A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose)
- Conditions
- Acute Myeloid LeukemiaMyelodysplastic SyndromesChronic Myelomonocytic Leukemia
- Interventions
- Registration Number
- NCT04093570
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief Summary
Extension study to provide ongoing long-term treatment with ASTX727 for participants who were benefitting from ASTX727 treatment in a previous Taiho (formerly Astex)-sponsored clinical study of ASTX727 (including, but not limited to ASTX727-01 \[NCT02103478\], ASTX727-02 \[NCT03306264\], ASTX727-04 \[NCT03813186\]), ASTX727-06 \[NCT04093570\] food effect substudy, ASTX727-17 \[NCT04953897\], and ASTX727-18 \[NCT04953910\] to obtain long-term safety information.
The purpose of the Food Effect Substudy was to evaluate the pharmacokinetics (PK) and safety of decitabine and cedazuridine when ASTX727 was given under fed (high-calorie/high-fat meal or low-calorie/low-fat meal) versus fasted conditions. Food Effect Substudy has now completed.
- Detailed Description
Main Extension Study: Participants will attend clinic visits on Day 1 of each 28-day cycle to undergo study procedures and to be given ASTX727 tablets for Days 1-5 of that dose cycle. Participants should continue to receive the same ASTX727 dose and regimen they were receiving in the last cycle of the parent study in which they were originally enrolled. Subsequent treatment delays and/or dose reductions are at the discretion of the investigator as guided by the dose adjustment guidelines of the parent study protocol.
Food Effect Substudy: Participants received ASTX727 once daily on Days 1 through 5 followed by a 23-day treatment-free period in a 28-day cycle (Cycle 1). Participants received either a high-calorie, high-fat breakfast meal (Arm A) or a low-calorie/low-fat breakfast meal (Arm B) predose on Day 4. Participants in Arms A and B received ASTX727 on Days 1, 2, 3, and 5 in the fasted condition. Participants may continue treatment with ASTX727 in Cycle 2 onwards in the ASTX727-06 study at the Investigator's discretion, where they continued to receive ASTX727. This substudy consists of a 21-day Screening Period, a 1-cycle (28 days) Treatment Period, and a 30-day (+7 days) Safety Follow-up Period (only if the participant discontinues from the ASTX727-06 food effect substudy and does not continue to receive ASTX727 in the ASTX727-06 study).
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 332
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Substudy Arm B: ASTX727 With Low-Calorie/Low-Fat Breakfast Meal on Day 4 ASTX727 Participants received ASTX727 once daily on Days 1 through 5 in a 28-day cycle (Cycle 1). Participants fasted for at least 2 hours before and 2 hours after dosing on Days 1, 3, 5 and for at least 10 hours before and 4 hours after dosing on Day 2. Participants received low-calorie/low-fat breakfast meal after an overnight fast of at least 10 hours before dosing on Day 4 and will continue to fast for at least 4 hours post-dose. Participants continued treatment with ASTX727 in Cycle 2 onwards in the ASTX727-06 study at the Investigator's discretion, where they continued to receive ASTX727 unless there was occurrence of disease progression requiring alternative therapy, unacceptable toxicity, noncompliance, a decision to discontinue treatment, or if the participant withdraws from the study. Main Extension Study: ASTX727 ASTX727 The recommended starting dose is the fixed-dose combination (FDC) standard dose (SD) tablet, containing 100 mg cedazuridine and 35 mg decitabine, once daily, Days 1 through 5 in 28-day cycles. Participants should receive ASTX727 at the same dose they received in the last cycle of their parent study; if an adjustment from that dose is required, a different total cycle dose may be employed, as guided by the dose adjustment guidelines in the parent study protocol. Substudy Arm A: ASTX727 With High-Calorie/High-Fat Breakfast Meal on Day 4 ASTX727 Participants received ASTX727 once daily on Days 1 through 5 in a 28-day cycle (Cycle 1). Participants fasted for at least 2 hours before and 2 hours after dosing on Days 1, 3, 5 and for at least 10 hours before and 4 hours after dosing on Day 2. Participants received a high-calorie/high-fat breakfast meal after an overnight fast of at least 10 hours before dosing on Day 4 and continued to fast for at least 4 hours post-dose. Participants continued treatment with ASTX727 in Cycle 2 onwards in the ASTX727-06 study at the Investigator's discretion, where they continued to receive ASTX727 unless there was occurrence of disease progression requiring alternative therapy, unacceptable toxicity, noncompliance, a decision to discontinue treatment, or if the participant withdraws from the study.
- Primary Outcome Measures
Name Time Method Food Effect Substudy: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to Last Concentration Measured of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 ( up to 28 days) Food Effect Substudy: AUC0-8h: Area Under the Concentration-time Curve From Time Zero to 8 Hours of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC0-24h: Area Under the Concentration-time Curve From Time Zero to 24 Hours of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to Last Concentration Measured of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC0-24h: Area Under the Concentration-time Curve From Time Zero to 24 Hours of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC 0-inf: Area Under the Concentration-time Curve From Time Zero to Infinity of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: Cmax: Maximum Observed Plasma Concentration of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: Tmax: Time of First Occurrence of Cmax of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: Tmax: Time of First Occurrence of Cmax of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Main Extension Study: Safety: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) From date of transition into this extension study until 30 days following the last dose, up to approximately 2 years An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAEs are defined as events that first occur or worsen on or after the date of the first study treatment until 30 days after the last dose of study treatment, or the start of an alternative anticancer treatment, whichever first.
Food Effect Substudy: AUC0-8h: Area Under the Concentration-time Curve From Time Zero to 8 Hours of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC 0-inf: Area Under the Concentration-time Curve From Time Zero to Infinity of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: Tmax: Time of First Occurrence of Cmax of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: T1/2: Terminal Half Life of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC 0-inf: Area Under the Concentration-time Curve From Time Zero to Infinity of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: Cmax: Maximum Observed Plasma Concentration of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: T1/2: Terminal Half Life of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to Last Concentration Measured of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC0-8h: Area Under the Concentration-time Curve From Time Zero to 8 Hours of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: AUC0-24h: Area Under the Concentration-time Curve From Time Zero to 24 Hours of Cedazuridine-epimer in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: Cmax: Maximum Observed Plasma Concentration of Cedazuridine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days) Food Effect Substudy: T1/2: Terminal Half Life of Decitabine in the Fasted and Fed State Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post dose on Days 2 (fasted state) and 4 (fed state) in Cycle 1 (up to 28 days)
- Secondary Outcome Measures
Name Time Method Food Effect Substudy: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs), by Severity From first dose of study drug up to 30 days after the last dose (Up to approximately 65 days) An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAEs are defined as events that first occur or worsen on or after the date of the first study treatment (Cycle 1 Day 1) until 30 days after the last dose of study treatment, or the start of an alternative anticancer treatment, whichever first. Severity of TEAEs were graded using Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03).
Food Effect Substudy: Percentage of Participants with Clinically Significant Abnormal Laboratory Values From Day 1 up to Day 28 in Cycle 1 (Up to 28 days) The laboratory parameters of hematology, serum chemistry, and urinalysis were assessed.
Trial Locations
- Locations (48)
Complex Oncology Center - Plovdiv - Base II
🇧🇬Plovdiv, Bulgaria
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
Mayo - Rochester
🇺🇸Rochester, Minnesota, United States
Hackensack Medical Center - 06 FE Study
🇺🇸Hackensack, New Jersey, United States
Princess Margaret Cancer Center
🇨🇦Toronto, Canada
HĂ´pital Emile Muller
🇫🇷Mulhouse, Grand Est, France
Städtisches Klinikum Braunschweig
🇩🇪Braunschweig, Niedersachsen, Germany
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
🇩🇪Lübeck, Schleswig-Holstein, Germany
ClĂnica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Institutul Oncologic Prof. Dr. Ion Chiricuta
🇷🇴Cluj-Napoca, Romania
Summit Clinical Research s.r.o
🇸🇰Bratislava, Slovakia
Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.
🇵🇱Wroclaw, Dolnoslaskie, Poland
Compassionate Care Research Group
🇺🇸Fountain Valley, California, United States
Boca Raton Clinical Research
🇺🇸Plantation, Florida, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
🇺🇸Baltimore, Maryland, United States
Cancer and Hematology Centers for Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Hackensack Medical Center
🇺🇸Hackensack, New Jersey, United States
Rosewell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Roswell Park Cancer Institute - 06 FE Study
🇺🇸Buffalo, New York, United States
Gabrail Cancer Center Research - 06 FE Study
🇺🇸Canton, Ohio, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
Baylor Scott White University Medical Center
🇺🇸Dallas, Texas, United States
Vanderbilt - Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
May Cancer Center
🇺🇸San Antonio, Texas, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu
🇷🇴Bucharest, Romania
Erebuni Medical Center
🇦🇲Yerevan, Armenia
Hematology Center After Prof. R. Yeolyan (Adult Blood Disorders)
🇦🇲Yerevan, Armenia
Hematology Center After Prof. R. Yeolyan (Clinic of Adults Oncology)
🇦🇲Yerevan, Armenia
National Center of Oncology Named After V.A. Fanarjyan
🇦🇲Yerevan, Armenia
Wiener Gesundheitsverbund - Klinik Hietzing 06 FE Study
🇦🇹Vienna, Austria
Wiener Gesundheitsverbund - Klinik Hietzing 06 Study
🇦🇹Vienna, Austria
Specialized Hospital for Active Treatment of Hematological Disease EAD
🇧🇬Sofia, Bulgaria
University of Alberta Hospital
🇨🇦Edmonton, Canada
QEII Health Sciences Centre
🇨🇦Nova Scotia, Canada
The Ottawa Hosptial
🇨🇦Ottawa, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Canada
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Debreceni Egyetem Klinikai Kozpont, Belgyogyszati Klinika, B epulet, Hematologia
đź‡đź‡şDebrecen, Hungary
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Hospital ClĂnico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario La Fe
🇪🇸Valencia, Spain