Phase II Single Arm Open Pilot Study to Demonstrate the Efficacy of Midostaurin in Symptom Improvement and Decrease of Mast Cell Burden in Patients With Indolent or Smoldering Systemic Mastocytosis.
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Symptom Scoring
研究概览
简要总结
Rationale: Patients with indolent or smoldering systemic mastocytosis can have severe disabling symptoms. Almost all patients have fatigue, a compromised quality of life, hampering normal functioning. Because this form of mastocytosis is not considered life-threatening, mast cell eradication has never been applied and patients receive only symptomatic therapy with histamine blockers. Midostaurin, a c-KIT inhibitor has shown activity regarding symptom control and decrease of malignant mast cells in patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia
详细描述
Objective:
Primary: To study in a pilot phase II trial the efficacy of midostaurin administered at an oral dose of 100 mg twice daily in patients with indolent or smoldering systemic mastocytosis on mediator symptom reduction, documented by the Mastocytosis Symptom Assessment Questionnaire, measured at 3 months.
Secondary:
- To study whether symptom improvement persists at 6 months, and whether midostaurin can reduce mast cell infiltration in the skin and bone marrow, documented by decrease of serum tryptase, decrease of urticaria pigmentosa and decrease of bone marrow mast cells.
- To assess safety and tolerability of midostaurin in the above mentioned settings
Study design: Single arm, open label pilot phase II study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic Mastocytosis (SSM) according to the WHO criteria
- •Presence of the D816V c-KIT mutation
- •Serum tryptase > 20 mg/l
- •Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking drugs. Symptoms will be scored by an adapted MSAF (mastocytosis symptom assessment form) with at least:
- •a pre-study score of 4 or more on 3 non-related items,
- •or a pre-study score of 5 or more on 2 non-related items.
- •one item from the scoring list can be replaced by flushes 7 or more per week or anaphylactic attacks 1 or more per week.
- •Age >18 years
- •Willingness to apply optimal contraceptive measures (double barrier method, both men and women) for women below the age of 55, men at all ages; for both: if sexually active.
- •Written informed consent
排除标准
- •Aggressive systemic mastocytosis, mast cell leukemia, or ASM with or without accompanying non-clonal related non-mast cell disorder (SM-ANHMD).
- •Any known other present malignancy, non-melanoma skin cancers excluded
- •History of malignancy within the last 5 years, non-melanoma skin cancers excluded
- •Any serious comorbidity interfering with therapy compliance and follow-up compliance
- •Pregnancy
- •Patients not willing or who are not able to comply with contraceptive measures
研究组 & 干预措施
Midostaurin
Treatment with Midostaurin, twice daily 100 mg orally for 6 months continuously.
干预措施: Midostaurin, (Drug)
结局指标
主要结局
Symptom Scoring
时间窗: 12 weeks
Percent change in the total score ("Sumscore") of all symptoms assessed by the Mastocytosis Symptom Assessment Form (MSAF) after 12 weeks.
次要结局
- Mast cell burden(6 months)
- Persistence of improvements(6 months)
- Adverse events(6 months)
研究者
Prof.dr. J.C. Kluin-Nelemans
Prof.dr.
University Medical Center Groningen