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Acute Myeloid LeukemiaPhase 1/2NCT04817241

Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients

A Phase 1/2 study testing Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Cytarabine in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 7 sites in United States.

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

This phase Ib/II trial studies the effects of ASTX727 (decitabine and cedazuridine) in combination with venetoclax in treating patients with higher-risk acute myeloid leukemia patients who do not have a change in the gene called fms-like tyrosine kinase 3 (FLT3). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
7 sitesUnited States
Study dates
10 Feb 2022to 5 Nov 2026
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must be between 18-65 years of age at the time of signing the Informed Consent Form (ICF) and must be able to meet all study requirements. AML patients under the age of 18 are excluded as is being studied in patients under 18 years of age in different venues
  • Morphologically confirmed diagnosis of AML in accordance with World Health Organization (WHO) diagnostic criteria
  • Adverse risk AML per 2017 European LeukemiaNet (ELN) recommendations
  • Subjects must be either treatment naive defined by =< 1 cycle of deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) therapy, no history of cytotoxic chemotherapy for their AML; prior treatment with lenalidomide, hydroxyurea or erythropoiesis-stimulating agents (ESAs) is allowed (prior treatment for myelodysplastic syndrome [MDS] with > 1 cycle of DNMTi is not allowed)
  • A bone marrow aspirate and biopsy must be performed, and tissue collected for entrance to the trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
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  • Recovery to =< grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia
  • White blood cell count (WBC) < 25,000 (may be reduced with leukapheresis or hydroxyurea prior to study start)
  • Direct bilirubin =< 2 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN
  • Creatinine clearance >= 30 mL/min (per the Cockcroft-Gault formula)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment or have received treatment, they are eligible if they have an undetectable HCV viral load
  • Tumor lysis present prior to therapy must be treated accordingly prior to start of therapy
  • The effects of venetoclax and ASTX727 on the developing human fetus are unknown. For this reason and because BCL2 inhibitor and DNMTi agents as well as other therapeutic agents used in this trial (cytarabine and daunorubicin) are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal method of birth control or abstinence) prior to study entry and for the duration of study participation, and for 6 months following completion of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception (latex or synthetic condom or abstinence) prior to the study, for the duration of study participation, and 3 months after completion of venetoclax and ASTX727 administration
  • Ability to understand and the willingness to sign a written informed consent document
  • Adequate cardiac systolic function as measured by ejection fraction (EF) >= 50%

Who cannot join

  • Favorable or intermediate risk AML as defined by 2017 ELN criteria
  • Presence of FLT3 TKD or FLT-ITD mutations
  • Inability to tolerate oral medication or keep a pill diary
  • Active documented central nervous system (CNS) leukemia
  • Concurrent treatment with a non-permitted concomitant medication
  • Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment
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  • Other malignancy currently being treated or likely to be treated in next 6 months with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ and patients receiving hormonal therapy for prevention of hormone-sensitive cancers
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax, ASTX727, or other agents used in study
  • Patient must not have received known moderate or strong CYP3A inducers within 7 days of enrollment. Patient must not have known medical conditions requiring chronic therapy of moderate CYP3A inducers. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Patients with uncontrolled intercurrent illness
  • Patients with psychiatric illness/social situations (including substance abuse) that would limit compliance with study requirements
  • Pregnant women are excluded from this study because venetoclax and ASTX727 have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax. These potential risks may also apply to other agents used in this study
  • Previous exposure to either venetoclax or > 1 cycle of DNMTi (e.g. azacitidine, decitabine, ASTX727, CC486)
  • Active, uncontrolled infection as determined by the investigator. Patients with infection under active treatment and controlled with antibiotics are eligible
  • Any condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: Clinical Evaluation of ASTX727 in Combination With Venetoclax All-Oral Therapy vs Standard of Care Cytarabine and Anthracycline Induction Chemotherapy for Younger FLT3WT Patients With ELN High- Risk Acute Myeloid Leukemia

This phase Ib/II trial studies the effects of ASTX727 (decitabine and cedazuridine) in combination with venetoclax in treating patients with higher-risk acute myeloid leukemia patients who do not have a change in the gene called fms-like tyrosine kinase 3 (FLT3). Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is an enzyme inhibitor. It helps to increase the amount of decitabine in the body so that the medication will have a greater effect. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Venetoclax and decitabine are commonly given together for older patients with AML ASTX727 (a pill form of decitabine + cedazuridine) has been found to be equal to decitabine (given intravenously), and this part of the study is to confirm that venetoclax and ASTX727 is as safe as venetoclax and decitabine given intravenously. This study allows for lowering doses of study drugs to assure the dose chosen for the randomized study (second portion of this trial) is safe and tolerable for people. Giving ASTX727 in combination with venetoclax may help in the treatment of patients with higher-risk acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine and compare the preliminary efficacy of venetoclax +ASTX727 versus (vs.) standard anthracycline induction therapy ('7+3') with a primary endpoint of event-free survival (EFS).

SECONDARY OBJECTIVES:

  1. To determine the complete response (complete response [CR] + complete response with incomplete bone marrow recovery [CRi]) rate in patients with treatment naive FLT3 wild type (WT) acute myeloid leukemia (AML) treated with venetoclax and ASTX727 vs. standard anthracycline induction therapy ('7+3').

II. To determine the duration of response (DoR) in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs. standard anthracycline induction therapy ('7+3').

III. To determine the progression free survival (PFS) of patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs. standard anthracycline induction therapy ('7+3').

IV. To determine the overall response rate (ORR) in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs. standard anthracycline induction therapy ('7+3').

  1. To determine the overall survival (OS) of patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs. standard anthracycline induction therapy ('7+3').

VI. To determine the proportion of patients receiving stem cell transplantation (SCT) in patients with treatment naive FLT3WT AML treated with venetoclax and ASTX727 vs. standard anthracycline induction therapy ('7+3').

VII. To identify mutational burdens in venetoclax +ASTX727 sensitive vs. resistant AML leukemia initiating cells (LICs).

EXPLORATORY OBJECTIVES:

  1. To identify transcriptomic signatures in venetoclax +ASTX727 sensitive vs. resistant AML LICs.

II. Determine the utility of high-throughput phenotype-based assessment of drug efficacy for predicting patient response to venetoclax +ASTX727.

III. Determine if treatment failure is a function of therapy sequence or results in resistance to the alternative therapy by conducting a co-clinical trial via patient-derived xenograft (PDX).

IV. To characterize the pharmacokinetics of venetoclax. V. To determine the morphologic leukemia-free state (MLFS) rate in patients with treatment naïve FLT3WT AML treated with venetoclax and ASTX727 vs. 7+3 therapy.

OUTLINE: This is a phase Ib dose de-escalation study followed by a phase II randomized study.

PHASE Ib: Patients receive ASTX727 (decitabine and cedazuridine) orally (PO) once daily (QD) on days 1-4 or 1-5 of each cycle and venetoclax PO QD on days 1-28 or days 1-21 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ASTX727 PO QD at the recommended phase II dose and venetoclax PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial.

ARM II: Patients receive cytarabine intravenously (IV) over 24 hours on days 1-7 of each cycle and daunorubicin IV over 10-30 minutes on days 1-3 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy throughout the trial.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Being tested
Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Cytarabine, Daunorubicin, Decitabine and Cedazuridine
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.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • DaunorubicinDrug

    Also called Daunomycin, Daunorrubicina, DNR, Leukaemomycin C

    Given IV

  • Decitabine and CedazuridineDrug

    Also called ASTX 727, ASTX-727, ASTX727, C-DEC

    Given PO

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

Study groups in NCT04817241
Study groupRoleWhat they receive
Arm I (decitabine and cedazuridine, venetoclax)ExperimentalPatients receive ASTX727 PO QD at the recommended phase II dose and venetoclax PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Decitabine and Cedazuridine; Drug: Venetoclax
Arm II (cytarabine, daunorubicin)Active comparatorPatients receive cytarabine IV over 24 hours on days 1-7 of each cycle and daunorubicin IV over 10-30 minutes on days 1-3 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy throughout the trial.
Receives: Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cytarabine; Drug: Daunorubicin
Phase Ib (decitabine and cedazuridine, venetoclax)ExperimentalPatients receive ASTX727 PO QD on days 1-4 or 1-5 of each cycle and venetoclax PO QD on days 1-28 or days 1-21 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy and collection of blood samples throughout the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Decitabine and Cedazuridine; Drug: Venetoclax

What is being measured

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

  1. Recommended Safe Phase 2 Dose (RP2D) of Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax (Phase Ib)

    The highest dose level in which at most 1 patient in 6 experiences dose-limiting toxicity (DLT).

    Measured: From start of treatment to end of first cycle (28 days)

  2. Incidence of Adverse Events (Phase Ib)

    Will be tabulated and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Summary statistics will be provided for all adverse events reported. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percent and frequencies for categorical parameters, will be presented

    Measured: Adverse event data were collected for the first five days of treatment, weekly for the next three weeks, and then day 1 of each subsequent 4-week cycle during treatment, and up to 35 days following completion of treatment.

  3. Event-free Survival (EFS) (Phase II)

    Will be estimated using the method of Kaplan and Meier and compared among treatments and other important prognostic groups using the log-rank test. EFS is defined as survival without death, blasts>20%, myeloid sarcoma, or AML in the central nervous system (CNS disease).

    Measured: Up to 2 years after completion of study treatment

Secondary outcomes (7)

  1. Complete Response Rate (Phase II)

    Rate of complete response (CR) + complete response with incomplete bone marrow recovery (CRi). The ELN criteria was used for definitions of response: CR, Complete Remission; CRi, Complete Remission with Incomplete Blood Count Recovery.

    Measured: Up to 2 years after completion of study treatment

  2. Duration of Response (Phase II)

    Will be estimated using the method of Kaplan and Meier and compared among treatments and other important prognostic groups using the log-rank test. The ELN criteria was used for definitions of response: CR, Complete Remission; CRi, Complete Remission with Incomplete Blood Count Recovery, PR: partial remission.

    Measured: Up to 2 years after completion of study treatment

  3. Progression-free Survival (PFS) (Phase II)

    The distribution of PFS will be estimated using the method of Kaplan and Meier. Hazard rate for PFS will be estimated, along with 95% confidence intervals, using the Cox (proportional hazards) regression model.

    Measured: Time from randomization date to the date of progression or death for any reason, assessed up to 2 years after completion of study treatment

  4. Overall Response Rate (Phase II)

    Rate of partial response (PR) + CRi + CR in patients with treatment naive AML treated with venetoclax and ASTX727. The ELN criteria was used for definitions of response: CR, Complete Remission; CRi, Complete Remission with Incomplete Blood Count Recovery, PR: partial remission.

    Measured: Up to 2 years after completion of study treatment

  5. Overall Survival (OS) (Phase II)

    The distribution of OS will be estimated using the method of Kaplan and Meier. Hazard rate for OS will be estimated, along with 95% confidence intervals, using the Cox (proportional hazards) regression model.

    Measured: Time from randomization to death for any reason, assessed up to 2 years after completion of study treatment

  6. The Proportion of Treatment Naive AML Patients Receiving Stem Cell Transplantation (SCT) Following Treatment With Venetoclax and ASTX727 (Phase II)

    Measured: Up to 2 years after completion of study treatment

  7. Mutational Burdens in Venetoclax + ASTX727 Sensitive vs. Resistant AML Leukemia Initiating Cells (LICs) (Phase II)

    Measured: Up to 2 years after completion of study treatment

Timeline

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

  1. First posted26 Mar 2021
  2. Study start10 Feb 2022
  3. Primary completion6 Jun 2025
  4. Study completion5 Nov 2026 (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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04817241
Sponsor's protocol ID
NCI-2021-02246
Other IDs
NCI-2021-02246, VICCNCIHEM10417, 10417, 10417, UM1CA186689
Status last verified
May 2026
First submitted
25 Mar 2021
Last updated
3 Nov 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Cytarabine in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI) at 7 sites in United States.

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 18 inclusion and 15 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 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. 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?

Yes. Results are posted in the registry (first posted 6 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Recommended Safe Phase 2 Dose (RP2D) of Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax (Phase Ib) (time frame: From start of treatment to end of first cycle (28 days)). 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 NCT04817241.

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 3 Nov 2026.

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