Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis

Indolent Systemic Mastocytosis Clinical Trial

— AB06006  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00814073
• Other study ID #: AB06006
• Status: Completed
• Phase: Phase 3
• Start date: December 2008
• Est. completion date: November 2015

Study information

• Verified date: November 2019
• Source: AB Science
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Indolent Systemic Mastocytosis
• Mastocytosis

Intervention

Drug:
• Masitinib
Masitinib 6 mg/kg/day
• Placebo
Matching placebo

Other:
• 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.

Locations

Country	Name	City	State
France	CHU d'Amiens	Amiens
France	Hôpital Avicenne	Bobigny
France	CHU de Brest	Brest
France	CHU de Caen	Caen
France	CHU Clermont Ferrand	Clermont Ferrand
France	Hôpital Claude Huriez	Lille
France	CHU Dupuytren	Limoges
France	Hôpital Ambroise Paré	Marseille
France	Hôpital Nord	Marseille
France	Hôpital Central	Nancy
France	CHU Hôtel Dieu	Nantes
France	Hôpital l'Archet II	Nice
France	Hôpital Necker	Paris
France	Hôpital Tenon	Paris
France	CHU Lyon Sud	Pierre Bénite
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	CHU Milétrie	Poitiers
France	CHU Hôpital Sud	Rennes
France	CHU de Saint-Etienne	Saint-Etienne
France	Hôpital Purpan	Toulouse
France	Hôpital Bretonneau	Tours
France	Hôpital des Hauts Clos	Troyes
United States	MD Anderson Cancer Centre	Houston	Texas
United States	UC Davis Health System , Department of Dermatology	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
AB Science

Countries where clinical trial is conducted

United States,  France, 

References & 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cumulative response (3R75%)	Cumulative response in at least one of three severe baseline symptoms (pruritus, flushes, or depression)	24 weeks
Secondary	Cumulative response (2R75%)	Cumulative response in at least one of three severe baseline symptoms (pruritus or flushes)	24 weeks

External Links

•   Publication of results