A Phase 3 Study to Compare Efficacy and Safety of Masitinib to Placebo in the Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by AB Science
Sponsor:
Information provided by (Responsible Party):
AB Science
ClinicalTrials.gov Identifier:
NCT00814073
First received: December 22, 2008
Last updated: September 25, 2012
Last verified: September 2012
  Purpose

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


Condition Intervention Phase
Smouldering Systemic Mastocytosis
Indolent Systemic Mastocytosis
Cutaneous Mastocytosis With Handicap
Mastocytosis
Drug: masitinib (AB1010)
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 24-week With Possible Extension, Prospective, Multicentre, Randomized, Double Blind, Placebo-controlled, 2-parallel Group With a Randomization 1:1, Phase III 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

Resource links provided by NLM:


Further study details as provided by AB Science:

Primary Outcome Measures:
  • Responder rate at week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: December 2008
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
masitinib (AB1010) 6 mg/kg/day per os
Drug: masitinib (AB1010)
masitinib (AB1010) 6 mg/kg/day per os
Other Name: AB1010
Placebo Comparator: 2
placebo
Drug: placebo
matching placebo

Detailed Description:

Mastocytosis is a disease characterized by mast cell invasion in various organs. Mast cells are bone marrow derived cells which produce histamine and other substances causing allergic and anaphylactic reactions. Accumulation of mast cells in body organs can inhibit the functionality of the organ and eventually cause degeneration.

Mutations of the mast cell growth factor receptor (KIT protein, the product of the c-Kit proto-oncogene) might be found in patients with mastocytosis.

Masitinib (AB1010) is a tyrosine kinase inhibitor (TKI), selectively and effectively inhibiting c-kit. Its effect may include inhibition of cell proliferation, inhibition of cell cycle progression and induction of apoptosis resulting in the reduction of mast cell accumulation in body tissues. This drug is thereby specific to mastocytosis and active in slowing or reducing the number of mast cells particularly in aggressive forms of the disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis, Cutaneous 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 asthenia: pruritus score ≥ 6, number of flushes per week ≥ 7, Hamilton rating scale (depression) ≥ 10, number of stools per day ≥ 4, number of mictions per day ≥ 8, Fatigue Impact Scale total score (asthenia) ≥ 40
  5. Patients with OPA > 2 (moderate to intolerable general handicap)
  6. Male or female patient with age ≥ 18 years

Exclusion Criteria:

  1. Patient with one of the following 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 presenting with at least one of the following feature: ischemic heart disease, cardiac failure, conduction disorders or arrythmia
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814073

Contacts
Contact: Olivier Lortholary, M.D., Ph.D. +33 (0)1 44 38 15 70 olivier.lortholary@nck.aphp.fr

Locations
United States, California
UC Davis Health System , Department of Dermatology Recruiting
Sacramento, California, United States, 95816
Contact: LIU Fu-Tong, MD         
United States, Texas
MD Anderson Cancer Centre Recruiting
Houston, Texas, United States, 77030
France
CHU d'Amiens Recruiting
Amiens, France
Hôpital Avicenne Recruiting
Bobigny, France
CHU de Brest Recruiting
Brest, France
CHU de Caen Recruiting
Caen, France
CHU Clermont Ferrand Not yet recruiting
Clermont Ferrand, France, 63000
Hôpital Claude Huriez Recruiting
Lille, France
CHU Dupuytren Recruiting
Limoges, France
Hôpital Nord Recruiting
Marseille, France
Hôpital Ambroise Paré Recruiting
Marseille, France
Hôpital Central Recruiting
Nancy, France
CHU Hôtel Dieu Recruiting
Nantes, France
Hôpital l'Archet II Recruiting
Nice, France
Hôpital Tenon Recruiting
Paris, France
Hôpital Necker Recruiting
Paris, France
CHU Lyon Sud Not yet recruiting
Pierre Bénite, France, 69495
Centre Hospitalier Lyon Sud Recruiting
Pierre-Bénite, France
CHU Milétrie Recruiting
Poitiers, France
CHU Hôpital Sud Recruiting
Rennes, France
CHU de Saint-Etienne Recruiting
Saint-Etienne, France
Hôpital Purpan Recruiting
Toulouse, France
Hôpital Bretonneau Recruiting
Tours, France
Hôpital des Hauts Clos Recruiting
Troyes, France
Sponsors and Collaborators
AB Science
Investigators
Principal Investigator: Olivier Lortholary, MD, PhD Hôpital Necker, Paris, France
  More Information

No publications provided

Responsible Party: AB Science
ClinicalTrials.gov Identifier: NCT00814073     History of Changes
Other Study ID Numbers: AB06006
Study First Received: December 22, 2008
Last Updated: September 25, 2012
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by AB Science:
Mastocytosis with handicap
Mastocytosis
Smouldering systemic mastocytosis
Indolent systemic mastocytosis
Cutaneous mastocytosis
Mast cell
Mast cell infiltration
Skin
Bone marrow
Pruritus
Flushes
c-kit
c-kit mutation
Wild Type
Mutation Asp-816-Val(D816V)

Additional relevant MeSH terms:
Mastocytosis
Urticaria Pigmentosa
Mastocytosis, Systemic
Mastocytosis, Cutaneous
Mastocytoma
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Skin Diseases
Pigmentation Disorders

ClinicalTrials.gov processed this record on August 28, 2014