Clinical trial · Interventional

Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment

Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment

NCT04333108CI-TRIAL-00066153unknownPhase 3ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Indolent Systemic Mastocytosis	Indolent Systemic Mastocytosis	ONTOLOGY_EXACT	0.98

Interventions

Interventions (3)

Intervention	Type	Mapped drug	Match
Best Supportive Care	Other	—	UNRESOLVED
Masitinib	Drug	Masitinib	ALIAS
Placebo	Other	—	UNRESOLVED

Design

Arms and outcomes

Arms (2)

type
EXPERIMENTAL
label
Masitinib & BSC
description
Experimental Arm: Masitinib (titration to 6.0 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
interventionNames
1. Drug: Masitinib
2. Other: Best Supportive Care
type
PLACEBO_COMPARATOR
label
Placebo & BSC
description
Placebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
interventionNames
1. Other: Placebo
2. Other: Best Supportive Care

Primary outcomes (1)

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 75 Years

Show eligibility criteria text

Inclusion Criteria:

1. Patient with one of the following documented mastocytosis subtypes (variants): Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis
2. An excess of mast cells or a presence of abnormal mast cells in at least two organs (among skin, bone-marrow and GI Tract).
3. Patient with documented systemic mastocytosis and evaluable disease based upon histological criteria
4. Patient with documented treatment failure of his/her symptom(s) (within the past 2 years) with at least two of the symptomatic treatments used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Antidepressants, Cromoglycate Sodium, Antileukotriene.
5. Patient with severe symptoms of mastocytosis over the 14-day run-in period including at least one among pruritus, flushes, and depression: pruritus score ≥ 9, number of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19.

Exclusion Criteria:

1. Patient with one of the following mastocytosis: Cutaneous 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. Treatment with any investigational agent within 8 weeks prior to screening.

References

Publications (3)

BACKGROUNDPaul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, Grandpeix-Guyodo C, Dubreuil P, Palmerini F, Mansfield CD, Gineste P, Moussy A, Hermine O, Lortholary O. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010 Dec;85(12):921-5. doi: 10.1002/ajh.21894. PMID 21108325
BACKGROUNDLortholary 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, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017 Feb 11;389(10069):612-620. doi: 10.1016/S0140-6736(16)31403-9. Epub 2017 Jan 7. PMID 28069279
DERIVEDLatham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1. PMID 36048877

Registry

Dates and enrollment

Start: Jul 1, 2020
Primary completion: Dec 1, 2024
Completion: Jun 1, 2025
First posted: Apr 3, 2020
Last update posted: May 6, 2023
Enrollment: 140 (estimated)
Lead sponsor: AB Science INDUSTRY
Keywords: 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

Data updated 23 days agoSource updated May 6, 2023source: clinicaltrials

Locations

Locations by country (17)

Country	Sites	Recruiting
France	8	8
Ukraine	2	2
Poland	2	2
Romania	1	1
Russia	1	1