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Acute Myeloid LeukemiaPhase 1/2NCT04657081

Pharmacokinetics, Safety, and Efficacy of ASTX727 in Combination With Venetoclax in Acute Myeloid Leukemia (AML)

A Phase 1/2 study testing Decitabine and Cedazuridine (ASTX727) and Venetoclax in people with Acute Myeloid Leukemia, run by Taiho Oncology, Inc. at 34 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The Phase 1 portion of this study is a single-arm, open-label, multicenter, non-randomized interventional study to evaluate the pharmacokinetic (PK) interaction, safety, and efficacy of ASTX727 when given in combination with venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Decitabine and Cedazuridine (ASTX727) and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
34 sitesin 3 countries
Study dates
9 Feb 2021to 31 Dec 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Participant must be 18 years of age or older.
  • Histological confirmation of newly diagnosed AML by World Health Organization (WHO) 2016 criteria.
  • Projected life expectancy of at least 3 months.
  • Participants must be considered ineligible for intensive induction chemotherapy defined by the following: a) Age 75 years or older, or b) Age 18 to 74 years with at least one of the following comorbidities: i) Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina), ii) Severe pulmonary disorder (eg, diffusing lung capacity 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), v) Phase 1: Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 (participants with ECOG ≥3 are not eligible); Phase 2, Parts A and B: ECOG Performance Status of 2 or 3 (participants with ECOG 4 are not eligible).
  • Phase 1: ECOG Performance Status of 0-2; Phase 2, Parts A and B: ECOG 0-3.
  • 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.
  • Participants and their partners with reproductive potential must agree to use a highly effective contraceptive measure during the study and for 3 months after the last dose of study treatment, including refraining from sperm donation. Effective contraception includes methods such as oral contraceptives or double-barrier method (eg, use of a condom AND diaphragm, with spermicide).
  • Capable of giving legally effective informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and protocol, and willing to participate in the study.

Who cannot join

  • History of myeloproliferative neoplasm including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
  • The following karyotype abnormalities: t(8;21), inv(16) or t(15;17), or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy.
  • Known active central nervous system involvement from AML.
  • Known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). Human immunodeficiency virus testing will be performed at Screening, only if indicated per local guidelines or institutional standards.
  • Known active hepatitis B or C infection (detectable viral load). Hepatitis B or C testing will be performed at Screening, only if indicated per local guidelines or institutional standards.
  • Severe hepatic impairment defined as: bilirubin >1.5×upper limit of normal (ULN) for participants ≥75 years or >3×ULN for participants <75 years; or aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) >3×ULN (unless considered to be due to leukemic organ involvement).
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  • Severe renal impairment defined as: calculated creatinine clearance or glomerular filtration rate <30 mL/min.
  • A malabsorption syndrome or other condition that precludes enteral route of administration.
  • Cardiovascular disability status of New York Heart Association Class >2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
  • Chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications that in the opinion of the investigator would adversely affect his/her participating in this study.
  • Clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
  • 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.
  • White blood cell (WBC) count >25,000/μL (Hydroxyurea treatment is permitted to meet this criterion).
  • Treatment with the following: a) A hypomethylating agent (azacitidine or decitabine), or venetoclax including prior treatment for myelodysplastic syndrome (MDS), b) Chimeric Antigen Receptor (CAR)-T cell therapy, c) Investigational therapies for MDS or AML.
  • Participants who cannot discontinue concomitant prophylactic antifungal therapy with CYP3A inhibitor activity or other concomitant medications with moderate or strong CYP3A inhibitor activity ≥7 days or 5 half-lives, whichever is greater, prior to cycle 1 day 1 (C1D1).
  • Participants who cannot discontinue concomitant drugs that are strong CYP3A or P-gp inhibitors ≥7 days or 5 half-lives, whichever is greater, prior to C1D1.
  • Participants who cannot avoid concomitant drugs known as moderate or strong CYP3A inducers.
  • Current participation in another research study requiring interventions such as drug therapy or study procedures.
  • Known or suspected hypersensitivity to decitabine, cedazuridine, venetoclax, or any of their excipients.
  • 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 participant to high risk of noncompliance with the protocol.
  • Participants who consume grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit ≤7 days prior to C1D1.

Trial locations and contacts

34 sites in 3 countries.

34 sites in 3 countries

United States24 sites

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • The Ohio State University

    Columbus, Ohio, 43210

  • East Carolina University

    Greenville, North Carolina, 27834

  • Hackensack University of Medical Center

    Hackensack, New Jersey, 07601

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Health Midwest Ventures Group, Inc.

    Kansas City, Missouri, 64132

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-6307

  • Yale University

    New Haven, Connecticut, 06510

  • Weill Cornell Medical College

    New York, New York, 10065

  • Stanford University

    Palo Alto, California, 94306

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Boca Raton Clinical Research

    Plantation, Florida, 33322

  • University of Rochester

    Rochester, New York, 14627

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • The Research Foundation of the State University of New York (SUNY)

    Syracuse, New York, 13210

  • Baylor Scott & White Research Institute

    Temple, Texas, 76508

  • University of Massachusetts, Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

Spain6 sites

  • Institut Catala d'Oncologia-Hospital Duran i Reynals

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario Central de Asturias

    Oviedo, Austrias, 33011

  • Clinica Universidad de Navarra, Pamplona

    Pamplona, Navarre, 31008

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

Other trials in Spain

Canada4 sites

  • University of Calgary - Health Sciences Centre

    Calgary, Alberta, T2N 4N1

  • University of Alberta

    Edmonton, Alberta, T6G 2R3

  • Jewish General Hospital

    Montreal, H3T 1E2

  • The Ottawa Hospital, General Campus

    Ottawa, Ontario, K1H 8L6

Other trials in Canada

About this study

Official title: A Single-Arm, Open-Label Pharmacokinetic, Safety, and Efficacy Study of ASTX727 in Combination With Venetoclax in Adult Patients With Acute Myeloid Leukemia

The Phase 1 portion of this study is a single-arm, open-label, multicenter, non-randomized interventional study to evaluate the pharmacokinetic (PK) interaction, safety, and efficacy of ASTX727 when given in combination with venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. The primary purpose of the study is to rule out drug-drug interactions between ASTX727 and venetoclax combination therapy by evaluating area under the curve (AUC) and maximum plasma concentration (Cmax) exposure. The Phase 2 portion of the study is to assess the efficacy of ASTX727 and venetoclax when given in combination and to evaluate potential PK interactions. Phase 2 will follow the same overall study design as Phase 1 and has two parts, Part A and Part B. Following study completion, participants who get clinical benefit without unnecessary risks may continue to receive study treatment in the study extension phase.

Being tested
Decitabine and Cedazuridine (ASTX727), Venetoclax
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Decitabine and Cedazuridine (ASTX727)Drug

    Also called INQOVI

    Route of administration: oral in the form of a tablet

  • VenetoclaxDrug

    Also called Venclexta

    Route of administration: oral in the form of a tablet

Study groups in NCT04657081
Study groupRoleWhat they receive
Oral administration of ASTX727 and Venetoclax combinationExperimentalCycle 1: ASTX727 according to a prescribed dosing regimen and venetoclax on day 1 (100 mg daily), day 2 (200 mg daily), and days 3-28 (400 mg daily) of a 28-day cycle. Cycle 2 and beyond: ASTX727 according to a prescribed dosing regimen and venetoclax on days 1-28 (400 mg daily) of a 28-day cycle.
Receives: Drug: Decitabine and Cedazuridine (ASTX727); Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetic Parameter: AUC0-24

    Venetoclax area under the curve from time 0 to 24 hours (AUC0-24) with and without ASTX727 in Phase 1 and Phase 2, Part A.

    Measured: On Days 5 and 15 in Cycle 2 (28 days per cycle)

  2. Pharmacokinetic Parameter: Cmax

    Venetoclax maximum observed concentration (Cmax) with and without ASTX727 in Phase 1 and Phase 2, Part A.

    Measured: On Days 5 and 15 in Cycle 2 (28 days per cycle)

  3. Complete Response (CR)

    Number of participants with CR in Phase 2, Parts A and B.

    Measured: Up to 36 months

Secondary outcomes (13)

  1. Pharmacokinetic Parameter: AUC0-24

    Decitabine and cedazuridine area under the curve from time 0 to 24 hours (AUC0-24) in Phase 1 and Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

  2. Pharmacokinetic Parameter: Cmax

    Decitabine and cedazuridine maximum observed concentration (Cmax) in Phase 1 and Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

  3. Pharmacokinetic Parameter: AUC0-8

    Decitabine and cedazuridine area under the curve from time 0 to 8 hours (AUC0-8) in Phase 1 and Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

  4. Pharmacokinetic Parameter: AUC0-inf

    Decitabine and cedazuridine area under the curve from time 0 to infinity (AUC0-inf) in Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

  5. Pharmacokinetic Parameter: 5-day AUC

    Decitabine 5-day cumulative AUC in Phase 1.

    Measured: Cycle 2 (28 days per cycle)

  6. Safety: Participants with TEAEs

    Number of participants with treatment-emergent adverse events (TEAEs) in Phase 1 and Phase 2, Parts A and B.

    Measured: Up to 36 months

  7. Complete response (CR)

    Number of participants with CR (Phase 1), CR + complete response with partial hematological recovery (CRh), and CR + incomplete blood count recovery (CRi) in Phase 1 and 2, Parts A and B.

    Measured: Up to 36 months

  8. Time to Response

    Number of days from the first dose to the first documented evidence of complete response or CRh in Phase 1 and Phase 2, Parts A and B.

    Measured: Up to 36 months

  9. Duration of Response

    Number of days from the start of response (CR or CRh) until disease progression, start of alternative antileukemia therapy, or death in Phase 1 and Phase 2, Parts A and B.

    Measured: Up to 36 months

  10. Overall Survival

    Number of days from date of first dose until death due to any cause in Phase 1 and Phase 2, Parts A and B.

    Measured: Up to 36 months

  11. Pharmacokinetic parameter: Cmin

    Venetoclax, decitabine and cedazuridine minimum observed concentration (Cmin) in Phase 1 and Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

  12. Pharmacokinetic parameter: Tmax

    Venetoclax, decitabine and cedazuridine time to maximum observed concentration in Phase 1 and Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

  13. Pharmacokinetic Parameter: Apparent Elimination Half-life (T1/2)

    Venetoclax, decitabine and cedazuridine T1/2 in Phase 1 and Phase 2, Parts A and B.

    Measured: Cycles 1, 2 and 3 (28 days per cycle)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2020
  2. Study start9 Feb 2021
  3. Primary completion30 Sep 2024
  4. Study completion31 Dec 2028 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04657081
Sponsor's protocol ID
ASTX727-07
Other IDs
2024-516294-78-00
Status last verified
Oct 2026
First submitted
1 Dec 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

Publications

  • Roboz GJ, Zeidan AM, Mannis GN, Montesinos P, Arnan M, Savona MR, Odenike O, McCloskey JK, Amin HV, Fathi AT, Bernal Del Castillo T, Rodriguez-Macias G, Liesveld JL, Im AP, Cerny J, Gentile TC, Oganesian A, Chan D, Wan Y, Dijkstra M, Keer HN, Griffiths EA, DiNardo CD. All-Oral Treatment of Newly Diagnosed Acute Myeloid Leukemia. N Engl J Med. 2026 Jun 4;394(21):2107-2116. doi: 10.1056/NEJMoa2510223.

    PubMed 42235013

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Decitabine and Cedazuridine (ASTX727) and Venetoclax in people with Acute Myeloid Leukemia, run by Taiho Oncology, Inc. at 34 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in United States, Spain, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic Parameter: AUC0-24 (time frame: On Days 5 and 15 in Cycle 2 (28 days per cycle)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04657081, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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