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Acute Myeloid LeukemiaPhase 1/2NCT04774393

Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1/2 study testing Decitabine and Cedazuridine, Enasidenib and Ivosidenib in people with Acute Myeloid Leukemia and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase Ib/II trials studies the side effects of decitabine/cedazuridine (ASTX727) and venetoclax in combination with ivosidenib or enasidenib, and how well they work in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Decitabine and Cedazuridine, Enasidenib and Ivosidenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
1 siteUnited States
Study dates
24 May 2021to 29 Nov 2027
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

  • Patients with a diagnosis of relapsed or refractory acute myeloid leukemia (AML) (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML); OR
  • Patients (> 60 year old) with newly diagnosed AML not eligible for intensive chemotherapy are also eligible
  • To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:
  • Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
  • Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second [FEV1] ≤65%).
  • Creatinine clearance ≥30 mL/min to <45 mL/min.
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  • Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0 × upper limit of normal (ULN)
  • ECOG performance status of 2 or 3
  • Age >= 18 years
  • Subjects must have documented IDH1 or IDH2 gene mutation
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Adequate renal function including creatinine < 2 unless related to the disease
  • Direct bilirubin < 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5 x ULN will be considered eligible)
  • In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy agent(s). Oral hydroxyurea and/or cytarabine (up to 2 g/m^2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principle investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
  • Male subjects who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug
  • Willing and able to provide informed consent

Who cannot join

  • Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)
  • Patients with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the patient at unacceptable risk of study treatment
  • Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI)
  • Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications
  • Corrected QT (QTc) interval using Fridericia's formula (QTcF) >= 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI
  • Known active hepatitis B (HBV) or hepatitis C (HCV) infection or known human immunodeficiency virus (HIV) infection
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  • Subject has a white blood cell count > 25 x 10^9/L. (Note: Hydroxyurea is permitted to meet this criterion)
  • Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception
  • Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Courtney DiNardo, MD contact

713-794-1141

cdinardo@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Courtney DiNardo, 713-794-1141, cdinardo@mdanderson.org

    Courtney DiNardo

    Recruiting

Other trials in United States

About this study

Official title: Phase 1b/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib

This phase Ib/II trials studies the side effects of decitabine/cedazuridine (ASTX727) and venetoclax in combination with ivosidenib or enasidenib, and how well they work in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). 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. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Enasidenib and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine/cedazuridine and venetoclax in combination with ivosidenib or enasidenib may help control acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety and tolerability and recommended phase 2 dose (RP2D) of oral decitabine/cedazuridine (ASTX727) and venetoclax in combination with either ivosidenib (Arm A) or enasidenib (Arm B) for patients with acute myeloid leukemia. (Phase Ib) II. To determine the overall response rate (complete response [CR], complete remission with incomplete hematologic recovery [CRh], morphologic leukemia-free state [MLFS] and partial response [PR)] of oral decitabine/cedazuridine (ASTX727) and venetoclax in combination with either ivosidenib (Arm A) or enasidenib (Arm B) for patients with acute myeloid leukemia. (Phase 2)

SECONDARY OBJECTIVES:

  1. To determine duration of response (DOR), event-free survival (EFS), and overall survival (OS).

II.To evaluate occurrence of minimal residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation.

III. To determine the overall response rate (CR, CRh, Cri, MLFS and PR)

IV. Characterize the pharmacokinetic (PK) profiles of venetoclax in plasma samples (Phase 1b only)

EXPLORATORY OBJECTIVE:

  1. To investigate global gene expression profiles, deoxyribonucleic acid (DNA) methylation profiles, BH3 profiling and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM A: Patients receive decitabine/cedazuridine orally (PO) daily on days 1-5, venetoclax PO daily on days 1-14, and ivosidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive decitabine/cedazuridine PO daily on days 1-5, venetoclax PO daily on days 1-14, and enasidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Decitabine and Cedazuridine, Enasidenib, Ivosidenib, 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

  • EnasidenibDrug

    Also called AG-221, CC-90007 Free Base

    Given PO

  • IvosidenibDrug

    Also called AG-120, Tibsovo

    Given PO

  • VenetoclaxDrug

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

    Given PO

Study groups in NCT04774393
Study groupRoleWhat they receive
Arm A (decitabine/cedazuridine, venetoclax, ivosidenib)ExperimentalPatients receive decitabine/cedazuridine PO daily on days 1-5, venetoclax PO daily on days 1-14, and ivosidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine and Cedazuridine; Drug: Ivosidenib; Drug: Venetoclax
Arm B (decitabine/cedazuridine, venetoclax, enasidenib)ExperimentalPatients receive decitabine/cedazuridine PO daily on days 1-5, venetoclax PO daily on days 1-14, and enasidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Decitabine and Cedazuridine; Drug: Enasidenib; Drug: Venetoclax

What is being measured

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

  1. Dose limiting toxicity (Phase Ib)

    Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 by organ system.

    Measured: Up to 1 cycle (1 cycle = 28 days)

  2. Overall response rate (ORR) (Phase II)

    Defined as complete remission (CR), CR with incomplete hematologic recovery, CR with incomplete count recovery, partial response or marrow clearance of blasts. Will estimate the ORR for the combination treatmen1t, along with the Bayesian 95% credible interval.

    Measured: Within 4 months of treatment

  3. Incidence of adverse events (Phase II)

    Assessed using Common Toxicity Criteria version 5.0. Safety data will be summarized using frequency and percentage, by category and severity.

    Measured: Within 4 months of treatment

Secondary outcomes (4)

  1. Event-free survival (EFS)

    The Kaplan-Meier method will be used to estimate the probabilities of EFS. Log-rank tests will be used to compare among subgroups of patients in terms of EFS.

    Measured: Time interval between treatment start until disease progression, relapse/refractory, or death due to any cause, assessed up to 3 years

  2. Overall survival (OS)

    The Kaplan-Meier method will be used to estimate the probabilities of OS. Log-rank tests will be used to compare among subgroups of patients in terms of OS.

    Measured: Time interval between treatment start until death due to any cause, assessed up to 3 years

  3. Duration of response

    The Kaplan-Meier method will be used to estimate the probabilities and log-rank tests will be used to compare among subgroups of patients.

    Measured: Up to 3 years

  4. Minimal residual disease negative status

    Will be summarized graphically and with descriptive statistics. The association between molecular and cellular markers and overall response and/or resistance will be assessed through logistic regression analyses. Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time.

    Measured: Up to 3 years

Timeline

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

  1. First posted1 Mar 2021
  2. Study start24 May 2021
  3. Primary completion29 Nov 2027 (estimated)
  4. Study completion29 Nov 2027 (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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
84 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04774393
Sponsor's protocol ID
2020-1220
Other IDs
NCI-2021-00893, 2020-1220
Status last verified
May 2026
First submitted
24 Feb 2021
Last updated
20 May 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • DiNardo CD, Marvin-Peek J, Loghavi S, Takahashi K, Issa GC, Jen WY, Daver NG, Reville PK, Short NJ, Sasaki K, Mullin JK, Bradley CA, Borthakur G, Maiti A, Alvarado Y, Pemmaraju N, Abbas HA, Hammond DE, Haddad F, Bravo GM, Chien KS, Yilmaz M, Kornblau SM, Jabbour E, Ravandi F, Kadia T, Garcia-Manero G, Konopleva MY, Kantarjian HM. Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML. J Clin Oncol. 2025 Aug 20;43(24):2692-2699. doi: 10.1200/JCO-25-00640. Epub 2025 Jun 13.

    PubMed 40513054

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Decitabine and Cedazuridine, Enasidenib and Ivosidenib 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 9 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: looking for participants now, as of the sponsor's last update on 20 May 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 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?

Contact Courtney DiNardo, MD (713-794-1141, cdinardo@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (Phase Ib) (time frame: Up to 1 cycle (1 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 NCT04774393, 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 20 May 2026.

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