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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Mastocytosis

Intervention / Treatment
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* Drug: masitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: masitinib 3 mg/kg/day<br>masitinib 3 mg/kg/day | Drug: masitinib<br> <br> |
| Experimental: masitinib 6 mg/kg/day<br>masitinib 6 mg/kg/day | Drug: masitinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy on handicaps | Pruritus score at week 12 Number of flushes per week at week 12 Hamilton score at week 12 Fatigue Impact scale at week 12 | week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mastocytosis, D816V, handicaps