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A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia

2017年1月24日 更新者：Hoffmann-La Roche

A Multi-Center, Open-Label, Phase 1/1b Study of Escalating Doses of RO5503781 Administered Orally as 1) a Single Agent, 2) In Combination With Cytarabine, or 3) With Cytarabine and Anthracycline and 4) Assessing PK and Safety of New Optimized Formulation of RO5503781 With Cytarabine in Patients With Acute Myelogenous Leukemia (AML)

This Phase 1/1b, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia. In Part 1, RO5503781 will be administered in escalating doses as a single agent, and in Part 2, RO5503781 will be administered in combination with cytarabine. An optional Part 3 in which RO5503781 will be administered with cytarabine and anthracycline may be considered . In Part 4, the safety and pharmacokinetic profile of an optimized formulation of RO5503781 in combination with cytarabine will be assessed.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

122

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 加拿大
    • Ontario
      • Toronto、Ontario、加拿大、M5G 2M9
        • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
    • Quebec
      • Montreal、Quebec、加拿大、H3T 1E2
        • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
  • 大韩民国
      • Seoul、大韩民国、03080
        • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
      • Seoul、大韩民国、05505
        • Asan Medical Center
  • 意大利
    • Emilia-Romagna
      • Bologna、Emilia-Romagna、意大利、40138
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh
  • 法国
      • Marseille、法国、13273
        • Institut J Paoli I Calmettes; Onco Hematologie 2
  • 澳大利亚
    • Victoria
      • Melbourne、Victoria、澳大利亚、3000
        • Peter MacCallum Cancer Centre
  • 美国
    • California
      • Los Angeles、California、美国、90033
        • USC Norris Cancer Center
    • New York
      • Valhalla、New York、美国、10595
        • New York Medical College
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19107
        • Thomas Jefferson University
    • Texas
      • San Antonio、Texas、美国、78229
        • Cancer Therapy & Research Ctr; Dept Institute for Drug Development
  • 英国
      • Glasgow、英国、G12 0YN
        • The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Documented/confirmed acute myelogenous leukemia (AML), except for acute promyelocytic leukemia
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 in Part 1 and Part 2, participants enrolled in the extension/tail portion, Part 3 and Part 4 must have an ECOG performance status of 0 or 1
  • All non-hematological adverse events of any prior chemotherapy, surgery or radiotherapy must have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade less than or equal to (</=) 2 prior to starting therapy
  • Adequate hepatic and renal function
  • Willing to submit the blood sampling and bone marrow sampling required by protocol

Additional inclusion criteria for Parts 1-4 may apply.

Exclusion Criteria:

  • Participants receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug, with the exception of hydroxyurea as defined in protocol
  • History of allergic or toxic reactions attributed to cytarabine (Part 2) or history of allergic reactions to components of the formulated product
  • Current evidence of central nervous system (CNS) leukemia
  • Participants with severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Participants with evidence of electrolyte imbalance greater than or equal to (>/=) Grade 2 which cannot be corrected prior to study initiation
  • Pregnant or breastfeeding women
  • Human immunodeficiency virus (HIV) - positive participants receiving anti-retroviral therapy
  • Participants who refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Additional exclusion criteria for Parts 1-4 may apply.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Part 1: RO5503781
Participants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.
药品：RO5503781 MBP
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
实验性的：Part 2: RO5503781 + Cytarabine
Participants will receive RO5503781 in escalating doses on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.
药品：RO5503781 MBP
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
药品：Cytarabine
Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m^2 IV infusion daily.
实验性的：Part3:RO5503781+Cytarabine+Anthracycline
Participants will receive RO5503781 on Days 1 to 5, cytarabine on Days 1 to 7, and anthracycline (daunorubicin or idarubicin) on Days 1 to 3 of each 28-day cycle until disease progression or unacceptable toxicity.
药品：RO5503781 MBP
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
药品：Cytarabine
Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m^2 IV infusion daily.
药品：Idarubicin
Idarubicin will be administered as per standard clinical practice.
药品：Daunorubicin
Daunorubicin will be administered as per standard clinical practice.
实验性的：Part 4: Optimized RO5503781 + Cytarabine
Participants will receive optimized RO5503781 formulation on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.
药品：Cytarabine
Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m^2 IV infusion daily.
药品：RO5503781 SDP
Participants will receive RO5503781 tablets daily (new optimized formulation) containing spray-dried powder (SDP) at recommended dose(s) for development from Phase 1b to Phase 3.

研究衡量的是什么？

主要结果指标

结果测量
大体时间
Maximum Tolerated Dose (MTD) and/ or Recommended Phase 2 Dose (RP2D) of RO5503781
大体时间：Day 1 up to Day 42
Day 1 up to Day 42
Proportion of Participants with Dose-Limiting Toxicities (DLTs)
大体时间：Day 1 up to Day 42
Day 1 up to Day 42
Safety: Proportion of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
大体时间：Baseline up to approximately 2 years
Baseline up to approximately 2 years

次要结果测量

结果测量
措施说明
大体时间
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) (in Micrograms per Milliliters [mcg/mL]) of RO5503781, Cytarabine,1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cycle (Cy) 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cycle (Cy) 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Time to Reach Maximum Plasma Concentrations (Tmax) in hours of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description).
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description).
Pharmacokinetics: Terminal Half-Life (t1/2) (in hours) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Area Under Plasma Concentration-Time Curve Over One Dosing Internal (AUCtau) (in mcg*hour/mL) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Area Under Plasma Concentration-Time Curve From 0 to the Last Measurable Concentration (AUClast) (in mcg*hour/mL) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Area Under Plasma Concentration-Time Curve From 0 to Infinity (AUCinf) (in mcg*hour/mL) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Apparent Oral Clearance (CL/F) (in liters/hour) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Apparent Volume of Distribution (V/F) (in liters) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Apparent Elimination Rate Constant (kel) (in 1/hour) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
大体时间：Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacodynamics: Macrophage Inhibitory Cytokine-1 (MIC1) Serum Levels
大体时间：Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days)
Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days)
Pharmacodynamics: Proportion of Participants With Tumor Suppressor Protein 53 (p53) Mutation, as Assessed by Gene Sequencing and/or Research-Use AmpliChip p53 Test
大体时间：Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Pharmacodynamics: Murine Double Minute-2 (MDM2) Messenger Ribonucleic Acid (mRNA) Expression, as Assessed by Quantitative Real Time Polymerase Chain Reaction (RT-PCR)
大体时间：Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Proportion of Participants With Complete Remission (CR) as best response during study and follow up period, as Assessed Using Bone Marrow and Hematological Examinations
大体时间：Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CR from occurrence of CR to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CR from occurrence of CR to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Complete Remission Without Platelet Recovery (CRp) as best response during study and follow up period as Assessed Using Bone Marrow and Hematological Examinations
大体时间：Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRp from occurrence of CRp to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRp from occurrence of CRp to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Complete Remission With Insufficient Recovery of Peripheral Counts (CRi) or Morphologic Leukemia Free State (MLFS) as Best Response During Study and Follow Up as Assessed Using Bone Marrow and Hematological Examinations
大体时间：Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRi from occurrence of CRi to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRi from occurrence of CRi to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Partial Response (PR) as Best Response During Study and Follow Up Period, as Assessed Using Bone Marrow and Hematological Examinations
大体时间：Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with PR from occurrence of PR to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with PR from occurrence of PR to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Hematologic Improvement (SD/HI) as Best Response During Study and Follow Up Period, as Assessed Using Bone Marrow and Hematological Examinations
大体时间：Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2months for participants with SD/HI from occurrence of SD/HI to 1 year (overall up to approximately 3.25years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2months for participants with SD/HI from occurrence of SD/HI to 1 year (overall up to approximately 3.25years)
Proportion of Participants With Disease Progression as Best Response During Study and Follow Up Period
大体时间：Baseline up to approximately 3.25 years
Baseline up to approximately 3.25 years

合作者和调查者

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Hoffmann-La Roche

出版物和有用的链接

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研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2013年2月1日

初级完成 (实际的)

2016年6月1日

研究完成 (实际的)

2016年6月1日

研究注册日期

首次提交

2013年1月18日

首先提交符合 QC 标准的

2013年1月18日

首次发布 (估计)

2013年1月23日

研究记录更新

最后更新发布 (估计)

2017年1月25日

上次提交的符合 QC 标准的更新

2017年1月24日

最后验证

2017年1月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • NP28679
  • 2012-004882-41 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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