Clinical trial NCT00814073: Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis
Official title: Randomized, Placebo-controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib at 6 mg/kg/Day to Placebo in Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Indolent Systemic Mastocytosis
Keywords: Mastocytosis with handicap
Mastocytosis
Mast cell
Mast cell infiltration
Skin
Bone marrow
Pruritus
Flushes
c-kit
c-kit mutation
Wild Type
Mutation Asp-816-Val(D816V)
Indolent systemic mastocytosis
smoldering systemic mastocytosis
Lead sponsor: AB Science
Sponsor class: INDUSTRY
First posted: 2008-12-23
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cumulative response (4R75%)
timeFrame: 24 weeks
Secondary outcomes:
measure: Cumulative response (3R75%)
timeFrame: 24 weeks
measure: Cumulative response (2R75%)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Health System , Department of Dermatology
state: California
city: Houston
country: United States
facility: MD Anderson Cancer Centre
state: Texas
city: Amiens
country: France
facility: CHU d'Amiens
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Brest
country: France
facility: CHU de Brest
city: Caen
country: France
facility: CHU de Caen
city: Clermont Ferrand
country: France
facility: CHU Clermont Ferrand
city: Lille
country: France
facility: Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU Dupuytren
city: Marseille
country: France
facility: Hôpital Ambroise Paré
city: Marseille
country: France
facility: Hôpital Nord
city: Nancy
country: France
facility: Hôpital Central
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Nice
country: France
facility: Hôpital l'Archet II
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital Tenon
city: Pierre Bénite
country: France
facility: CHU Lyon Sud
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU Milétrie
city: Rennes
country: France
facility: CHU Hôpital Sud
city: Saint-Etienne
country: France
facility: CHU de Saint-Etienne
city: Toulouse
country: France
facility: Hôpital Purpan
city: Tours
country: France
facility: Hôpital Bretonneau
city: Troyes
country: France
facility: Hôpital des Hauts Clos
Study officials:
affiliation: Hôpital Necker, Paris, France
name: Olivier Lortholary, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arock M. A new therapeutic advance for symptomatic systemic mastocytosis? Lancet. 2017 Feb 11;389(10069):576-578. doi: 10.1016/S0140-6736(16)31655-5. Epub 2017 Jan 7. No abstract available.
citation: Lortholary O, Chandesris MO, Bulai Livideanu C, Paul C, Guillet G, Jassem E, Niedoszytko M, Barete S, Verstovsek S, Grattan C, Damaj G, Canioni D, Fraitag S, Lhermitte L, Georgin Lavialle S, Frenzel L, Afrin LB, Hanssens K, Agopian J, Gaillard R, Kinet JP, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017 Feb 11;389(10069):612-620. doi: 10.1016/S0140-6736(16)31403-9. Epub 2017 Jan 7.