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

NCT ID: NCT04093570

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 332 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2027-12-31

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).

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Main Extension Study: 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.

Group Type: EXPERIMENTAL

ASTX727

Intervention Type: DRUG

ASTX727 film-coated, immediate-release FDC tablets

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

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.

Group Type: EXPERIMENTAL

ASTX727

Intervention Type: DRUG

ASTX727 film-coated, immediate-release FDC tablets

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

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.

Group Type: EXPERIMENTAL

ASTX727

Intervention Type: DRUG

ASTX727 film-coated, immediate-release FDC tablets

Interventions

ASTX727

ASTX727 film-coated, immediate-release FDC tablets

Intervention Type: DRUG

Other Intervention Names

cedazuridine + decitabine; INQOVI; DEC-C

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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).

3. Participant is able to understand and comply with the study procedures and understands the risks involved in the study.

4. Participant provides legally effective informed consent before undergoing any study-specific procedure.

5. 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.

1. 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.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

3. Adequate organ function defined as follows:

1. 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.

2. Renal: Calculated creatinine clearance ≥60 mL/min.

Exclusion Criterion for the Main Extension Study:

1. 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.

Exclusion Criteria

1. Participants with known or suspected hypersensitivity to decitabine, cedazuridine, or any of the excipients in the ASTX727 tablets.

2. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.

3. 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.

4. Prior gastric surgery for ulcer disease, weight loss, etc, that would impair normal motility or absorption.

5. Second malignancy currently requiring active chemotherapy. To clarify, participants with breast or prostate cancer stable on or responding to endocrine therapy, are eligible.

6. Known history of human immunodeficiency virus or known seropositive for hepatitis C virus or hepatitis B virus.

7. Active uncontrolled gastric or duodenal ulcer.

8. Participants with acute promyelocytic leukemia.

9. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.

10. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Mayo - Rochester

Rochester, Minnesota, United States

Hackensack Medical Center - 06 FE Study

Hackensack, New Jersey, 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

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Baylor Scott White University Medical Center

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

May Cancer Center

San Antonio, Texas, United States

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

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

Complex Oncology Center - Plovdiv - Base II

Plovdiv, , Bulgaria

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

Princess Margaret Cancer Center

Toronto, , Canada

Hôpital Emile Muller

Mulhouse, Grand Est, France

Städtisches Klinikum Braunschweig

Braunschweig, Lower Saxony, Germany

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Schleswig-Holstein, Germany

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

Debrecen, , Hungary

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.

Wroclaw, Lower Silesian Voivodeship, Poland

Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu

Bucharest, , Romania

Institutul Oncologic Prof. Dr. Ion Chiricuta

Cluj-Napoca, , Romania

Summit Clinical Research s.r.o

Bratislava, , Slovakia

Hospital Universitari Arnau de Vilanova

Lleida, , Spain

Clínica Universidad de Navarra - Madrid

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Countries

United States; Armenia; Austria; Bulgaria; Canada; France; Germany; Hungary; Italy; Poland; Romania; Slovakia; Spain

Other Identifiers

2024-516293-29-01

Identifier Type: CTIS

Identifier Source: secondary_id

2018-003942-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ASTX727-06

Identifier Type: -

Identifier Source: org_study_id