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Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis (AB06006)

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ClinicalTrials.gov Identifier: NCT00814073
Recruitment Status : Completed
First Posted : December 23, 2008
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
AB Science

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.

Condition or disease Intervention/treatment Phase
Indolent Systemic Mastocytosis Drug: Masitinib Drug: Placebo Other: Best Supportive Care Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : December 2008
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015


Arm Intervention/treatment
Experimental: Masitinib & BSC
Masitinib (6 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Drug: Masitinib
Masitinib 6 mg/kg/day
Other Name: AB1010

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.

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




Primary Outcome Measures :
  1. Cumulative response (4R75%) [ Time Frame: 24 weeks ]
    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).


Secondary Outcome Measures :
  1. Cumulative response (3R75%) [ Time Frame: 24 weeks ]
    Cumulative response in at least one of three severe baseline symptoms (pruritus, flushes, or depression)

  2. Cumulative response (2R75%) [ Time Frame: 24 weeks ]
    Cumulative response in at least one of three severe baseline symptoms (pruritus or flushes)



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00814073


Locations
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United States, California
UC Davis Health System , Department of Dermatology
Sacramento, California, United States, 95816
United States, Texas
MD Anderson Cancer Centre
Houston, Texas, United States, 77030
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, 63000
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, 69495
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, France
Sponsors and Collaborators
AB Science
Investigators
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Principal Investigator: Olivier Lortholary, MD, PhD Hôpital Necker, Paris, France

Additional Information:
Publications of Results:
Other Publications:
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Responsible Party: AB Science
ClinicalTrials.gov Identifier: NCT00814073     History of Changes
Other Study ID Numbers: AB06006
First Posted: December 23, 2008    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AB Science:
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
Additional relevant MeSH terms:
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Mastocytosis
Mastocytosis, Systemic
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Diseases
Immune Complex Diseases
Hypersensitivity
Immune System Diseases