Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS

NCT ID: NCT03502668

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-27

Study Completion Date

2026-01-31

Brief Summary

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Multicenter, open-label study of various ASTX727 LD doses and schedules to assess safety, pharmacodynamics, pharmacokinetics, and hematologic response in subjects with International Prognostic Scoring System (IPSS) risk category of low-risk or Intermediate-1 MDS. This study will be conducted in two phases. In phase 1 subjects will be randomized into 3 cohorts in a 28-day cycles. Phase 2, 80 new subjects will be randomized in a 1:1 ratio into 2 doses/schedules.

Detailed Description

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A Phase 1-2, multicenter, open-label study of various ASTX727 LD doses and schedules to assess the safety, pharmacodynamics (PD), pharmacokinetics (PK), and hematologic response in subjects with IPSS risk category of low-risk or Intermediate-1 MDS. The study will be conducted in 2 phases.

Phase 1: In Stage A, subjects will be randomized into 3 cohorts of 6 subjects each testing different doses of oral decitabine with cedazuridine in 28-day cycles. When safety has been established in Phase 1 Stage A, Phase 1 Stage B will open, wherein additional 30 subjects will be randomized in a 1:1:1 ratio into 3 cohorts of 10 subjects.

Phase 2: Using 2 doses/schedules one of which will be selected from Phase 1, 40 additional subjects per dose/schedule will be randomized in a 1:1 ratio. The selected doses/schedules will be evaluated for safety (drug-related AEs), efficacy (including hematologic response), PD (long interspersed nucleotide element-1 (LINE-1 methylation, and fetal hemoglobin as fraction of total hemoglobin), and PK.

Conditions

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Myelodysplastic Syndromes

Keywords

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low risk myelodysplastic syndromes, MDS, ASTX727

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Multicenter, open label
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1 Stage A

3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD

Group Type EXPERIMENTAL

ASTX727 LD

Intervention Type DRUG

oral decitabine (LD) + cedazuridine (E7727)

Phase 1 Stage B

3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD

Group Type EXPERIMENTAL

ASTX727 LD

Intervention Type DRUG

oral decitabine (LD) + cedazuridine (E7727)

Phase 2

80 additional subjects randomized in a 1:1 ratio studying two different doses

Group Type EXPERIMENTAL

ASTX727 LD

Intervention Type DRUG

oral decitabine (LD) + cedazuridine (E7727)

ASTX727 SD

Intervention Type DRUG

oral decitabine (SD) + cedazuridine (E7727)

Interventions

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ASTX727 LD

oral decitabine (LD) + cedazuridine (E7727)

Intervention Type DRUG

ASTX727 SD

oral decitabine (SD) + cedazuridine (E7727)

Intervention Type DRUG

Other Intervention Names

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oral decitabine (LD) + cedazuridine (E7727) oral decitabine (SD) + cedazuridine (E7727)

Eligibility Criteria

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Inclusion Criteria

1. Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
2. Men or women ≥18 years with IPSS low risk or Int-1 MDS (all subjects). Subjects must have had at least 1 of the following disease-related criteria during the 8 weeks before randomization:

1. Red blood cell (RBC) transfusion dependence of 2 or more units of RBC transfusions (RBC transfusion administered for hemoglobin (Hb) levels ≤9.0 g/dL are counted).
2. Hb of \<9.0 g/dL in at least 2 blood counts prior to randomization or in 1 blood count if RBC transfusion was received.
3. Absolute Neutrophil Count (ANC) of \<0.5 × 10\^9/L in at least 2 blood counts prior to randomization.
4. Platelet counts of \<50 × 10\^9/L in at least 2 blood counts prior to randomization.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
4. Adequate organ function.
5. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group \[CTFG\]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
6. Women of child-bearing potential must agree to use contraceptive measures of birth control for 6 months after completing treatment; men must use contraceptive measures and agree not to father a child for at least 3 months after completing treatment.

Exclusion Criteria

1. Treatment with any investigational drug or therapy within 2 weeks before study treatment.
2. Treatments for MDS must be concluded 1 month prior to study treatment.
3. Prior treatment with azacitidine, decitabine, or guadecitabine.
4. Diagnosis of chronic myelomonocytic leukemia (CMML).
5. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
6. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 1 year.
7. Known active infection with human immunodeficiency virus or hepatitis viruses.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Colorado, Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status

BRCR Medical Center Inc.

Plantation, Florida, United States

Site Status

Moffitt Cancer Center Site#507

Tampa, Florida, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Indiana University Health Hospital - Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Clinical Research Center

Westwood, Kansas, United States

Site Status

The Center for Cancer and Blood Disorders (RCCA MD LLC - Maryland Division)

Bethesda, Maryland, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Oregon Health and Science University Knight Cancer Institute

Portland, Oregon, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center - Hematology-Oncology

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

ZNA - Campus Middelheim

Antwerp, , Belgium

Site Status

Az St-Jan Brugge-Oostende A.V.

Bruges, , Belgium

Site Status

London Regional Cancer Center

London, Ontario, Canada

Site Status

University of Alberta Hospital - Hematology Research

Edmonton, , Canada

Site Status

Universitaetsklinikum Freiburg Site#703

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum Halle

Halle, , Germany

Site Status

Universita degli Studi di Firenze

Florence, , Italy

Site Status

Hospital Universitario Vall d Hebron

Barcelona, , Spain

Site Status

Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Univeristario y Politecnico La Fe Servicio de Hematologia

Valencia, , Spain

Site Status

Countries

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United States Belgium Canada Germany Italy Spain

Other Identifiers

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ASTX727-03

Identifier Type: -

Identifier Source: org_study_id