NCT03922100终止1 期
A Phase I/II Study of NMS-03592088, a FLT3, KIT and CSF1R Inhibitor, in Patients With Relapsed or Refractory AML or CMML
Nerviano Medical Sciences11 个研究点 分布在 3 个国家目标入组 63 人开始时间: 2019年4月3日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 63
- 试验地点
- 11
- 主要终点
- Phase I - Number of Participants With Drug Related First-cycle Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to explore safety, tolerability, including the maximum tolerated dose and the recommended Phase II dose (RP2D), and antitumor activity of NMS-03592088 in adult patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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 relapsed/refractory disease who have failed standard therapy or are unsuitable for standard treatment, with one the following confirmed diagnosis: AML as defined by the European LeukemiaNet (ELN)
- •Patients with confirmed diagnosis of AML as defined by the 2022 ELN recommendations
- •Patients must have failed standard of care.
- •Adult (age ≥ 18 years) patients
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •The interval from prior antitumor treatment to time of NMS-03592088 administration should be at least 2 weeks for any agents other than hydroxyurea.
- •All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade ≤1
- •Adequate hepatic and renal function
- •Patients must use highly effective contraception.
- •Signed and dated IEC or IRB-approved informed consent form.
排除标准
- •Current enrollment in another interventional clinical study
- •Diagnosis of acute promyelocytic leukemia or Breakpoint cluster region-Abelson (BCR-ABL)-positive leukaemia
- •Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
- •Patients with known leukemia involvement of central nervous system (CNS)
- •Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non-hematologic toxicities of Grade ≥2 related to the transplant
- •Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
- •Patients with QTcF interval ≥ 480 milliseconds or with risk factors for torsade de pointes
- •Pregnancy.
- •Breast-feeding or planning to breast feed during the study or within 3 months after study treatment.
- •Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
- •Known active, life threatening or clinically significant uncontrolled systemic infection.
- •Known active gastrointestinal disease
- •Known active gastrointestinal ulcer
- •Other severe or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
- •Known diagnosis of myasthenia gravis
- •Signs or symptoms of myasthenia gravis or stroke during screening
- •Patients with myasthenia gravis specific autoantibodies or any known history of myasthenia gravis (MG) autoantibodies at screening window
- •Concomitant medications with the potential to cause de novo myasthenia gravis, worsening of myasthenia gravis or cause myasthenia gravis-like symptoms
- •Uncontrolled hypertension, atrial fibrillation or flutter, ventricular arrhythmia or receiving treatment for cardiac rhythm disorder or diabetes that is not adequately controlled
- •Other protocol specific inclusion/exclusion criteria may apply
研究组 & 干预措施
NMS-03592088
Experimental
Phase I Dose Escalation
- Schedule A - Starting dose of 20 mg/day
- Schedule B - Starting dose of 120 mg/day
Only one dose level open for enrollment except EU backfill cohorts.
Phase II Dose Expansion (Exploratory) - (EU)
Recommended Phase II Dose (RP2D) of NMS-03592088 in Phase 1
- Cohort 1: Patients who have failed standard of care including venetoclax and gilteritinib based therapies
- Cohort 2: Patients who have failed standard of care
干预措施: NMS-03592088 (Drug)
结局指标
主要结局
Phase I - Number of Participants With Drug Related First-cycle Dose Limiting Toxicities (DLTs)
时间窗: From screening to end of first 28-days cycle (47 months)
DLTs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Phase II - Number of Participants Who Achieved Composite Complete Remission (CRc) Rate i.e. Complete Remission (CR) + Complete Remission With Incomplete Hematologic Recovery (CRi).
时间窗: At Screening; Day 1 of Cycle 2 and Cycle 3; and Day 1 at subsequent even cycle; up to End of Treatment visit (within 7 days of the final dose of study drug), up to 17 months
CR = complete remission; CRc = composite complete remission rate; CRh = complete remission with partial hematologic recovery, CRi = complete remission with incomplete hematologic recovery; MLFS = morphologic leukemia free state; ORR = overall response rate; SD = stable disease Categories defined by the 2022 European LeukemiaNet (ELN) recommendations.
次要结局
- Treatment-emergent Adverse Events (TEAEs) Graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5.0 Criteria(Adverse events were collected from screening visit and assessed up to 18 months)
- Pharmacokinetic Parameters: Maximum Plasma Concentration (Cmax), Last Measurable Concentration (Clast), and Average Concentration (Cavg) of NMS-03592088(Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28)
- Pharmacokinetic Parameters: Time to Maximum Plasma Concentration (Tmax), Time to Last Measurable Concentration (Tlast), and Terminal Elimination Half-life (t½,z) of NMS-03592088(Schedule A: Day 1 and 21 Schedule B: Day 1 and 28)
- Pharmacokinetic Parameter: Area Under the Concentration-time Curve to the Last Measurable Concentration (AUClast) and Area Under the Concentration-time Curve From Time Zero to 24 Hour (AUC0-24) of NMS-03592088(Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28)
- Pharmacokinetic Parameters: Apparent Volume of Distribution (V/F) and Apparent Volume of Distribution at Steady State (Vss/F)(Schedule A: Day 21)
- Pharmacokinetic Parameters: Apparent Plasma Clearance (CL/F) and Apparent Plasma Clearance at Steady State (CLss/F)(Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28 CL/F: Evaluation of CL/F for Day 1 of all arms in Schedule A and Schedule B and Day 28 of Schedule B has not been performed)
- Pharmacokinetic Parameters: Accumulation Ratios (RA) for AUC0-24 and Cmax(Schedule A: Day 21 Schedule B: Day 28 Evaluation of Accumulation ratios (RA) for AUC0-24 and Cmax on Day 1 of all arms in Schedule A and Schedule B has not been performed.)
- Pharmacokinetic Parameters: Fraction Excreted Unchanged (FE) of NMS-03592088(Schedule A: Day 21 Schedule B: Day 28 Evaluation of Fraction excreted unchanged (FE) for Arms 20, 40, 80, 120 and 180 mg of Schedule A and Arm 360+150 mg of Schedule B has not been performed.)
- Rate of Participants Bridged To Hemopoietic Stem Cell Transplantation(From the date of first response up to end of study (approximately 1.5 years))
- Best Response Rate for Participants With Acute Myeloblastic Leukemia (AML).(From the date of treatment initiation up to end of study (approximately 1.5 years))
- For AML and in Phase II Only: Number of Participants Who Achieved Complete Remission (CR)(From the date of first response up to end of study (approximately 1.5 years))
- For AML and in Phase II Only: Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate(From the date of first response up to end of study (approximately 1.5 years))
- For AML and in Phase II Only: Overall Response Rate (ORR: CRc + CRh + MLFS + PR)(From the date of first response up to end of study (approximately 1.5 years))
研究者
研究点 (11)
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