- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03502668
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Antwerp, Belgium
- Zna - Campus Middelheim
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Brugge, Belgium
- Az St-Jan Brugge-Oostende A.V.
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Edmonton, Canada, T6G 2B7
- University of Alberta Hospital - Hematology Research
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Ontario
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London, Ontario, Canada, N6A 5W9
- London Regional Cancer Center
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Freiburg, Germany, 79106
- Universitaetsklinikum Freiburg Site#703
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Halle, Germany, 06120
- Universitätsklinikum Halle
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Firenze, Italy
- Università degli studi di Firenze
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Barcelona, Spain
- Hospital Universitario Vall D Hebron
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Barcelona, Spain
- Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol
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Madrid, Spain
- Hospital General Universitario Gregorio Marañon
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Valencia, Spain, 46026
- Hospital Univeristario y Politecnico La Fe Servicio de Hematologia
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Alabama
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Birmingham, Alabama, United States, 35233
- The University of Alabama at Birmingham
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado, Anschutz Cancer Pavilion
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Connecticut
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New Haven, Connecticut, United States, 06510
- Yale Cancer Center
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic Florida
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Plantation, Florida, United States, 33324
- BRCR Medical Center Inc.
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center Site#507
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Illinois
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Chicago, Illinois, United States, 60637
- The University Of Chicago
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University Health Hospital - Simon Cancer Center
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Kansas
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Westwood, Kansas, United States, 66205
- University of Kansas Clinical Research Center
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Maryland
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Bethesda, Maryland, United States, 20817
- The Center for Cancer and Blood Disorders (RCCA MD LLC - Maryland Division)
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Nebraska
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Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
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New York
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Buffalo, New York, United States, 14263
- Roswell Park Comprehensive Cancer Center
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Science University Knight Cancer Institute
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center - Hematology-Oncology
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Texas
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Houston, Texas, United States, 77030
- The University of Texas MD Anderson Cancer Center
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Tyler, Texas, United States, 75702
- Texas Oncology - Tyler
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Phase 1 Stage A
3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD
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oral decitabine (LD) + cedazuridine (E7727)
Other Names:
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Experimental: Phase 1 Stage B
3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD
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oral decitabine (LD) + cedazuridine (E7727)
Other Names:
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Experimental: Phase 2
80 additional subjects randomized in a 1:1 ratio studying two different doses
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oral decitabine (LD) + cedazuridine (E7727)
Other Names:
oral decitabine (SD) + cedazuridine (E7727)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule
Time Frame: 18-24 months
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Phase 1: Safety
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18-24 months
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Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Time Frame: 18-24 months
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Phase 2: Efficacy
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18-24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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%LINE-1 methylation change from baseline
Time Frame: 18-24 months
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pharmacodynamics
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18-24 months
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Area under the curve (AUC)
Time Frame: 18-24 months
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pharmacokinetics parameter
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18-24 months
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Maximum plasma concentration (Cmax)
Time Frame: 18-24 months
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pharmacokinetics parameter
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18-24 months
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Time to reach maximum concentration (Tmax)
Time Frame: 18-24 months
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pharmacokinetics parameter
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18-24 months
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Half life (t1/2)
Time Frame: 18-24 months
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pharmacokinetics parameter
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18-24 months
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Hematologic response (Phase 1 only) based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Time Frame: 18-24 months
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Phase 1: Efficacy
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18-24 months
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Time to bone marrow blasts >5%
Time Frame: 18-24 months
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Number of days from the date of randomization to the date when bone marrow blasts are >5% and increased by ≥50%.
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18-24 months
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Leukemia-free survival
Time Frame: 18-24 months
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Number of days from the date of randomization to the date when bone marrow or peripheral blood blasts reach ≥20%, or death from any cause
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18-24 months
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Overall survival
Time Frame: 18-24 months
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Number of days from the date of randomization to the date of death from any cause
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18-24 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Preleukemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine
- Decitabine and cedazuridine drug combination
Other Study ID Numbers
- ASTX727-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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