An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 38
- 主要终点
- For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
研究概览
简要总结
This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in combination with ruxolitinib.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO)
- •Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of ruxolitinib in the 8 weeks prior to study entry
- •Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT
- •Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0
- •ECOG performance status of 0 to 2
排除标准
- •Patients who are positive for TP53 mutations
- •Documented disease progression or clinical deterioration any time while on ruxolitinib treatment
- •Patients who have had a documented spleen response to ruxolitinib.
- •Prior splenectomy
- •Prior MDM2 inhibitor therapy or p53-directed therapy
研究组 & 干预措施
Part A, Arm 1, Cohort 1
KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
干预措施: KRT-232 (Drug)
Part A, Arm 1, Cohort 1
KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
时间窗: 15 months
Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination.
For Phase 2:To determine the spleen volume reduction (SVR) at Week 24
时间窗: 6 months after last patient enrolled
The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan
次要结局
- To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)(43 months)
- To determine spleen response(43 months)