A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia
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)
2 other identifiers
interventional
122
7 countries
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2013
Typical duration for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 18, 2013
CompletedFirst Posted
Study publicly available on registry
January 23, 2013
CompletedStudy Start
First participant enrolled
February 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2016
CompletedJanuary 25, 2017
January 1, 2017
3.3 years
January 18, 2013
January 24, 2017
Conditions
Outcome Measures
Primary Outcomes (3)
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
Secondary Outcomes (18)
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)
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)
- +13 more secondary outcomes
Study Arms (4)
Part 1: RO5503781
EXPERIMENTALParticipants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.
Part 2: RO5503781 + Cytarabine
EXPERIMENTALParticipants 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.
Part3:RO5503781+Cytarabine+Anthracycline
EXPERIMENTALParticipants 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.
Part 4: Optimized RO5503781 + Cytarabine
EXPERIMENTALParticipants 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.
Interventions
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
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
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
Related Publications (1)
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.
PMID: 33302031DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 18, 2013
First Posted
January 23, 2013
Study Start
February 1, 2013
Primary Completion
June 1, 2016
Study Completion
June 1, 2016
Last Updated
January 25, 2017
Record last verified: 2017-01