The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V).

Inclusion Criteria:

1. 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)

2. 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)

3. 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)

4. 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

5. 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:

1. 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)

2. Patient with a major surgery within 2 weeks prior to study entry

3. 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