Study of ASTX727 vs IV Decitabine in Participants With MDS, CMML, and AML
A Phase 3, Randomized, Open-Label, Crossover Study of ASTX727 (Cedazuridine and Decitabine Fixed-Dose Combination) Versus IV Decitabine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), and Acute Myeloid Leukemia (AML)
2 other identifiers
interventional
227
10 countries
84
Brief Summary
Multicenter PK study of ASTX727 versus IV decitabine. Adult participants who were candidates to receive IV decitabine were randomized 1:1 to receive the ASTX727 tablet Daily×5 in Cycle 1 followed by IV decitabine 20 mg/m\^2 Daily×5 in Cycle 2, or the converse order. After completion of PK studies during the first 2 treatment cycles, participants continued to receive treatment with ASTX727 from Cycle 3 onward (in 28-day cycles) until disease progression, unacceptable toxicity, or the participants discontinued treatment or withdrew from the study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Feb 2018
Longer than P75 for phase_3
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2017
CompletedFirst Posted
Study publicly available on registry
October 11, 2017
CompletedStudy Start
First participant enrolled
February 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 10, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 25, 2023
CompletedResults Posted
Study results publicly available
July 1, 2024
CompletedAugust 27, 2024
July 1, 2024
3.6 years
October 2, 2017
April 10, 2024
July 31, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Total 5-day Area Under the Curve From 0 to 24 Hours (AUC0-24) After Treatment With ASTX727 And IV Decitabine
Total 5-day ASTX727 AUC0-24 exposures were calculated using PK data from 3 days of serial PK sampling, Day 1 AUC0-24 (first ASTX727 dose) was added to (Day 2 AUC0-24+ Day 5 AUC0-24) × 2. Decitabine 5-day AUC0-24 exposures after IV decitabine were calculated as follows: (Day 1 AUC0-24+ Day 5 AUC0-24) / 2 was multiplied by 5. If AUC0-24 on Day 2 (for ASTX727) or Day 1 (IV decitabine) was not available, it was replaced by AUC0-24 on Day 5; the converse was also true.
ASTX727: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24 hours post-dose on Days 1 to 5 of Cycle 1 and 2; Decitabine: Pre-dose, 0.25, 0.5, 1, 1.08, 1.5, 2, 3, 4, 6, 8 hours post-dose on Days 1 to 5 of Cycle 1 and 2 (each cycle= 28 days)
Secondary Outcomes (27)
MDS/CMML: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
From randomization up to 30 days after last dose of study treatment (up to approximately 2.7 years)
AML: Number of Participants With Treatment-emergent Adverse Events (AEs)
From randomization up to 30 days after last dose of study treatment (up to approximately 2.4 years)
MDS/CMML: Number of Participants With Grade 3 or Higher TEAEs
From randomization up to 30 days after last dose of study treatment (up to approximately 2.7 years)
AML: Number of Participants With Grade 3 or Higher TEAEs
From randomization up to 30 days after last dose of study treatment (up to approximately 2.4 years)
Maximum Percentage of Long Interspersed Nucleotide Elements (LINE)-1 Demethylation
Pre-dose on Day 1 of Cycles 1 and 2 (as Baseline), and Days 8, 15 and 22 of Cycles 1 and 2 (each cycle= 28 days)
- +22 more secondary outcomes
Study Arms (4)
MDS or CMML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727
EXPERIMENTALParticipants with MDS or CMML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days), followed by IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, treatment discontinuation for other reasons, or withdrawal from the study.
MDS or CMML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
EXPERIMENTALParticipants with MDS or CMML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days) followed by ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, treatment discontinuation for other reasons, or withdrawal from the study.
AML: Sequence A: First ASTX727, Then IV Decitabine, Then ASTX727
EXPERIMENTALParticipants with AML received ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days), followed by IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, participant discontinued treatment, or was withdrawn from the study.
AML: Sequence B: First IV Decitabine, Then ASTX727, Then ASTX727
EXPERIMENTALParticipants with AML received IV infusion of decitabine 20 mg/m\^2, once daily, on Days 1 to 5 in cycle 1 (each cycle = 28 days) followed by ASTX727 tablet, containing the fixed-dose combination of 35 mg decitabine and 100 mg cedazuridine, orally, once daily, on Days 1 to 5 in cycle 2. A washout period of 23 days was maintained between the 2 cycles. From cycle 3, all participants enrolled in cycles 1 and 2 received ASTX727 tablet, once daily, on Days 1 to 5 of each 28-day cycle until disease progression, unacceptable toxicity, participant discontinued treatment, or was withdrawn from the study.
Interventions
ASTX727 oral tablet
Decitabine 20 mg/m\^2 one-hour IV infusion
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; specifically able to comply with the PK assessment schedule during the first 2 treatment cycles.
- Men or women ≥18 years who are candidates to receive IV decitabine according to FDA or European Medicines Agency (EMA) approved indications:
- In North America: Participants with MDS previously treated or untreated with de novo or secondary 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, and chronic myelomonocytic leukemia \[CMML\]), and subjects with MDS International Prognostic Scoring System (IPSS) int-1, -2, or high-risk MDS.
- In Europe: Participants with de novo or secondary AML, as defined by the World Health Organization (WHO) criteria, who are not candidates for standard induction chemotherapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Adequate organ function defined as follows:
- Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤2.5 × ULN.
- Renal: serum creatinine ≤1.5 × ULN or calculated creatinine clearance or glomerular filtration rate \>50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
- No major surgery within 30 days of first study treatment.
- Life expectancy of at least 3 months.
- Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause, defined as no menses for at least 1 year AND either age ≥65 years or follicle-stimulating hormone levels in the menopausal range.
- Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months after the last dose of study treatment. Effective contraception includes methods such as oral contraceptives or double-barrier method (eg, use of a condom AND diaphragm, with spermicide).
You may not qualify if:
- Prior treatment with more than 1 cycle of azacitidine or decitabine. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
- Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection in the 30 days before screening.
- Treatment with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment.
- Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment.
- Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. (Prior treatment with these agents is permitted, provided that completion is at least 1 week before the first dose of study treatment.)
- Poor medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the patient at risk of not being able to complete at least 2 cycles of treatment.
- Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the subject to high risk of noncompliance with the protocol.
- Rapidly progressive or highly proliferative disease (total white blood cell count of \>15 × 10\^9/L) or other criteria that render the subject at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months.
- Life-threatening illness or severe organ system dysfunction, such as uncontrolled congestive heart failure or chronic obstructive pulmonary disease, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ASTX727, or compromise completion of the study or integrity of the study outcomes.
- 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 2 years.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (84)
Pinnacle Research Group
Anniston, Alabama, 36207, United States
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
Arizona Clinical Research Center
Tucson, Arizona, 85715, United States
Compassionate Cancer Care Research Group
Fountain Valley, California, 92708, United States
University of Southern California
Los Angeles, California, 90007, United States
Yale
New Haven, Connecticut, 06510, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Boca Raton Clinical Research
Boca Raton, Florida, 33322, United States
Holy Cross Hospital
Fort Lauderdale, Florida, 33308, United States
Mount Sinai
Miami Beach, Florida, 33140, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Chicago
Chicago, Illinois, 60637, United States
Quincy Medical Group
Quincy, Illinois, 62301, United States
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, 46237, United States
Norton Cancer Institute
Louisville, Kentucky, 40207, United States
Johns Hopkins
Baltimore, Maryland, 21287, United States
Regional Cancer Care Associates
Bethesda, Maryland, 20817, United States
Michigan Center of Medical Research
Farmington Hills, Michigan, 48334, United States
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Hackensack
Hackensack, New Jersey, 07601, United States
Roswell Park
Buffalo, New York, 14263, United States
Monter Cancer Center
Lake Success, New York, 11042, United States
Weill Cornell Medicine
New York, New York, 10065, United States
Montefiore
The Bronx, New York, 10467, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
Ohio State University
Columbus, Ohio, 43210, United States
Oregon Health & Sciences University
Portland, Oregon, 20817, United States
West Penn Allegheny Cancer Institute
Pittsburgh, Pennsylvania, 15224, United States
University of Pittsburgh Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Charleston Hematology Oncology Associates
Charleston, South Carolina, 29414, United States
Vanderbilt
Nashville, Tennessee, 37232, United States
Baylor Scott & White University Medical Center
Dallas, Texas, 75246, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-9179, United States
Houston Methodist Cancer Center
Houston, Texas, 77030, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84124, United States
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Uniklinikum Salzburg
Salzburg, 05020, Austria
General Hospital Hietzing
Vienna, 01130, Austria
Klinikum Wels-Grieskirchen
Wels, 4600, Austria
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
Queen Elizabeth II (QEII) Health Sciences Center
Halifax, Nova Scotia, B3H 2Y9, Canada
Juravinski Hospital & Cancer Center
Hamilton, Ontario, L8V 1C3, Canada
Ottawa Hospital - General Campus
Ottawa, Ontario, K1H8L6, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Center - University Health Network
Toronto, Ontario, M5G 2M9, Canada
Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Est-de-l'Ile-de-Montréal - Hôpital Maisonneuve Rosemont
Montreal, Quebec, H1T 2M4, Canada
FN Ostrava
Ostrava, Poruba, 708 00, Czechia
University Hospital Brno
Brno, 62500, Czechia
Fakultni Nemocnice Kralovske Vinohrady FNKV
Prague, Česká Republika, 10034, Czechia
Centre de lutte contre le Cancer Leon Berard
Lyon, Rhone, 69008, France
Hospital Emile Muller
Mulhouse, 68100, France
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Baden, 79106, Germany
Philipps-Universität Marburg, Klinik für Innere medizin, Hämatologie, Onkologie und Immunologie
Marburg, Hesse, 35033, Germany
UNIVERSITTSKLINIKUM Schleswig-Holstein
Lübeck, Schleswig-Holstein, 23538, Germany
Staedtisches Klinikum Braunschweig
Braunschweig, 38114, Germany
Oberärztin für Innere Medizin, Hämato-/Onkologie und Palliativmedizin
Düsseldorf, 40479, Germany
University Hospital Halle
Halle, 06120, Germany
University of Leipzig
Leisnig, 04103, Germany
Debreceni Egyetem Klinikai Kozpont
Debrecen, 4032, Hungary
Somogy Megyei KAposi Mor Oktato Korhaz
Kaposvár, 7400, Hungary
University of Pecs, 1st Department of Internal Medicine
Pécs, 7400, Hungary
University of Szeged
Szeged, 6725, Hungary
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
Alessandria, 15121, Italy
AOUC Azienda Ospedaliero-Universitaria Careggi
Florence, 50134, Italy
Fondazione IRCCS C Granda OM Policlinico
Milan, 20122, Italy
Azienda Ospedaliero-Universitaria Maggiore della Carità Novara
Novara, 28100, Italy
Ospedale S. Eugenio
Rome, 00144, Italy
ULSS 8 Vicenza - Ospedale San Bortolo di Vicenza
Vicenza, 36100, Italy
Hospital U. Marqués de Valdecilla
Santander, Cantabria, 39008, Spain
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011, Spain
Hospital San Pedro de Alcantara
Cáceres, 10003, Spain
Hospital Universitario Virgen de las Nieves
Granada, 18012, Spain
Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08909, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Clinica Universitaria Navarra
Madrid, 28027, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Clinica Universitaria Navarra
Pamplona, 31008, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitari I Politècnic La Fe
Valencia, 46026, Spain
Oxford University Hopsitals NHS Trust
Oxford, Oxfordshire, OX3 7LE, United Kingdom
The Christie NHS Fundation Trust
Manchester, M20 4BX, United Kingdom
Related Publications (1)
Garcia-Manero G, McCloskey J, Griffiths EA, Yee KWL, Zeidan AM, Al-Kali A, Deeg HJ, Patel PA, Sabloff M, Keating MM, Zhu N, Gabrail NY, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern AE, O'Connell CL, Roboz GJ, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao KH, Oganesian A, Hao Y, Keer HN, Azab M, Savona MR. Oral decitabine-cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukaemia (ASCERTAIN): a registrational, randomised, crossover, pharmacokinetics, phase 3 study. Lancet Haematol. 2024 Jan;11(1):e15-e26. doi: 10.1016/S2352-3026(23)00338-1.
PMID: 38135371DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Taiho Central
- Organization
- Taiho Oncology, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 2, 2017
First Posted
October 11, 2017
Study Start
February 15, 2018
Primary Completion
September 10, 2021
Study Completion
May 25, 2023
Last Updated
August 27, 2024
Results First Posted
July 1, 2024
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will not share