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Acute Myeloid LeukemiaPhase 2NCT04746235

Venetoclax and ASTX727 for the Treatment of Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia

A Phase 2 study testing Decitabine and Cedazuridine and Venetoclax in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 II trial studies the possible benefits of venetoclax and ASTX727 in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or elderly patients with newly diagnosed acute myeloid leukemia who are not candidates for intensive chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Decitabine and Cedazuridine and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
1 siteUnited States
Study dates
22 Feb 2021to 31 Oct 2028
Phase
Phase 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

  • Patients with AML by the World Health Organization (WHO) classification who have failed prior therapy, refractory to it or relapsed after prior response. Patients with isolated extramedullary AML are eligible (cohort 1)
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • For cohort 2 (frontline elderly or unfit AML AML), the following inclusion criteria:
  • Confirmed newly diagnosed AML
  • Ineligible for induction therapy defined as
Show all 17Show fewer
  • Either age >= 75 years
  • Or 18-74 years of age with at least one comorbidity (chronic heart failure [CHF] requiring therapy or eject fraction [EF] =< 50%, carbon monoxide diffusing capability [DLCO] =< 65% or forced expiratory volume in 1 second [FEV1] =< 65%, or ECOG 2 or 3)
  • Creatinine clearance ≥30 mL/min to <45 mL/min
  • Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0 × upper limit of normal (ULN)
  • Creatinine clearance ≥ 45 ml/min unless related to the disease (e.g. infiltration)
  • Total bilirubin < 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
  • Alanine aminotransferase (ALT) < 3 x ULN unless considered due to leukemic involvement (by biopsy or imaging)
  • Able to give written informed consent
  • Oral hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and hydroxyurea while the patient is on active study treatment through cycle 1, as needed, for clinical benefit and after discussion with the principal investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
  • Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
  • Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

Who cannot join

  • Acute promyelocytic leukemia
  • Prior therapy with a BCL2 inhibitor
  • Symptomatic or uncontrolled CNS leukemia
  • Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
  • Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
  • Pregnant or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 2 Study of Venetoclax in Combination With ASTX727 in Patients With Relapsed/Refractory Acute Myeloid Leukemia, and Newly Diagnosed Elderly Patients With AML Who Are Not Candidates for Intensive Chemotherapy

This phase II trial studies the possible benefits of venetoclax and ASTX727 in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or elderly patients with newly diagnosed acute myeloid leukemia who are not candidates for intensive chemotherapy. Venetoclax may help block the formation of growths that may become cancer. ASTX727 is the combination of a fixed dose of 2 drugs, cedazuridine and decitabine. Cedazuridine may slow down how fast decitabine is broken down by the body, and decitabine may block abnormal cells or cancer cells from growing. Giving venetoclax and ASTX727 may help to control the disease.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the overall response rate (ORR) of decitabine and cedazuridine (ASTX727) in combination with venetoclax in patients with refractory/relapsed acute myeloid leukemia (AML).

II. To determine the overall response rate (ORR) of ASTX727 in combination with venetoclax in elderly ((≥ 75 years or ≥ 18 years with comorbidities) patients with newly diagnosed acute myeloid leukemia (AML) not eligible for intensive chemotherapy.

SECONDARY OBJECTIVES:

  1. To determine the duration of response, disease-free survival (DFS), and overall survival (OS) of patients with refractory/relapsed AML treated with this combination.

II. To determine similar outcomes for newly diagnosed patients with AML who are not candidates for intensive chemotherapy.

III. To determine the safety of venetoclax in combination with ASTX727 in patients with refractory/ relapsed AML, and newly diagnosed patients with AML not candidates for intensive chemotherapy.

IV. To determine the number of relapsed patients able to proceed to stem cell transplantation upon achieving response with the combination venetoclax/ASTX727 regimen.

EXPLORATORY OBJECTIVE:

  1. To characterize the pharmacokinetic (PK) profiles of ASTX727 when combined with venetoclax.

OUTLINE:

Patients receive decitabine and cedazuridine orally (PO) daily on days 1-5 and venetoclax PO daily on days 1-28 of the first cycle and on days 1-21 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients with an objective response are followed every 3-6 months for up to 5 years.

Being tested
Decitabine and Cedazuridine, 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 CedazuridineDrug

    Also called ASTX727, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet

    Given PO

  • VenetoclaxDrug

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

    Given PO

Study groups in NCT04746235
Study groupRoleWhat they receive
Treatment (decitabine and cedazuridine, venetoclax)ExperimentalPatients receive decitabine and cedazuridine PO daily on days 1-5 and venetoclax PO daily on days 1-28 of the first cycle and on days 1-21 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine and Cedazuridine; Drug: Venetoclax

What is being measured

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

  1. Overall response rate (ORR)

    Will be defined as the proportion of patients who had CR (complete remission), CRp (complete remission with incomplete platelet recovery), CRi (complete remission with incomplete count recovery), PR (partial response) or marrow clearance of blasts within 3 months of treatment initiation among adult patients with acute myeloid leukemia (AML). Response criteria will be modified from the International Working Group for AML. Will estimate the ORR for the combination treatments for each cohort, along with the 90% credible intervals. The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

    Measured: Within 3 months of treatment initiation

  2. Overall incidence and severity of all adverse events

    Will be assessed by Common Toxicity Criteria version 5.0.

    Measured: Up to 5 years post treatment

Secondary outcomes (2)

  1. Disease free survival

    Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

    Measured: Up to 5 years post treatment

  2. Overall survival

    Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

    Measured: Up to 5 years post treatment

Timeline

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

  1. First posted9 Feb 2021
  2. Study start22 Feb 2021
  3. Primary completion31 Oct 2028 (estimated)
  4. Study completion31 Oct 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04746235
Sponsor's protocol ID
2020-1007
Other IDs
NCI-2021-00112, 2020-1007
Status last verified
Oct 2026
First submitted
1 Feb 2021
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bazinet A, Garcia-Manero G, Short N, Alvarado Y, Bataller A, Abuasab T, Islam R, Montalbano K, Issa G, Maiti A, Yilmaz M, Jain N, Masarova L, Kornblau S, Jabbour E, Montalban-Bravo G, Rausch CR, Pierce S, DiNardo CD, Kadia T, Daver N, Konopleva M, Huang X, Kantarjian H, Ravandi F. Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia: a phase 2 study. Lancet Haematol. 2024 Apr;11(4):e276-e286. doi: 10.1016/S2352-3026(24)00033-4. Epub 2024 Mar 4.

    PubMed 38452788

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Decitabine and Cedazuridine and Venetoclax in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 17 inclusion and 6 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 5 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 1 site 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 phase mean?

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?

Overall response rate (ORR) (time frame: Within 3 months of treatment initiation). The study lists 2 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 NCT04746235, 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 5 Oct 2026.

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