Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis (AB06006)
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| ClinicalTrials.gov Identifier: NCT00814073 |
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Recruitment Status :
Completed
First Posted : December 23, 2008
Last Update Posted : December 3, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Indolent Systemic Mastocytosis | Drug: Masitinib Drug: Placebo Other: Best Supportive Care | Phase 3 |
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 : | 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 |
|---|---|
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Experimental: Masitinib & BSC
Masitinib (6 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
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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. |
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Placebo Comparator: Placebo & BSC
Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
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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. |
- 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).
- 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)
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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 |
Inclusion Criteria:
- Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis, Severe Indolent Mastocytosis
- 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
- 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
- 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
- Patients with OPA ≥ 2 (moderate to intolerable general handicap)
- ECOG ≤ 2
- Patient with adequate organ function
Exclusion Criteria:
- 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)
- Previous treatment with any Tyrosine Kinase Inhibitor
- 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.
- 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
- Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline
- Treatment with any investigational agent within 4 weeks prior to baseline
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
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| Principal Investigator: | Olivier Lortholary, MD, PhD | Hôpital Necker, Paris, France |
Publications of Results:
Other Publications:
| Responsible Party: | AB Science |
| ClinicalTrials.gov Identifier: | NCT00814073 |
| Other Study ID Numbers: |
AB06006 |
| First Posted: | December 23, 2008 Key Record Dates |
| Last Update Posted: | December 3, 2019 |
| Last Verified: | November 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |
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Mastocytosis Mastocytosis, Systemic Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue |
Neoplasms by Histologic Type Neoplasms Mast Cell Activation Disorders Immune System Diseases |