010 Tablets
Product Code: AB1010 Tablets
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Sponsors
AB SCIENCE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient with one of the following documented mastocytosis as per WHO classification: ? Smouldering Systemic Mastocytosis ? Indolent Systemic Mastocytosis ? Cutaneous Mastocytosis 2. Patient with documented mastocytosis and evaluable disease based upon histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin and/or bone marrow biopsy 3. Patient with documented treatment failure of his/her handicap(s) with at least one of the following therapy used at optimized dose (refer to table 2): ? Anti H1 ? Anti H2 ? Proton pump inhibitor ? Osteoclast inhibitor ? Cromoglycate Sodium ? Antileukotriene 4. Handicapped status defined as at least two of the following handicaps, including at least one among pruritus, flushes, depression and asthenia: ? pruritus score = 6 ? number of flushes per week = 7 ? Hamilton rating scale (depression) = 10 ? number of stools per day = 4 , ? number of mictions per day = 8 , ? Fatigue Impact Scale total score (asthenia) = 40 5. Patients with OPA > 2 (moderate to intolerable general handicap) 6. ECOG = 2 7. Patient with adequate organ function : ? absolute neutrophil count (ANC) = 2.0 x 109/L, ? platelets (PTL) = 100 x 109/L ? AST/ALT = 2.5x ULN (= 5 x ULN in case of liver mast cell involvement), ? bilirubin = 1.5x ULN ? creatinin = 1.5 x ULN ? albumin > 0.75 x LLN ? urea = 1.5 x ULN ? negative proteinuria defined as negative dipstick; in case of the positive dipstick , 24 hours proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patient with one of the following mastocytosis: ? Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD) ? Mast cell leukemia (MCL) ? Aggressive systemic mastocytosis (ASM) 2. Previous treatment with any Tyrosine Kinase Inhibitor 3. Patient who had major surgery within 2 weeks prior to screening visit 4. Vulnerable population defined as : ? Life expectancy < 6 months ? Patient with < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ ? Patient with grade III/IV cardiac conditions as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study) ? Patient with any severe and/or uncontrolled medical condition ? Patient with known diagnosis of human immunodeficiency virus (HIV) infection 5. 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 6. Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment 7. Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline 8. Treatment with any investigational agent within 4 weeks prior to baseline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to compare the safety and efficacy of masitinib to placebo in patients with mastocytosis with handicap. Primary endpoint: ? Responder rate at week 24 ; Secondary Objective: Secondary endpoints: ? Response in at least two out of three variables among pruritus, flushes, depression or asthenia, at week 12 and week 24 ? Responder rate at week 12 ? Pruritus score at week 12 and week 24 ? Number of flushes per week at week 12 and week 24 ? Hamilton score at week 12 and week 24 ? Fatigue Impact Scale at week 12 and week 24 ? Number of mictions per day at week 12 and week 24 ? Number of stools per day at week 12 and week 24 ? QLQ-C30 scores at week 12 and week 24 ? Overall Patient Assessment (OPA) at week 12 and week 24 ? AFIRMM V2 score at week 12 and week 24 ? Percentage of patient without handicap at week 12 and 24 ? Mast cell infiltration in the skin or bone marrow at week 24 ? Serum tryptase level at week 24 Safety profile of masitinib: Occurrence of Adverse Events, vital signs, EKG, Chest X-Ray, cardiac ultrasonography and biological parameters. ; Primary end point(s): Primary variable: Responder rate A patient is classified as responder if he/she presents an improvement of = 50% in at least one handicap, handicap being defined as a score above the cut in any of the 4 variables: - pruritus score = 6, - number of flushes per week = 7, - Hamilton score = 10, - Fatigue Impact Scale score = 40. Any patient with a worsening of more than 50% of any handicap, and/or with emergence of a new handicap with an increase of more th | — |
Countries
Austria, Bulgaria, Czech Republic, France, Germany, Greece, Hungary, Italy, Latvia, Slovakia, Spain, United Kingdom
Outcome results
None listed