NCT02335814终止1 期
Phase 1/1b, First-in-Human, Dose-Escalation and Expansion Study of FLX925 Administered Orally to Subjects With Relapsed or Refractory Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 51
- 试验地点
- 11
- 主要终点
- Safety: Incidence of adverse events
研究概览
简要总结
This first-in-human (FIH) clinical trial is a Phase 1/1b, open-label, sequential-group, dose-escalation and cohort expansion study evaluating the safety, PK, PD, and antitumor activity of FLX925 in subjects with relapsed or refractory AML.
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
- •Males and females age ≥ 18 yrs;
- •Subjects with histologically confirmed relapsed or treatment refractory AML with the exception of subjects who are in first relapse following a remission >12 months in duration and are eligible for standard therapies (e.g., chemotherapy or stem cell transplantation).
- •Assessment of FLT3 mutation status;
- •Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts:
- •Cohort A: Subjects with a FLT3 mutation (e.g. ITD or D835) with prior FLT3 inhibitor treatment
- •Cohort B: Subjects with a FLT3 mutation (e.g. ITD or D835) without prior FLT3 inhibitor treatment
- •Cohort C: Subjects without a FLT3 mutation at the time of enrollment
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
- •Considered by the investigator to be an appropriate candidate for a Phase 1 clinical study;
- •The interval from prior treatment to time of initiation of FLX925 administration will be ≥ 2 weeks for cytotoxic agents and ≥ 5 half-lives for investigational/non-cytotoxic agents. For patients with rapidly proliferative disease, use of hydroxyurea is allowed if started prior to initiation of study therapy;
- •Clinically significant toxic effects of any prior antitumor therapy (except hydroxyurea) resolved to Grade ≤ 1 before the start of study therapy (bone marrow parameters [Grade 1 to 4 permitted]);
- •Serum AST and ALT ≤ 3 x ULN;
- •Serum bilirubin ≤ 2 x ULN unless due to Gilbert's syndrome or hemolysis or considered to be related to leukemia;
- •Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCl) of ≥ 60 mL/hour by the Cockroft-Gault equation;
- •Normal coagulation profile as evidenced by PT and aPTT ≤ 1.5 x ULN;
- •For women of childbearing potential, negative serum pregnancy test;
- •Women of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study and for 30 days following the last dose;
- •Ability to swallow tablets without difficulty;
- •Willingness to comply with scheduled visits, drug administration plan, protocol-specified bone marrow biopsies;
- •Written informed consent must be provided.
排除标准
- •Subjects with AML in their first relapse following a remission >12 months in duration who are eligible for standard therapies (e.g. chemotherapy or stem cell transplantation);
- •Absolute leukemic blast count in peripheral blood >50,000/ microliter;
- •Active, symptomatic central nervous system (CNS) leukemia;
- •History of another malignancy except for the following: adequately treated local non-melanoma skin cancer; in situ cervical carcinoma; adequately treated, papillary, non-invasive bladder cancer; asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥ 1 year prior to start of study therapy; other adequately treated Stage 1 or 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years.
- •Clinically significant cardiovascular disease;
- •Significant screening electrocardiogram (ECG) abnormalities;
- •Significant risk for bleeding due to active peptic ulcer disease or bleeding diathesis or requirement for systemic anticoagulation or history of significant gastrointestinal, urological, intracranial or other significant bleeding within 1 year from the start of treatment;
- •Significant active gastrointestinal disease that might impair absorption of study therapy;
- •Evidence of an ongoing, uncontrolled systemic infection or an uncontrolled local infection requiring therapy at the time of start of study therapy
- •Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive;
- •Patients known to be positive for hepatitis B or to have active hepatitis C infection;
- •Any evidence of ongoing graft-versus-host disease (GVHD) in subjects with prior progenitor cell transplantation;
- •Pregnancy or breastfeeding;
- •Major surgery within 4 weeks before the start of study therapy;
- •Ongoing immunosuppressive therapy within 14 days prior to the start of study therapy;
- •Subjects currently receiving treatment with any medications that have the following potential properties and who cannot be either discontinued or switched to a different medication:
- •the potential to prolong the QT interval, or
- •strong CYP3A4 inhibitors, or
- •CYP3A4 or CYP2C19 or P glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrates having a narrow therapeutic index;
- •Concurrent participation in another therapeutic clinical trial;
- •Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial.
研究组 & 干预措施
FLX925
Experimental
干预措施: FLX925 (Drug)
结局指标
主要结局
Safety: Incidence of adverse events
时间窗: 30 Months
Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of FLX925
时间窗: 12 Months
Assess the antitumor activity of FLX925 when administered at the RP2D dose
时间窗: 30 Months
次要结局
- Explore the relationships of PK and PD parameters to clinical drug activity as defined by clinical disease response assessments per Cheson criteria(30 Months)
- Evaluate the PK profile of FLX925 (maximum concentration (Cmax), time of the maximum measured concentration (Tmax), area under the concentration-time curve (AUC), and terminal elimination half-life (t1/2)(30 Months)
- Assess the effects of FLX925 on pharmacodynamic (PD) markers (changes in FLT3-ITD and FLT3-D835 allelic burden)(30 Months)
- Characterize tumor control according to clinical disease response assessments per Cheson criteria in subjects receiving FLX925(30 Months)
研究者
研究点 (11)
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