Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis

NCT ID: NCT00814073

Last Updated: 2019-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

135 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-31

Study Completion Date

2015-11-30

Brief Summary

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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

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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.

Conditions

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Indolent Systemic Mastocytosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Masitinib & BSC

Masitinib (6 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Group Type EXPERIMENTAL

Masitinib

Intervention Type DRUG

Masitinib 6 mg/kg/day

Best Supportive Care

Intervention Type OTHER

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglicate, antidepressants, leukotriene antagonists, interferon-alpha, 2-CdA, and corticosteroids.

Placebo & BSC

Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo

Best Supportive Care

Intervention Type OTHER

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglicate, antidepressants, leukotriene antagonists, interferon-alpha, 2-CdA, and corticosteroids.

Interventions

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Masitinib

Masitinib 6 mg/kg/day

Intervention Type DRUG

Placebo

Matching placebo

Intervention Type DRUG

Best Supportive Care

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglicate, antidepressants, leukotriene antagonists, interferon-alpha, 2-CdA, and corticosteroids.

Intervention Type OTHER

Other Intervention Names

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AB1010

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AB Science

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olivier Lortholary, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Necker, Paris, France

Locations

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UC Davis Health System , Department of Dermatology

Sacramento, California, United States

Site Status

MD Anderson Cancer Centre

Houston, Texas, United States

Site Status

CHU d'Amiens

Amiens, , France

Site Status

Hôpital Avicenne

Bobigny, , France

Site Status

CHU de Brest

Brest, , France

Site Status

CHU de Caen

Caen, , France

Site Status

CHU Clermont Ferrand

Clermont-Ferrand, , France

Site Status

Hôpital Claude Huriez

Lille, , France

Site Status

CHU Dupuytren

Limoges, , France

Site Status

Hôpital Ambroise Paré

Marseille, , France

Site Status

Hôpital Nord

Marseille, , France

Site Status

Hôpital Central

Nancy, , France

Site Status

CHU Hôtel Dieu

Nantes, , France

Site Status

Hôpital l'Archet II

Nice, , France

Site Status

Hôpital Necker

Paris, , France

Site Status

Hôpital Tenon

Paris, , France

Site Status

CHU Lyon Sud

Pierre-Bénite, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

CHU Milétrie

Poitiers, , France

Site Status

CHU Hôpital Sud

Rennes, , France

Site Status

CHU de Saint-Etienne

Saint-Etienne, , France

Site Status

Hôpital Purpan

Toulouse, , France

Site Status

Hôpital Bretonneau

Tours, , France

Site Status

Hôpital des Hauts Clos

Troyes, , France

Site Status

Countries

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United States France

References

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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.

Reference Type BACKGROUND
PMID: 28069280 (View on PubMed)

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.

Reference Type RESULT
PMID: 28069279 (View on PubMed)

Related Links

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Other Identifiers

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AB06006

Identifier Type: -

Identifier Source: org_study_id

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