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Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis (AB06006)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00814073
Recruitment Status : Completed
First Posted : December 23, 2008
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
AB Science

Tracking Information
First Submitted Date  ICMJE December 22, 2008
First Posted Date  ICMJE December 23, 2008
Last Update Posted Date December 3, 2019
Study Start Date  ICMJE December 2008
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2008)
Responder rate at week 24 [ Time Frame: 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Cumulative response (3R75%) [ Time Frame: 24 weeks ]
    Cumulative response in at least one of three severe baseline symptoms (pruritus, flushes, or depression)
  • Cumulative response (2R75%) [ Time Frame: 24 weeks ]
    Cumulative response in at least one of three severe baseline symptoms (pruritus or flushes)
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2008)
Response in mastocytosis variables (pruritus, flushes, depression or asthenia), mictions and stools per day, patient score and assessments, patients without handicap, mast cell infiltration , serum tryptase level, safety profile [ Time Frame: 24 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Indolent Systemic Mastocytosis
Intervention  ICMJE
  • Drug: Masitinib
    Masitinib 6 mg/kg/day
    Other Name: AB1010
  • 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.
Study Arms  ICMJE
  • Experimental: Masitinib & BSC
    Masitinib (6 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
    Interventions:
    • Drug: Masitinib
    • Other: Best Supportive Care
  • Placebo Comparator: Placebo & BSC
    Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
    Interventions:
    • Drug: Placebo
    • Other: Best Supportive Care
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 30, 2018)
135
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2008)
200
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00814073
Other Study ID Numbers  ICMJE AB06006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AB Science
Study Sponsor  ICMJE AB Science
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Olivier Lortholary, MD, PhD Hôpital Necker, Paris, France
PRS Account AB Science
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP