A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study 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