A 24-week with possible extension study to compare efficacy and safety of masitinib to placebo in treatment of patients with Smouldering or Indolent Severe Systemic mastocytosis
- Conditions
- Smouldering or Indolent Severe Systemic mastocytosisTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2016-001447-39-FR
- Lead Sponsor
- AB SCIENCE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 140
1.Patient with one of the following documented mastocytosis:
?Smouldering Systemic Mastocytosis (SSM)
?Indolent Systemic Mastocytosis (ISM)
2.Patients meet the retained classification of SM based on the presence of one of the three criteria and an excess of mast cells or a presence of abnormal mast cells in at least two organs (first one is skin and the second being bone-marrow or GI Tract):
I.Bone marrow biopsy and/or aspirate associated with at least a sign of abnormality of mast cells:
a)Abnormal aggregates of mast cells in a sample in bone marrow:
The criteria is deemed satisfied if the aggregate i) is quantified and is strictly above 15 mast cells per aggregated (corresponding to WHO major criterion), or ii) is not quantified but is described as nodule, seat, cluster, focus, or granuloma and therefore pathological;
b)=25% atypical mast cells in a sample of bone marrow (corresponding to WHO minor criterion);
c)c-Kit point mutation at codon 816 in bone marrow (corresponding to WHO minor criterion);
d)Abnormal mast cells in the sample of bone marrow while microscopic testing that can be described by the following words: Spindled; Abnormal; Atypical; Fusiform; Dystrophic; Pathologic; Dysmorphic (corresponding to WHO minor criterion);
e)Abnormal immunohistochemistry signs: mast cells in bone marrow express CD2 or/and CD25 present (corresponding to WHO minor criterion);
f)Abnormal infiltration of mast cells in the bone marrow:
The criteria is deemed satisfied if the infiltration i) is quantified and is strictly above 3% in the biopsy, or ii) is not quantified but is abnormal as described with infiltration, contingent of mast cells, or proliferation and therefore pathological.
II.Detection of c-kit 816 in the bone marrow without evidence of mast cells in bone marrow but with evidence of c-Kit 816 in skin, justifying clonality;
III.Excess of mast cells in digestive organs.
3.Patient with severe symptoms over the 14-day run-in period defined as at least one of the following:
?Pruritus score = 9
?Number of flushes per week = 8
?Hamilton rating scale for depression (HAMD-17) score = 19
4.Patient with documented treatment failure of his/her symptom (s) (within last two years) with at least two of the failure symptomatic treatment used at optimized dose (Minimal duration of each treatment should be at least 8 weeks):
?Anti H1
?Anti H2
?Proton pump inhibitor
?Antidepressants
?Cromoglycate Sodium
?Antileukotriene
5.Patients must be on a stable dose of Anti-H1 for a minimum of 4 weeks before screening and should remain at a stable dose throughout the study period. For other symptomatic treatments, if the patient takes corticosteroids, Anti-H2 or PPI or Antidepressants or Cromoglycate Sodium or Antileucotriene, the treatment must have started at least 4 weeks before Screening and must be stable throughout the study.
6.Documented age between 18 to 75 years (inclusive).
Are the trial subjects under 18? no
Number of subjects
1.Cutaneous mastocytosis, SM associated with hematological neoplasm, Mast Cell Leukemia and Aggressive SM.
2.Previous treatment with any Tyrosine Kinase Inhibitor.
3.Any change in the symptomatic treatment of SM, including the systemic corticosteroids, or administration of any new treatment for SM within 4 weeks prior to screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The study objective is to compare the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from documented Smouldering or Indolent Severe Systemic mastocytosis with handicap unresponsive to optimal symptomatic treatment;Secondary Objective: Not applicable ;<br> Primary end point(s): Cumulative response on 3 severe symptoms (Pruritus, Flush, Depression) from week 8 to week 24.<br> Severe symptomd for primary objective is defined as: Pruritus score = 9, number of Flushes per week = 8, Depression = 19.<br> <br> Response on a severe symptoms is defined as an improvement = 75% for Pruritus, Flushes and Depression.<br> <br> In case of rescue medication to manage a severe symptom, all subsequent measures will be considered as fail”.<br> ;Timepoint(s) of evaluation of this end point: Every 4 weeks from week 8
- Secondary Outcome Measures
Name Time Method