Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation

Inclusion criteria

• Patients with one of the following documented mastocytosis:

• Smouldering systemic mastocytosis
• Indolent systemic mastocytosis with organomegaly
• Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow)
• Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance
• Cutaneous Mastocytosis (CM)
• Skin biopsy-documented mastocytosis and evaluable disease based upon:

• Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy
• Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma)
• Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin)
• Refractory to at least one of the symptomatic treatments such as:

• Anti H1
• Anti H2
• Proton pump inhibitor
• Osteoclast inhibitor
• Cromoglycate Sodium
• Antileukotriene
• Other therapies used for the symptomatic care
• Handicap defined as at least one of the following handicaps:

• pruritus score ≥ 6
• number of flushes per week ≥ 7
• number of stools per day ≥ 4 ,
• number of mictions per day ≥ 8 ,
• QLQ-C30 score ≥ 60,
• Hamilton score ≥ 10

Exclusion criteria

• Patients 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)
• Patient with a major surgery within 2 weeks prior to study entry
• No vulnerable population will be included in this study

• Life expectancy < 6 months.
• Patient is < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ.
• 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 of study)
• Patient has a severe and/or uncontrolled medical disease.
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection