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)
Sponsor study identifier
Secondary identifiers
EUDRACT_NUMBER
interventional
122
7 countries
12
Study Start
February 2013
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
June 2016
Actual (reported)Study Completion
June 2016
Actual (reported)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.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
June 2016
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
January 18, 2013
Actual (reported)January 23, 2013
Actual (reported)February 2013
Date type not reportedThis date has not been verified as actual or estimated.
June 2016
Actual (reported)June 2016
Actual (reported)Maximum Tolerated Dose (MTD) and/ or Recommended Phase 2 Dose (RP2D) of RO5503781
Day 1 up to Day 42
Proportion of Participants with Dose-Limiting Toxicities (DLTs)
Day 1 up to Day 42
Safety: Proportion of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline up to approximately 2 years
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) (in Micrograms per Milliliters [mcg/mL]) of RO5503781, Cytarabine,1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
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
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
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
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)
Participants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.
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.
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
USC Norris Cancer Center
Los Angeles, California, 90033, United States
New York Medical College
Valhalla, New York, 10595, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Cancer Therapy & Research Ctr; Dept Institute for Drug Development
San Antonio, Texas, 78229, United States
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000, Australia
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, M5G 2M9, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Yee K, Papayannidis C, Vey N, Dickinson MJ, Kelly KR, Assouline S, Kasner M, Seiter K, Drummond MW, Yoon SS, Lee JH, Blotner S, Jukofsky L, Pierceall WE, Zhi J, Simon S, Higgins B, Nichols G, Monnet A, Muehlbauer S, Ott M, Chen LC, Martinelli G. Murine double minute 2 inhibition alone or with cytarabine in acute myeloid leukemia: Results from an idasanutlin phase 1/1b study small star, filled. Leuk Res. 2021 Jan;100:106489. doi: 10.1016/j.leukres.2020.106489. Epub 2020 Dec 1.
Clinical Trials
Hoffmann-La Roche
122 participants (actual enrollment reported by the registry).
First Submitted
January 18, 2013
First Posted
January 23, 2013
Study Start
February 2013
Date type not reportedThis date has not been verified as actual or estimated.
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
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)
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.
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.
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.
Idarubicin will be administered as per standard clinical practice.
Daunorubicin will be administered as per standard clinical practice.
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.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Contact the study team to confirm eligibility.
Montreal, Quebec, H3T 1E2, Canada
Institut J Paoli I Calmettes; Onco Hematologie 2
Marseille, 13273, France
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh
Bologna, Emilia-Romagna, 40138, Italy
Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
Glasgow, G12 0YN, United Kingdom
Primary Completion
June 2016
Actual (reported)Study Completion
June 2016
Actual (reported)Last Updated
January 25, 2017
Record last verified: 2017-01
Download the complete ClinicalTrials.gov record imported by Syfrah, including fields not shown in this page. The registry may contain a newer revision.
Source: ClinicalTrials.gov.
JSON downloads include source attribution and retrieval details alongside the unchanged original record or the separately normalized values.
Source retrieved: