Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS
A Randomized, Open-Label, Phase 1-2 Study of ASTX727 Low Dose (ASTX727 LD) Extended Schedule in Subjects With Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)
1 other identifier
interventional
160
6 countries
29
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2018
Longer than P75 for phase_1
29 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
April 11, 2018
CompletedFirst Posted
Study publicly available on registry
April 19, 2018
CompletedStudy Start
First participant enrolled
July 27, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 13, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
January 13, 2026
CompletedMarch 10, 2026
March 1, 2026
7.5 years
April 11, 2018
March 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule
Phase 1: Safety
18-24 months
Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Phase 2: Efficacy
18-24 months
Secondary Outcomes (9)
%LINE-1 methylation change from baseline
18-24 months
Area under the curve (AUC)
18-24 months
Maximum plasma concentration (Cmax)
18-24 months
Time to reach maximum concentration (Tmax)
18-24 months
Half life (t1/2)
18-24 months
- +4 more secondary outcomes
Study Arms (3)
Phase 1 Stage A
EXPERIMENTAL3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD
Phase 1 Stage B
EXPERIMENTAL3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD
Phase 2
EXPERIMENTAL80 additional subjects randomized in a 1:1 ratio studying two different doses
Interventions
oral decitabine (LD) + cedazuridine (E7727)
oral decitabine (SD) + cedazuridine (E7727)
Eligibility Criteria
You may qualify if:
- 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.
- 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:
- 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).
- 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.
- Absolute Neutrophil Count (ANC) of \<0.5 × 10\^9/L in at least 2 blood counts prior to randomization.
- Platelet counts of \<50 × 10\^9/L in at least 2 blood counts prior to randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Adequate organ function.
- 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.
- 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.
You may not qualify if:
- Treatment with any investigational drug or therapy within 2 weeks before study treatment.
- Treatments for MDS must be concluded 1 month prior to study treatment.
- Prior treatment with azacitidine, decitabine, or guadecitabine.
- Diagnosis of chronic myelomonocytic leukemia (CMML).
- Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
- 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.
- Known active infection with human immunodeficiency virus or hepatitis viruses.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (29)
The University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
University of Colorado, Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Yale Cancer Center
New Haven, Connecticut, 06510, United States
Mayo Clinic Florida
Jacksonville, Florida, 32224, United States
BRCR Medical Center Inc.
Plantation, Florida, 33324, United States
Moffitt Cancer Center Site#507
Tampa, Florida, 33612, United States
The University of Chicago
Chicago, Illinois, 60637, United States
Indiana University Health Hospital - Simon Cancer Center
Indianapolis, Indiana, 46202, United States
University of Kansas Clinical Research Center
Westwood, Kansas, 66205, United States
The Center for Cancer and Blood Disorders (RCCA MD LLC - Maryland Division)
Bethesda, Maryland, 20817, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263, United States
Oregon Health and Science University Knight Cancer Institute
Portland, Oregon, 97239, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center - Hematology-Oncology
Nashville, Tennessee, 37232, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Oncology - Tyler
Tyler, Texas, 75702, United States
ZNA - Campus Middelheim
Antwerp, Belgium
Az St-Jan Brugge-Oostende A.V.
Bruges, Belgium
London Regional Cancer Center
London, Ontario, N6A 5W9, Canada
University of Alberta Hospital - Hematology Research
Edmonton, T6G 2B7, Canada
Universitaetsklinikum Freiburg Site#703
Freiburg im Breisgau, 79106, Germany
Universitätsklinikum Halle
Halle, 06120, Germany
Universita degli Studi di Firenze
Florence, Italy
Hospital Universitario Vall d Hebron
Barcelona, Spain
Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol
Barcelona, Spain
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Hospital Univeristario y Politecnico La Fe Servicio de Hematologia
Valencia, 46026, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 11, 2018
First Posted
April 19, 2018
Study Start
July 27, 2018
Primary Completion
January 13, 2026
Study Completion
January 13, 2026
Last Updated
March 10, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share