A 3-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate Safety and Efficacy of Avapritinib (BLU-285), a Selective KIT Mutation-Targeted Tyrosine Kinase Inhibitor, in Indolent and Smoldering Systemic Mastocytosis With Symptoms Inadequately Controlled With Standard Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 251
- 试验地点
- 49
- 主要终点
- Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM
研究概览
简要总结
This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •1. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and central review of B- and C-findings by WHO diagnostic criteria.
- •2. Patient must have moderate-to-severe symptoms based on minimum mean total symptom score (TSS) of the ISM Symptom Assessment Form (ISM-SAF) over the 14-day eligibility screening period.
- •3. Patient must have failed to achieve adequate symptom control for 1 or more Baseline symptoms.
- •4. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or equivalent, and the dose must be stable for ≥ 14 days.
- •5. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to
排除标准
- •1. Patient has been diagnosed with any of the following WHO SM subclassifications: cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia, or mast cell sarcoma.
- •2. Patient must not have received prior treatment with avapritinib.
- •3. Patient must not have had any cytoreductive therapy including but not limited to masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of the drug (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy < 28 days or 5 half-lives of the drug (whichever is longer), before beginning the 14-day ISM-SAF eligibility TSS assessment.
- •4. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
- •5. Patient must not have received any hematopoietic growth factor the preceding 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.
- •6. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of > 480 msec.
研究组 & 干预措施
(Part 1) Avapritinib Dose 1 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
干预措施: Avapritinib (Drug)
(Part 1) Avapritinib Dose 2 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
干预措施: Avapritinib (Drug)
(Part 1) Avapritinib Dose 3 + BSC
Avapritinib will be administered orally in continuous 28-day cycles
干预措施: Avapritinib (Drug)
(Part 1) Placebo + BSC
Placebo will be administered orally in continuous 28-day cycles
干预措施: Placebo (Drug)
(Part 2) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
干预措施: Avapritinib (Drug)
(Part 2) Placebo + BSC
Placebo will be administered orally in continuous 28-day cycles
干预措施: Placebo (Drug)
(Part 3) Avapritinib RP2D + BSC
Avapritinib will be administered orally in continuous 28-day cycles
干预措施: Avapritinib (Drug)
结局指标
主要结局
Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM
时间窗: 9 months
Part 3: Number of Participants with Adverse Events
时间窗: Up to 5 years
Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) as compared to placebo
时间窗: 6 months
0 - 110 points (higher value represents worse symptom outcomes)
次要结局
- Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline(6 months)
- Part 2: Proportion of patients with a ≥50% reduction in serum tryptase(6 months)
- Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline(6 months)
- Parts 1, 2, and 3: Change in best supportive care (BSC) concomitant medication usage(Up to 5 years)
- Parts 1, 2, and 3: Change in Patient's Global Impression of Symptom Severity (PGIS)(Up to 5 years)
- Part 2: Proportion of patients with ≥30% reduction in ISM-SAF TSS(6 months)
- Parts 1, 2, and 3: Change in bone marrow mast cells(Up to 5 years)
- Parts 1, 2, and 3: Change from Baseline in ISM-SAF Score(Up to 5 years)
- Parts 1, 2, and 3: Change in Patients' Global Impression of Change (PGIC)(Up to 5 years)
- Parts 1, 2, and 3: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L)(Up to 5 years)
- Part 2: Proportion of patients with ≥50% reduction in ISM-SAF TSS(6 months)
- Parts 1, 2, and 3: Change in serum tryptase(Up to 5 years)
- Parts 1, 2, and 3: Change in KIT D816V allele burden in blood(Up to 5 years)
- Parts 1, 2, and 3: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)(Up to 5 years)
- Parts 1, 2, and 3: Change in 12-item Short Form Health Survey (SF-12)(Up to 5 years)
- Parts 1, 2, and 3: Safety of avapritinib as assessed by number of adverse events(Up to 5 years)