Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis

NCT00814073 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: AB06006
• Study Type: interventional
• Target: 135
• Locations: 2 countries
• Sites: 24

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.

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

Outcome Measures

Primary Outcomes (1)

• Cumulative response (4R75%)

  The prospectively declared primary endpoint (4R75%) was cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response was defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).

  24 weeks

Secondary Outcomes (2)

• Cumulative response (3R75%)

  24 weeks

• Cumulative response (2R75%)

  24 weeks

Study Arms (2)

Masitinib & BSC

EXPERIMENTAL

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

Drug: Masitinib; Other: Best Supportive Care

Placebo & BSC

PLACEBO COMPARATOR

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

Drug: Placebo; Other: Best Supportive Care

Interventions

Masitinib DRUG

Masitinib 6 mg/kg/day

Also known as: AB1010

Masitinib & BSC

Placebo DRUG

Matching placebo

Placebo & BSC

Best Supportive Care 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.

Masitinib & BSC; Placebo & BSC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis, Severe Indolent Mastocytosis
• 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
• 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
• 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
• Patients with OPA ≥ 2 (moderate to intolerable general handicap)
• ECOG ≤ 2
• Patient with adequate organ function

You may not qualify if:

• 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)
• Previous treatment with any Tyrosine Kinase Inhibitor
• 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.
• 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
• Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline
• Treatment with any investigational agent within 4 weeks prior to baseline

Sponsors & Collaborators

• AB Science: lead

Study Sites (24)

UC Davis Health System , Department of Dermatology

Sacramento, California, 95816, United States

Location

MD Anderson Cancer Centre

Houston, Texas, 77030, United States

Location

CHU d'Amiens

Amiens, France

Location

Hôpital Avicenne

Bobigny, France

Location

CHU de Brest

Brest, France

Location

CHU de Caen

Caen, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

Hôpital Claude Huriez

Lille, France

Location

CHU Dupuytren

Limoges, France

Location

Hôpital Ambroise Paré

Marseille, France

Location

Hôpital Nord

Marseille, France

Location

Hôpital Central

Nancy, France

Location

CHU Hôtel Dieu

Nantes, France

Location

Hôpital l'Archet II

Nice, France

Location

Hôpital Necker

Paris, France

Location

Hôpital Tenon

Paris, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

CHU Milétrie

Poitiers, France

Location

CHU Hôpital Sud

Rennes, France

Location

CHU de Saint-Etienne

Saint-Etienne, France

Location

Hôpital Purpan

Toulouse, France

Location

Hôpital Bretonneau

Tours, France

Location

Hôpital des Hauts Clos

Troyes, France

Location

Related Publications (2)

• 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.

  PMID: 28069280 BACKGROUND

• 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.

  PMID: 28069279 RESULT

Related Links

• Publication of results

MeSH Terms

Conditions

Mastocytosis, Systemic; Mastocytosis; Pruritus; Blushing; Piebaldism

Interventions

masitinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nonverbal Communication; Communication; Behavior; Albinism; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Olivier Lortholary, MD, PhD

  Hôpital Necker, Paris, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2008
• First Posted: December 23, 2008
• Study Start: December 1, 2008
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 3, 2019

Record last verified: 2019-11

Locations

US (2); FR (22)