Ignite Creation Date:
2025-12-24 @ 5:50 PM
Ignite Modification Date:
2025-12-27 @ 10:50 PM
Study NCT ID:
NCT03502668
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-05
First Post:
2018-04-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}], 'ancestors': [{'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077209', 'term': 'Decitabine'}, {'id': 'C000633944', 'term': 'cedazuridine'}], 'ancestors': [{'id': 'D001374', 'term': 'Azacitidine'}, {'id': 'D001372', 'term': 'Aza Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D012263', 'term': 'Ribonucleosides'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Multicenter, open label'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 160}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2018-07-27', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-04', 'studyFirstSubmitDate': '2018-04-11', 'studyFirstSubmitQcDate': '2018-04-11', 'lastUpdatePostDateStruct': {'date': '2025-12-05', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2018-04-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule', 'timeFrame': '18-24 months', 'description': 'Phase 1: Safety'}, {'measure': 'Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)', 'timeFrame': '18-24 months', 'description': 'Phase 2: Efficacy'}], 'secondaryOutcomes': [{'measure': '%LINE-1 methylation change from baseline', 'timeFrame': '18-24 months', 'description': 'pharmacodynamics'}, {'measure': 'Area under the curve (AUC)', 'timeFrame': '18-24 months', 'description': 'pharmacokinetics parameter'}, {'measure': 'Maximum plasma concentration (Cmax)', 'timeFrame': '18-24 months', 'description': 'pharmacokinetics parameter'}, {'measure': 'Time to reach maximum concentration (Tmax)', 'timeFrame': '18-24 months', 'description': 'pharmacokinetics parameter'}, {'measure': 'Half life (t1/2)', 'timeFrame': '18-24 months', 'description': 'pharmacokinetics parameter'}, {'measure': 'Hematologic response (Phase 1 only) based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)', 'timeFrame': '18-24 months', 'description': 'Phase 1: Efficacy'}, {'measure': 'Time to bone marrow blasts >5%', 'timeFrame': '18-24 months', 'description': 'Number of days from the date of randomization to the date when bone marrow blasts are \\>5% and increased by ≥50%.'}, {'measure': 'Leukemia-free survival', 'timeFrame': '18-24 months', 'description': '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'}, {'measure': 'Overall survival', 'timeFrame': '18-24 months', 'description': 'Number of days from the date of randomization to the date of death from any cause'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['low risk myelodysplastic syndromes, MDS, ASTX727'], 'conditions': ['Myelodysplastic Syndromes']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nPhase 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.\n\nPhase 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. 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.\n2. 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:\n\n 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).\n 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.\n 3. Absolute Neutrophil Count (ANC) of \\<0.5 × 10\\^9/L in at least 2 blood counts prior to randomization.\n 4. Platelet counts of \\<50 × 10\\^9/L in at least 2 blood counts prior to randomization.\n3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n4. Adequate organ function.\n5. 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.\n6. 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.\n\nExclusion Criteria:\n\n1. Treatment with any investigational drug or therapy within 2 weeks before study treatment.\n2. Treatments for MDS must be concluded 1 month prior to study treatment.\n3. Prior treatment with azacitidine, decitabine, or guadecitabine.\n4. Diagnosis of chronic myelomonocytic leukemia (CMML).\n5. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.\n6. 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.\n7. Known active infection with human immunodeficiency virus or hepatitis viruses.'}, 'identificationModule': {'nctId': 'NCT03502668', 'briefTitle': 'Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS', 'organization': {'class': 'INDUSTRY', 'fullName': 'Taiho Oncology, Inc.'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'ASTX727-03'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Phase 1 Stage A', 'description': '3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD', 'interventionNames': ['Drug: ASTX727 LD']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 1 Stage B', 'description': '3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD', 'interventionNames': ['Drug: ASTX727 LD']}, {'type': 'EXPERIMENTAL', 'label': 'Phase 2', 'description': '80 additional subjects randomized in a 1:1 ratio studying two different doses', 'interventionNames': ['Drug: ASTX727 LD', 'Drug: ASTX727 SD']}], 'interventions': [{'name': 'ASTX727 LD', 'type': 'DRUG', 'otherNames': ['oral decitabine (LD) + cedazuridine (E7727)'], 'description': 'oral decitabine (LD) + cedazuridine (E7727)', 'armGroupLabels': ['Phase 1 Stage A', 'Phase 1 Stage B', 'Phase 2']}, {'name': 'ASTX727 SD', 'type': 'DRUG', 'otherNames': ['oral decitabine (SD) + cedazuridine (E7727)'], 'description': 'oral decitabine (SD) + cedazuridine (E7727)', 'armGroupLabels': ['Phase 2']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35233', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'The University of Alabama at Birmingham', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado, Anschutz Cancer Pavilion', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '06510', 'city': 'New Haven', 'state': 'Connecticut', 'country': 'United States', 'facility': 'Yale Cancer Center', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '32224', 'city': 'Jacksonville', 'state': 'Florida', 'country': 'United States', 'facility': 'Mayo Clinic Florida', 'geoPoint': {'lat': 30.33218, 'lon': -81.65565}}, {'zip': '33324', 'city': 'Plantation', 'state': 'Florida', 'country': 'United States', 'facility': 'BRCR Medical Center Inc.', 'geoPoint': {'lat': 26.13421, 'lon': -80.23184}}, {'zip': '33612', 'city': 'Tampa', 'state': 'Florida', 'country': 'United States', 'facility': 'Moffitt Cancer Center Site#507', 'geoPoint': {'lat': 27.94752, 'lon': -82.45843}}, {'zip': '60637', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'The University of Chicago', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '46202', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'Indiana University Health Hospital - Simon Cancer Center', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '66205', 'city': 'Westwood', 'state': 'Kansas', 'country': 'United States', 'facility': 'University of Kansas Clinical Research Center', 'geoPoint': {'lat': 39.04056, 'lon': -94.6169}}, {'zip': '20817', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'The Center for Cancer and Blood Disorders (RCCA MD LLC - Maryland Division)', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}, {'zip': '55905', 'city': 'Rochester', 'state': 'Minnesota', 'country': 'United States', 'facility': 'Mayo Clinic', 'geoPoint': {'lat': 44.02163, 'lon': -92.4699}}, {'zip': '68198', 'city': 'Omaha', 'state': 'Nebraska', 'country': 'United States', 'facility': 'University of Nebraska Medical Center', 'geoPoint': {'lat': 41.25626, 'lon': -95.94043}}, {'zip': '14263', 'city': 'Buffalo', 'state': 'New York', 'country': 'United States', 'facility': 'Roswell Park Comprehensive Cancer Center', 'geoPoint': {'lat': 42.88645, 'lon': -78.87837}}, {'zip': '97239', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health and Science University Knight Cancer Institute', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '37203', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Sarah Cannon Research Institute', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt University Medical Center - Hematology-Oncology', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas MD Anderson Cancer Center', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '75702', 'city': 'Tyler', 'state': 'Texas', 'country': 'United States', 'facility': 'Texas Oncology - Tyler', 'geoPoint': {'lat': 32.35126, 'lon': -95.30106}}, {'city': 'Antwerp', 'country': 'Belgium', 'facility': 'ZNA - Campus Middelheim', 'geoPoint': {'lat': 51.22047, 'lon': 4.40026}}, {'city': 'Bruges', 'country': 'Belgium', 'facility': 'Az St-Jan Brugge-Oostende A.V.', 'geoPoint': {'lat': 51.20892, 'lon': 3.22424}}, {'zip': 'N6A 5W9', 'city': 'London', 'state': 'Ontario', 'country': 'Canada', 'facility': 'London Regional Cancer Center', 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}, {'zip': 'T6G 2B7', 'city': 'Edmonton', 'country': 'Canada', 'facility': 'University of Alberta Hospital - Hematology Research', 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'zip': '79106', 'city': 'Freiburg im Breisgau', 'country': 'Germany', 'facility': 'Universitaetsklinikum Freiburg Site#703', 'geoPoint': {'lat': 47.9959, 'lon': 7.85222}}, {'zip': '06120', 'city': 'Halle', 'country': 'Germany', 'facility': 'Universitätsklinikum Halle', 'geoPoint': {'lat': 51.48158, 'lon': 11.97947}}, {'city': 'Florence', 'country': 'Italy', 'facility': 'Universita degli Studi di Firenze', 'geoPoint': {'lat': 43.77925, 'lon': 11.24626}}, {'city': 'Barcelona', 'country': 'Spain', 'facility': 'Hospital Universitario Vall d Hebron', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'city': 'Barcelona', 'country': 'Spain', 'facility': "Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol", 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'city': 'Madrid', 'country': 'Spain', 'facility': 'Hospital General Universitario Gregorio Marañón', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'zip': '46026', 'city': 'Valencia', 'country': 'Spain', 'facility': 'Hospital Univeristario y Politecnico La Fe Servicio de Hematologia', 'geoPoint': {'lat': 39.47391, 'lon': -0.37966}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Taiho Oncology, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}