Patient case: 39-year-old female with melanoma; genetic feature: KIT (N822Y)

Clinical trial: A Phase 3 Study to Compare Efficacy and Safety of Masitinib to Placebo in the Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

Summary: The objective of this study is to compare the safety and efficacy of masitinib (AB1010) to placebo in patients with mastocytosis with handicap.

Detailed description: Mastocytosis is a disease characterized by mast cell invasion in various organs. Mast cells are bone marrow derived cells which produce histamine and other substances causing allergic and anaphylactic reactions. Accumulation of mast cells in body organs can inhibit the functionality of the organ and eventually cause degeneration.
  Mutations of the mast cell growth factor receptor (KIT protein, the product of the c-Kit proto-oncogene) might be found in patients with mastocytosis.
  Masitinib (AB1010) is a tyrosine kinase inhibitor (TKI), selectively and effectively inhibiting c-kit. Its effect may include inhibition of cell proliferation, inhibition of cell cycle progression and induction of apoptosis resulting in the reduction of mast cell accumulation in body tissues. This drug is thereby specific to mastocytosis and active in slowing or reducing the number of mast cells particularly in aggressive forms of the disease.

Eligibility: Inclusion Criteria:
  1. Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis, Cutaneous 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 asthenia: pruritus score ≥ 6, number of flushes per week ≥ 7, Hamilton rating scale (depression) ≥ 10, number of stools per day ≥ 4, number of mictions per day ≥ 8, Fatigue Impact Scale total score (asthenia) ≥ 40
  5. Patients with OPA > 2 (moderate to intolerable general handicap)
  6. Male or female patient with age ≥ 18 years
  Exclusion Criteria:
  1. Patient 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. Previous treatment with any Tyrosine Kinase Inhibitor
  3. Patient presenting with at least one of the following feature: ischemic heart disease, cardiac failure, conduction disorders or arrythmia
  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

Relevance to patient case: not relevant