A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy
研究概览
简要总结
The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.
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
- •Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) or accelerated phase (AP)with resistance to at least one prior BCR-ABL targeting TKI
- •Documented chronic phase CML
- •Adequate end organ function
- •Female patients of childbearing potential must have a negative serum pregnancy test and must be using highly effective methods of contraception. Male patients with female partners of child-bearing potential must use condoms.
排除标准
- •Impaired cardiac function
- •Severe and/or uncontrolled concurrent disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
- •History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- •Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to entering the study
- •Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug.
- •Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Nilotinib + LDE225
The planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y
干预措施: Nilotinib + LDE225 (Drug)
结局指标
主要结局
Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy
时间窗: 56 days (2 treatment cycles at 28 days each)
Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225
次要结局
- Complete molecular response (CMR) rates at 3, 6 and 12 months(336 days (12 treatment cycles))
- Major cytogenic response (MCyR) rates by 3, 6 and 12 months(336 days (12 treatment cycles))
- No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms(336 days (12 treatment cycles))
- Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC)(50 days)
- Major molecular response (MMR) rates at 3, 6 and 12 months(336 days (12 treatment cycles))
- Complete cytogenic response (CCyR) rates by 3, 6 and 12 months(336 days (12 treatment cycles))