Masitinib in Patients With Mastocytosis With Handicap and Bearing the D816V Mutation

A 12-week With Possible Extension, Prospective, Multicenter, Randomized, Open-label, 2-parallel Group, Phase IIa Study to Compare Efficacy and Safety of AB1010 at 3 or 6 mg/kg/Day in Treatment of Patients With Mastocytosis With Handicap and Bearing Activating Point Mutations in the Phosphotransferase Domain of c-Kit Such as the Main Mutation Asp-816-Val (D816V)

The objective is to compare efficacy and safety of AB1010 at 3 or 6 mg/kg/day in treatment of patients with mastocytosis with handicap and bearing activating point mutations in the phosphotransferase domain of c-Kit such as the main mutation Asp-816-Val (D816V).

Study Overview

• Status: Completed
• Conditions: Mastocytosis
• Intervention / Treatment: Drug: masitinib

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with one of the following documented mastocytosis:

   • Smouldering systemic mastocytosis
   • Indolent systemic mastocytosis with organomegaly
   • Indolent Systemic Mastocytosis having 2 infiltrated organs (skin and bone-marrow)
   • Any mastocytosis with in the last 6 months at least 3 anaphylactic shocks or syncops requiring either use of adrenaline or medical assistance
   • Cutaneous Mastocytosis (CM)

2. Skin biopsy-documented mastocytosis and evaluable disease based upon:

   • Histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin biopsy
   • Clinical criteria: typical skin lesions (maculopapular, urticaria pigmentosa, mastocytoma)
3. Missing data (c-kit molecular analysis not done) or documented presence of an activating point mutation in the phosphotransferase domain of c-kit such as D816V c-kit mutation in at least one infiltrated organ (bone marrow or skin)

4. Refractory to at least one of the symptomatic treatments such as:

   • Anti H1
   • Anti H2
   • Proton pump inhibitor
   • Osteoclast inhibitor
   • Cromoglycate Sodium
   • Antileukotriene
   • Other therapies used for the symptomatic care

5. Handicap defined as at least one of the following handicaps:

   • pruritus score ≥ 6
   • number of flushes per week ≥ 7
   • number of stools per day ≥ 4 ,
   • number of mictions per day ≥ 8 ,
   • QLQ-C30 score ≥ 60,
   • Hamilton score ≥ 10

Exclusion Criteria:

1. Patients 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. Patient with a major surgery within 2 weeks prior to study entry

3. No vulnerable population will be included in this study

   • Life expectancy < 6 months.
   • Patient is < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ.
   • Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
   • Patient has a severe and/or uncontrolled medical disease.
   • Patient has a known diagnosis of human immunodeficiency virus (HIV) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: masitinib 3 mg/kg/day	Drug: masitinib
EXPERIMENTAL: masitinib 6 mg/kg/day	Drug: masitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy on handicaps	Pruritus score at week 12 Number of flushes per week at week 12 Hamilton score at week 12 Fatigue Impact scale at week 12	week 12

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Olivier Lortholary, MD, PhD, Necker Hospital, Paris, France

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (ACTUAL): November 1, 2007
• Study Completion (ACTUAL): May 1, 2010

Study Registration Dates

• First Submitted: December 23, 2010
• First Submitted That Met QC Criteria: December 23, 2010
• First Posted (ESTIMATE): December 24, 2010

Study Record Updates

• Last Update Posted (ACTUAL): December 10, 2018
• Last Update Submitted That Met QC Criteria: December 6, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: mastocytosis; D816V; handicaps
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Hypersensitivity; Neoplasms, Connective Tissue; Immune Complex Diseases; Mastocytosis
• Other Study ID Numbers: AB06013