A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose)

NCT04093570 | Enrolling By Invitation Phase 2 FDA Drug

• 3 other identifiers: ASTX727-062024-516293-29-012018-003942-18
• Study Type: interventional
• Target: 332
• Locations: 13 countries
• Sites: 48

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.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes

Keywords

cedazuridine; decitabine; MDS; CMML; AML; myelodysplastic syndromes; chronic myelomonocytic leukemia; acute myeloid leukemia; ASTX727; INQOVI

Outcome Measures

Primary Outcomes (22)

• Main Extension Study: Safety: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

  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.

  From date of transition into this extension study until 30 days following the last dose, up to approximately 2 years

• 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-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-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: AUC0-8h: 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: AUC0-8h: 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: 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: AUC0-24h: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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)

• 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)

• 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: 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)

Secondary Outcomes (2)

• 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)

• 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)

Study Arms (3)

Main Extension Study: ASTX727

EXPERIMENTAL

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.

Drug: ASTX727

Substudy Arm A: ASTX727 With High-Calorie/High-Fat Breakfast Meal on Day 4

EXPERIMENTAL

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.

Drug: ASTX727

Substudy Arm B: ASTX727 With Low-Calorie/Low-Fat Breakfast Meal on Day 4

EXPERIMENTAL

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.

Drug: ASTX727

Interventions

ASTX727 DRUG

ASTX727 film-coated, immediate-release FDC tablets

Also known as: cedazuridine + decitabine, INQOVI, DEC-C

Main Extension Study: ASTX727; Substudy Arm A: ASTX727 With High-Calorie/High-Fat Breakfast Meal on Day 4; Substudy Arm B: ASTX727 With Low-Calorie/Low-Fat Breakfast Meal on Day 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previous participation in a Taiho (formerly Astex)-sponsored ASTX727 clinical trial (including, but not limited to studies ASTX727-01, ASTX727-02, and ASTX727-04, , ASTX727-17, and ASTX727-18, and the food effect substudy of ASTX727-06) in which the participant was treated with ASTX727 and was still on active treatment with ASTX727 at the time of study completion as determined by Taiho.
• Participant is considered to be benefitting from ASTX727 treatment in the opinion of the treating investigator at the time of parent study completion (Participants must not be withdrawn from the parent study until eligibility for this study is confirmed).
• Participant is able to understand and comply with the study procedures and understands the risks involved in the study.
• Participant provides legally effective informed consent before undergoing any study-specific procedure.
• Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential must agree to practice 1 highly effective contraceptive methods of birth control during the study and for 6 months after the last dose of study treatment, agree not to donate eggs for the purpose of reproduction during this period and must agree not to become pregnant for 6 months after completing treatment; men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures and must agree not to father a child while receiving ASTX727 and for at least 3 months after completing ASTX727 treatment.
• Participants must have a confirmed diagnosis of-
• i. Myelodysplastic syndromes (MDS) including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia \[CMML\])), and participants with MDS International Prognostic Scoring System (IPSS) int-1, int-2, or high-risk MD.
• ii. Acute myeloid leukemia (AML), as diagnosed according to the 2016 World Health Organization (WHO) guidelines on acute leukemia, of any subtype except M3 (acute promyelocytic leukemia), who are not candidates for intensive chemotherapy, including participants receiving hypomethylating agent (HMA) treatment, who have a confirmed diagnosis and a prior confirmatory bone marrow report. Participants who are currently receiving HMA treatment must complete the ongoing (at the time of Screening) treatment cycle before enrolling in this study; timing of start of treatment cycle with ASTX727 is at the principal investigator's discretion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate organ function defined as follows:
• Hepatic: Total bilirubin ≤1.5 × upper limit of normal (ULN); aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) ≤5 × ULN.
• Renal: Calculated creatinine clearance ≥60 mL/min.
• \. Any participant who, in the opinion of the investigator, may have other conditions, organ dysfunction, or for whom safety data from parent study participation suggests the risks of continuing treatment with ASTX727 may outweigh the benefits.

You may not qualify if:

• Participants with known or suspected hypersensitivity to decitabine, cedazuridine, or any of the excipients in the ASTX727 tablets.
• Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
• Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of decitabine + cedazuridine or compromise the integrity of the study outcomes.
• Prior gastric surgery for ulcer disease, weight loss, etc, that would impair normal motility or absorption.
• Second malignancy currently requiring active chemotherapy. To clarify, participants with breast or prostate cancer stable on or responding to endocrine therapy, are eligible.
• Known history of human immunodeficiency virus or known seropositive for hepatitis C virus or hepatitis B virus.
• Active uncontrolled gastric or duodenal ulcer.
• Participants with acute promyelocytic leukemia.
• Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
• Treated with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant AEs from previous treatment with investigational drug or therapy.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (48)

Compassionate Care Research Group

Fountain Valley, California, 92708, United States

Location

Boca Raton Clinical Research

Plantation, Florida, 33322, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, 21231, United States

Location

Cancer and Hematology Centers for Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Mayo - Rochester

Rochester, Minnesota, 55905, United States

Location

Hackensack Medical Center - 06 FE Study

Hackensack, New Jersey, 07601, United States

Location

Hackensack Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rosewell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Roswell Park Cancer Institute - 06 FE Study

Buffalo, New York, 14263, United States

Location

Gabrail Cancer Center Research - 06 FE Study

Canton, Ohio, 44718, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Oregon Health and Science University

Portland, Oregon, 92739, United States

Location

Charleston Hematology Oncology Associates

Charleston, South Carolina, 29414, United States

Location

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Baylor Scott White University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

May Cancer Center

San Antonio, Texas, 78229, United States

Location

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Erebuni Medical Center

Yerevan, Armenia

Location

Hematology Center After Prof. R. Yeolyan (Adult Blood Disorders)

Yerevan, Armenia

Location

Hematology Center After Prof. R. Yeolyan (Clinic of Adults Oncology)

Yerevan, Armenia

Location

National Center of Oncology Named After V.A. Fanarjyan

Yerevan, Armenia

Location

Wiener Gesundheitsverbund - Klinik Hietzing 06 FE Study

Vienna, 1130, Austria

Location

Wiener Gesundheitsverbund - Klinik Hietzing 06 Study

Vienna, 1130, Austria

Location

Complex Oncology Center - Plovdiv - Base II

Plovdiv, 4000, Bulgaria

Location

Specialized Hospital for Active Treatment of Hematological Disease EAD

Sofia, 1797, Bulgaria

Location

University of Alberta Hospital

Edmonton, T6G 2B7, Canada

Location

QEII Health Sciences Centre

Nova Scotia, B3H 2Y9, Canada

Location

The Ottawa Hosptial

Ottawa, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

Location

Princess Margaret Cancer Center

Toronto, M5G 2M9, Canada

Location

Hôpital Emile Muller

Mulhouse, Grand Est, 68100, France

Location

Städtisches Klinikum Braunschweig

Braunschweig, Lower Saxony, 38114, Germany

Location

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Debreceni Egyetem Klinikai Kozpont, Belgyogyszati Klinika, B epulet, Hematologia

Debrecen, 4032, Hungary

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.

Wroclaw, Lower Silesian Voivodeship, Poland

Location

Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu

Bucharest, 22328, Romania

Location

Institutul Oncologic Prof. Dr. Ion Chiricuta

Cluj-Napoca, 400015, Romania

Location

Summit Clinical Research s.r.o

Bratislava, 83101, Slovakia

Location

Hospital Universitari Arnau de Vilanova

Lleida, Spain

Location

Clínica Universidad de Navarra - Madrid

Madrid, 28027, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 18, 2019
• Study Start: September 30, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BU (2); AR (4); DE (2); PL (1); SL (1); ES (5); RO (2); US (21); FR (1); CA (5); HU (1); IT (1); AU (2)