Myelodysplastic SyndromesPhase 2/3NCT04256317
A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)
A Phase 2/3 study testing Azacitidine, ASTX030 (cedazuridine + azacitidine) and Cedazuridine in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Taiho Oncology, Inc. at 73 sites in 10 countries.
Trial summary
Study ASTX030-01 is a multi-phase study comprising of Phases 1-3 Monotherapy arms, and Phase 1 and Phase 2 Combination Therapy arms. Phase 1 Monotherapy consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myelodysplastic Syndrome/Neoplasm
- What is being tested?
- Azacitidine, ASTX030 (cedazuridine + azacitidine) and Cedazuridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 73 sitesin 10 countries
- Study dates
- 21 May 2020to 1 Nov 2028
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase 2 Monotherapy:
- 1. Has Confirmed MDS, CMML, or other MDS/MPN diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice.
- Phase 3 Monotherapy:
- Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice:
- French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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- Participants with adequate organ function.
- For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
- Participants with no major surgery within 3 weeks before first study treatment.
- Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.
- Is able to swallow the number of tablets/capsules required for the treatment assignment within a 10-minute period and tolerate 4 hours of fasting.
- Participants with projected life expectancy of at least 12 weeks.
- Phase 1 and Phase 2 Combination Therapy:
- Has histological confirmation of newly diagnosed AML by World Health Organization (WHO) 2022 criteria (Phase 1) or 2016 criteria (Phase 2).
- Participants with projected life expectancy of at least 12 weeks.
- Must be considered ineligible for intensive induction chemotherapy defined by the following:
- Aged 75 years or older, or b. Aged 18 to 74 years with at least one of the following comorbidities: i. Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
- Severe pulmonary disorder (e.g., diffusing capacity of the lung for carbon monoxide (DLCO) ≤65% or forced expiratory volume in 1 second [FEV1] ≤65%). iii. Creatinine clearance ≥30 mL/min to <45 mL/min. iv. Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0 × upper limit of normal (ULN).
- ECOG Performance Status of 2 or 3.
- Has an ECOG Performance Status of 0-2 for participants ≥75 years of age or 0-3 for participants 18 to 74 years of age.
Who cannot join
- All Monotherapy Phases:
- Has an active uncontrolled gastric or duodenal ulcer.
- Has poor medical risk because of other conditions.
- Has known human immunodeficiency virus (HIV) infection.
- Is known to be positive for Hepatitis B or C infection.
- Has a life-threatening illness.
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- Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
- Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
- Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
- Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
- Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
- Cannot discontinue treatment with any drugs that delay gastric emptying such as glucagon-like peptide-1 (GLP-1) and/or gastric inhibitory polypeptide (GIP) agonists in Cycles 1 and 2 of the study.
- Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
- Phase 1 and Phase 2 Combination Therapy:
- Has a history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
- Has the following karyotype abnormalities: t(15;17) or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy [t(8;21) and inv(16) are excluded in Phase 2 only].
- Has known active central nervous system involvement from AML.
- Has known human immunodeficiency virus (HIV) infection.
- Is known to be positive for Hepatitis B or C infection.
- Has severe hepatic impairment
- Has severe renal impairment
- Has a malabsorption syndrome or other condition that precludes enteral route of administration.
- Has a cardiovascular disability status of New York Heart Association Class >2.
- Has significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease; or any other medical condition that in the opinion of the investigator would adversely affect his/her participation in this study.
- Has clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
- Has a history of other malignancies prior to study entry with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or adequately treated and controlled with other modalities); and any early stage malignancy for which no definitive therapy is required.
- Has a WBC count >25,000/ microliters (μL) (hydroxyurea treatment is permitted to meet this criterion).
- Has received treatment with any of the following:
- A hypomethylating agent (azacitidine or decitabine) or venetoclax, including prior treatment for MDS.
- Chimeric Antigen Receptor (CAR)-T cell therapy.
- Investigational therapies for MDS or AML.
- Cannot discontinue treatment with any of the following:
- Prophylactic antifungal therapy with CYP3A inhibitor activity or other concomitant medications with moderate or strong CYP3A inhibitor activity ≥7 days or 5 halflives, whichever is greater, prior to Cycle 1 Day 1 (C1D1).
- Drugs that are strong CYP3A or P-gp inhibitors ≥7 days or 5 half-lives, whichever is greater, prior to C1D1.
- Cannot avoid concomitant drugs known as moderate or strong CYP3A inducers.
- Cannot discontinue treatment with any drugs that delay gastric emptying such as GLP-1 and/or GIP agonists in Cycles 1 and 2 of the study.
- Is participating in another research study requiring interventions such as drug therapy or study procedures.
- Has a known or suspected hypersensitivity to cedazuridine, azacitidine, venetoclax, or any of their excipients.
- Has known significant mental illness or other conditions such as alcohol or other substance abuse or addictions
- Consumes grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit ≤7 days prior to C1D1.
Trial locations and contacts
73 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
73 sites in 10 countries
United States24 sites, 22 recruiting
- Recruiting
University of Emory - Winship Cancer Institute
Atlanta, Georgia, 30322
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02114
- Recruiting
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
- Recruiting
Hollings Cancer Center
Charleston, South Carolina, 29425
- Recruiting
Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
- Withdrawn
Baylor Research Institute dba Baylor Scott & White Research Institute
Dallas, Texas, 75204
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Duke University
Durham, North Carolina, 27705
- Recruiting
John Theurer Cancer Center / Hackensack University
Hackensack, New Jersey, 07601
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Keck School of Medicine of USC
Los Angeles, California, 90089
- Recruiting
University of Miami - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
- Recruiting
Froedtert & Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
New York University Langone Hospital - Long Island
Mineola, New York, 11501
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
Yale University
New Haven, Connecticut, 06510
- Recruiting
Perlmutter Cancer Center - 34th Street
New York, New York, 10016
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
- Withdrawn
Weill Cornell Medical Center
New York, New York, 10065
- Recruiting
UC Irvine Health - Chao Family Comprehensive Cancer Center
Orange, California, 92868
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
- Recruiting
Oregon Oncology Specialists
Salem, Oregon, 97301
- Recruiting
Seattle Cancer Care Alliance
Seattle, Washington, 98109
- Recruiting
Montefiore Medical Center
The Bronx, New York, 10467
Spain16 sites, 16 recruiting
- Recruiting
Institut Català d'Oncologia Badalona
Badalona, Barcelona, 08916
- Recruiting
Hospital Universitari Vall d'Hebrón
Barcelona, 08035
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
- Recruiting
Hospital San Pedro de Alcantara
Cáceres, 10003
- Recruiting
Institut Català d'Oncologia Girona (ICO Girona)
Girona, 17007
- Recruiting
Hospital Universitario Virgen de las Nieves
Granada, 18014
- Recruiting
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
L'Hospitalet de Llobregat, Barcelona, 08908
- Recruiting
Hospital General Universitario Gregorio Marañón
Madrid, 28007
- Recruiting
Clínica Universidad de Navarra - Madrid
Madrid, 28027
- Recruiting
MD Anderson Cancer Center Madrid
Madrid, 28033
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
- Recruiting
Hospital Quirónsalud Málaga
Málaga, 29004
- Not yet recruiting
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
- Recruiting
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre, 31008
- Recruiting
Complejo Asistencial Universitario de Salamanca - Hospital Clínico
Salamanca, 37007
- Recruiting
Hospital Universitari i Politècnic La Fe
Valencia, 46026
Italy9 sites, 9 recruiting
- Recruiting
Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant Orsola-Malpighi
Bologna, 40138
- Recruiting
Azienda Ospedaliero - Universitaria Careggi
Florence, Florence, 50134
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
- Recruiting
Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
Novara, 28100
- Recruiting
Ospedale Santa Maria delle Croci di Ravenna
Ravenna, Emilia-Romagna, 48121
- Recruiting
Fondazione PTV - Policlinico Tor Vergata
Roma, 00133
- Recruiting
Umberto I - Policlinico di Roma
Roma, 00161
- Recruiting
Azienda Ospedaliera Ordine Mauriziano di Torino
Torino, Turin, 10128
- Recruiting
Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino
Torino, 10126
United Kingdom5 sites, 5 recruiting
- Recruiting
King's College Hospital NHS Foundation Trust
London, England, SE5 9RS
- Not yet recruiting
Maidstone and Tunbridge Wells NHS Trust - Maidstone Hospital
Maidstone, England, ME16 9QQ
- Recruiting
The Christie NHS Foundation Trust
Manchester, England, M20 4GJ
- Not yet recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford, England, OX3 7LE
- Not yet recruiting
University Hospital Southampton NHS Foundation Trust
Southampton, England, SO16 6YD
Germany4 sites, 4 recruiting
- Recruiting
Städtisches Klinikum Braunschweig
Braunschweig, Lower Saxony, 38114
- Recruiting
Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106
- Recruiting
Universitätsklinikum Halle
Halle, Saxony-Anhalt, 06120
- Not yet recruiting
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Hungary4 sites, 4 recruiting
- Recruiting
Semmelweis Egyetem Belgyógyászati és Hematológiai Klinika
Budapest, 1088
- Recruiting
Debreceni Egyetem Klinikai Központ
Debrecen, Hajdú-Bihar, 4032
- Recruiting
Petz Aladár Győr-Moson-Sopron Vármegyei Egyetemi Oktató Kórház
Győr, Győr-Moson-Sopron, 9023
- Not yet recruiting
Szent-Györgyi Albert Klinikai Központ, II. sz. Belgyógyászati Klinika és Kardiológiai Központ
Szeged, Csongrád megye, 6725
Czechia3 sites, 3 recruiting
- Recruiting
Fakultni Nemocnice Ostrava
Ostrava, Moravian-Silesian, 708 52
- Recruiting
Fakultní Nemocnice Královské Vinohrady
Prague, Prague, 100 34
- Recruiting
Vseobecna Fakultni Nemocnice v Praze
Prague, Prague, 128 08
France3 sites, 3 recruiting
- Recruiting
Hôpital l'Archet
Nice, Provence-Alpes-Côte d'Azur Region, 06202
- Recruiting
Hôpital Saint-Louis
Paris, Île-de-France Region, 75010
- Recruiting
Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole
Toulouse, Haute-Garonne, 31059
Poland3 sites, 3 recruiting
- Recruiting
Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością
Gdynia, Pomeranian Voivodeship, 81-519
- Recruiting
Wojewódzkie Wielospecjalistyczne Centrum
Lodz, Lódzkie, 93-513
- Recruiting
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, Lublin Voivodeship, 20-081
Canada2 sites, 2 recruiting
- Recruiting
Eastern Health - Health Sciences Centre
St. John's, Newfoundland and Labrador, A1B 3V6
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2C1
About this study
Official title: A Multi-phase, Pharmacokinetics, Safety, and Efficacy Study of ASTX030 (Azacitidine and Cedazuridine) as Monotherapy in Subjects With Myeloid Neoplasm or in Combination With Venetoclax in Subjects With AML (AZTOUND Study)
Study ASTX030-01 is a multi-phase study comprising of Phases 1-3 Monotherapy arms, and Phase 1 and Phase 2 Combination Therapy arms. Phase 1 Monotherapy consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 Monotherapy is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 Monotherapy is a randomized open-label crossover study comparing the final fixed dose of oral ASTX030 to SC azacitidine. Phase 1 Combination Therapy is an open-label, multicenter, randomized, exploratory study comparing ASTX030 and SC azacitidine in combination with venetoclax in participants with treatment-naïve AML. Phase 2 Combination Therapy is an open-label, single arm, study evaluating the efficacy, safety, pharmacokinetics (PK), and drug interactions of ASTX030 in combination with venetoclax in participants with treatment-naïve AML.
The duration of this multi-phase study is approximately 8 years.
Read the detailed description
The Phase 1 and Phase 2 Monotherapy arms have completed enrollment. The Phase 3 Monotherapy, Phase 1 Combination Therapy, and Phase 2 Combination Therapy arms are open for enrollment.
- Conditions
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myelodysplastic Syndrome/Neoplasm, Chronic Myelomonocytic Leukemia
- Being tested
- Azacitidine, ASTX030 (cedazuridine + azacitidine), Cedazuridine, Venetoclax
- Keywords
- ASTX030, Myeloid Neoplasm, Hematologic Disease, Leukemia, Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), Vidaza™, Azacitidine, Azacitidine and cedazuridine drug combination, Venetoclax, Venclexta™
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts, Leukemia, Myelomonocytic, Chronic, Hematologic Diseases, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza™ (powder only)
Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.
ASTX030 (cedazuridine + azacitidine)Drug
FDC Capsules for oral administration.
AzacitidineDrug
Also called Vidaza™ (powder only)
Powder for reconstitution to aqueous suspension for SC administration.
ASTX030 (cedazuridine + azacitidine)Drug
Tablets/Capsules for oral administration.
CedazuridineDrug
Tablets for oral administration.
VenetoclaxDrug
Also called Venclexta™
Oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Monotherapy , Stage A (Dose Escalation) | Experimental | In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered. Receives: Drug: Azacitidine; Drug: ASTX030 (cedazuridine + azacitidine); Drug: Cedazuridine |
| Phase 1 Monotherapy, Stage B (Dose Expansion) | Experimental | In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered. On Day 7 of Cycle 2 drug products will administered in a fed state and all other doses will be administered in fasted state. Receives: Drug: Azacitidine; Drug: ASTX030 (cedazuridine + azacitidine); Drug: Cedazuridine |
| Phase 2 Monotherapy, Part B, Sequence A & B | Experimental | In Sequence A: Oral ASTX030 (cedazuridine + azacitidine) will be administered in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
In Sequence B: SC azacitidine will be administered in Cycle 1, followed by oral cedazuridine + azacitidine tablets/capsules in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). Receives: Drug: ASTX030 (cedazuridine + azacitidine); Drug: Azacitidine |
| Phase 3 Monotherapy, Sequence A & B | Experimental | In Sequence A: Participants will receive ASTX030 in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
In Sequence B: Participants will receive SC azacitidine in Cycle 1 followed by ASTX030 in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). Receives: Drug: ASTX030 (cedazuridine + azacitidine); Drug: Azacitidine |
| Phase 1 Combination Therapy | Experimental | Treatment Arm 1: Participants will receive oral dose of ASTX030 along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive ASTX030 along with venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2).
Treatment Arm 2: Participants will receive SC azacitidine along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive SC azacitidine along with oral dose of venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2). At the beginning of Cycle 5, Arm 2 patients may be permitted to cross over to Arm 1. Receives: Drug: ASTX030 (cedazuridine + azacitidine); Drug: Azacitidine; Drug: Venetoclax |
| Phase 2 Combination Therapy | Experimental | Participants will receive ASTX030 along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive ASTX030 along with venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2). Receives: Drug: ASTX030 (cedazuridine + azacitidine); Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1, 2 and 3 Monotherapy: Total Cycle Area Under the Curve (AUC) From 0 to 24 Hours (AUC0-24) Exposures
Ratio of azacitidine total cycle AUC0-24 exposures after oral ASTX030 over SC azacitidine.
Measured: Predose and at multiple timepoints post-dose up to 24 hours
Phase 1 Combination Therapy: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Measured: Up to 24 months
Phase 1 and 2 Combination Therapy: Complete Response (CR) Rate as Assessed by the Investigator
Measured: Up to 36 months
Phase 1 Combination Therapy: AUC0-24 of Venetoclax With ASTX030
Measured: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] of Cycle 1
Phase 1 Combination Therapy: AUC0-24 of Venetoclax Without ASTX030
Measured: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 14 (without ASTX030) of Cycle 1
Phase 1 Combination Therapy: Maximum Plasma Concentration (Cmax) of Venetoclax With ASTX030
Measured: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] of Cycle 1
Phase 1 Combination Therapy: Cmax of Venetoclax Without ASTX030
Measured: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 14 (without ASTX030) of Cycle 1
Secondary outcomes (34)
Phase 1, 2 and 3 Monotherapy: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: Change in Deoxyribonucleic Acid (DNA) Methylation
Percent long interspersed nuclear elements 1 (LINE-1) methylation change (demethylation) from baseline in Cycle 1 (Phase 1) and compared between SC azacitidine and ASTX030 in Cycles 1 and 2 (Phase 2 and 3).
Measured: Baseline in Phase 1 to the end of Cycle 2 in Phase 3 (28 days per cycle)
Phase 1, 2 and 3 Monotherapy: Best CR Rate in Participants with MDS, CMML, or MDS/Myeloproliferative Neoplasms (MPN)
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: AML-free Survival for Participants with MDS, CMML, or MDS/MPN
Number of days from the date of randomization (date of first treatment in Phase 1) to either the date of MDS, CMML, or MDS/MPN progression to AML or the date of death from any cause
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: Duration of Response
Number of days from the date that criteria are met for response until the first date that recurrent or progressive disease is documented by the investigating physician
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: Overall Survival
Number of days from the date the participant was randomized (date of first treatment in Phase 1) to the date of death, regardless of cause
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: Time to Response
Number of days from the start of treatment until the participant's first day of best response
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: Red Blood Cell (RBC) Transfusion Independence (TI)
Number of participants with RBC TI, defined as no RBC transfusion for 56 consecutive days while maintaining hemoglobin ≥8 g/dL
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: Platelet Transfusion Independence (TI)
Number of participants with platelet TI, defined as no platelet transfusion for 56 consecutive days while maintaining platelets ≥20×10^9/L
Measured: Up to 36 months
Phase 1, 2 and 3 Monotherapy: AUC of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Days 1, 2 and 7 of Cycle 1 and Cycle 2 (cycle length=28 days)
Phase 1, 2 and 3 Monotherapy: Cmax of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Days 1, 2 and 7 of Cycle 1 and Cycle 2 (cycle length=28 days)
Phase 1, 2 and 3 Monotherapy: Time to Reach Cmax (Tmax) of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Days 1, 2 and 7 of Cycle 1 and Cycle 2 (cycle length=28 days)
Phase 1B, Food Effect Cohort: AUC of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1B Monotherapy, Food Effect Cohort: Cmax of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1B Monotherapy, Food Effect Cohort: Tmax of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycle 2 (cycle length=28 days)
Phase 1 and 2 Combination Therapy: AUC0-24 of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose up to 24 hours on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: Cmax of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: Tmax of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: AUC0-9 of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose up to 9 hours on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: AUC0-inf of Azacitidine, Cedazuridine and Cedazuridine-epimer
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: AUC of SC Azacitidine and Venetoclax
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: AUC of Venetoclax, Azacitidine, and Cedazuridine
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: Cmax of SC Azacitidine and Venetoclax
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: Cmax of Venetoclax, Azacitidine, and Cedazuridine
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 Combination Therapy: Tmax of Venetoclax, Azacitidine, and Cedazuridine
Measured: Predose and at multiple timepoints post-dose on Day 7 of Cycles 1 and 2 (cycle length = 28 days)
Phase 1 and 2 Combination Therapy: CR and Complete Response with Partial Hematologic Recovery (CRh) Rate
Measured: Up to 36 months
Phase 1 and 2 Combination Therapy: CR and Complete Response with Incomplete Hematologic Recovery (CRi) Rate
Measured: Up to 36 months
Phase 1 and 2 Combination Therapy: Time to CR and CRh
Measured: Up to 36 months
Phase 2 Combination Therapy: AUC0-24 of Venetoclax With and Without ASTX030
Measured: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] and Day 14 (without ASTX030) of Cycle 1
Phase 2 Combination Therapy: Cmax of Venetoclax With and Without ASTX030
Measured: Time Frame: Pre-dose and at multiple timepoints post-dose up to 24 hours on Day 7 (with ASTX030] and Day 14 (without ASTX030) of Cycle 1
Phase 2 Combination Therapy: Number of Participants with TEAEs
Measured: Up to 36 months
Phase 2 Combination Therapy: Overall Survival (OS)
Measured: Up to 36 months
Phase 2 Combination Therapy: Event Free Survival (EFS)
Measured: Up to 36 months
Phase 2 Combination Therapy: Duration of CR and CRi or CRh
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start21 May 2020
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 316 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04256317
- Sponsor's protocol ID
- ASTX030-01
- Other IDs
- 2024-515098-93
- Status last verified
- Oct 2026
- First submitted
- 31 Jan 2020
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No