Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis
The objective of this study is to compare the safety and efficacy of masitinib (AB1010) to
 placebo in patients with mastocytosis with handicap.
This was a prospective, multicenter, randomized, placebo-controlled, parallel-group, phase 3
 study, conducted in 15 countries, evaluating the efficacy and safety of masitinib (6
 mg/kg/day administered orally in two daily intakes over 24-weeks with a double-blind
 extension period possible) for the treatment of indolent systemic mastocytosis, smoldering
 mastocytosis or cutaneous mastocytosis, in patients with mast cells mediator release symptoms
 that are refractory to conventional symptomatic treatment.

 A study protocol amendment restricted enrolment to patients with severe indolent and
 smoldering systemic mastocytosis. The objective of this phase 3 study was therefore to
 evaluate masitinib efficacy and safety in severe systemic mastocytosis patients, with or
 without D816V mutation of c-Kit. The primary objective of the phase 3 study was to detect a
 statistically significant difference between masitinib (plus optimal concomitant symptomatic
 treatments) and placebo (plus optimal concomitant symptomatic treatments) in cumulative
 response on four severe symptoms, referred to also as handicaps.
Inclusion Criteria:

 1. Patient with one of the following documented mastocytosis as per WHO classification:
 Smouldering Systemic Mastocytosis, Severe Indolent Mastocytosis

 2. Patient with documented mastocytosis and evaluable disease based upon histological
 criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin
 and/or bone marrow biopsy

 3. Patient with documented treatment failure of his/her handicap(s) with at least one of
 the following therapy used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor,
 Osteoclast inhibitor, Cromoglycate Sodium, Antileukotriene

 4. Handicapped status defined as at least two of the following handicaps, including at
 least one among pruritus, flushes, depression and fatigue: pruritus score ≥ 9, number
 of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19,
 number of stools per day ≥ 4, number of mictions per day ≥ 8, Fatigue Impact Scale
 total score (asthenia) ≥ 75

 5. Patients with OPA ≥ 2 (moderate to intolerable general handicap)

 6. ECOG ≤ 2

 7. Patient with adequate organ function

 Exclusion Criteria:

 1. Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Not documented
 Smouldering Systemic Mastocytosis or Indolent Systemic Mastocytosis, Systemic
 Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease
 (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)

 2. Previous treatment with any Tyrosine Kinase Inhibitor

 3. Patient with recent cardiac history of: Acute coronary syndrome, Acute heart failure,
 Significant ventricular arrhythmia; patient with cardiac failure class III or IV;
 Syncope without known aetiology within 3 months, uncontrolled severe hypertension.

 4. Patient with any condition that the physician judges could be detrimental to subjects
 participating in this study; including any clinically important deviations from normal
 clinical laboratory values or concurrent medical events Previous treatment

 5. Change in the symptomatic treatment of mastocytosis or administration of any new
 treatment of mastocytosis within 4 weeks prior to baseline

 6. Treatment with any investigational agent within 4 weeks prior to baseline