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Chronic Myelomonocytic LeukemiaPhase 2NCT05600894

Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 34 sites in 2 countries.

Active, not recruiting

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

Official record
Search all trials

Trial summary

This phase II trial tests whether decitabine and cedazuridine (ASTX727) in combination with venetoclax work better than ASTX727 alone at decreasing symptoms of bone marrow cancer in patients with chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with excess blasts. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
132 participants
Where
34 sitesin 2 countries
Study dates
27 Jun 2023to 31 Aug 2027
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

  • A diagnosis of an MDS/MPN "overlap" syndrome with >= 5% marrow blasts (including monocytic blast equivalent in case of CMML). Hydroxyurea may be used to control counts up until the start of therapy
  • White blood cell (WBC) < 25,000/mm^3. Treatment with hydroxyurea is permitted to lower the WBC to reach this criterion
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ASTX727 in combination with venetoclax in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless considered due to Gilbert's syndrome)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN OR =< 5.0 x institutional ULN for patients with liver metastases
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  • Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2
  • 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, they are eligible if they have an undetectable HCV viral load
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Hormonal therapy for prior or concurrent malignancy is allowed
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) and/or family member available will also be eligible
  • Ability to swallow pills

Who cannot join

  • Patients with need for emergent disease-directed therapy excluding hydroxyurea
  • More than one cycle of previous MDS/MPN-directed therapy, or MDS-directed therapy including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine, excluding hydroxyurea. Prior use of erythropoietin stimulating agents (ESA) and thrombopoietic agents is allowed, but must be discontinued 4 weeks prior to study treatment
  • Patients currently or previously receiving an investigational agent or device within 4 weeks of the first dose of treatment
  • Patients with symptomatic uncontrolled central nervous system (CNS) disease. Imaging to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
  • Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days prior to the initiation of study treatment and are unwilling to discontinue consumption of these throughout the receipt of study drug
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727 or venetoclax
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  • Patients with uncontrolled intercurrent illness (e.g. requiring intravenous therapy) at the discretion of the investigator
  • 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. Patients must be post-menopausal or with evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
  • Post-menopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50 years of age
  • Radiation-induced oophorectomy with last menses > 1 year ago
  • Chemotherapy-induced menopause with > 1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Women of child-bearing potential must agree to use adequate contraception (hormonal 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
  • Patients with any other medical condition for which the expected survival is below 12 months
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or assessment of the investigational regimen
  • Patients with uncontrolled infection at the time of study entry

Trial locations and contacts

34 sites in 2 countries.

34 sites in 2 countries

United States33 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, 92627

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

    Irvine, California, 92612

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • UCI Health Laguna Hills

    Laguna Hills, California, 92653

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Yale University

    New Haven, Connecticut, 06520

  • UC Comprehensive Cancer Center at Silver Cross

    New Lenox, Illinois, 60451

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • University of Chicago Medicine-Orland Park

    Orland Park, Illinois, 60462

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Venetoclax In Combination With ASTX727, an All-ORal TherapY for Chronic Myelomonocytic Leukemia and Other MDS/MPN With Excess Blasts (VICTORY-MDS/MPN): a Randomized, Phase 2 Trial

This phase II trial tests whether decitabine and cedazuridine (ASTX727) in combination with venetoclax work better than ASTX727 alone at decreasing symptoms of bone marrow cancer in patients with chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with excess blasts. Blasts are immature blood cells. 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 in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. The combination of ASTX727 and venetoclax may be more effective in reducing the cancer signs and symptoms in patients with CMML, or MDS/MPN with excess blasts.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the complete remission rates of ASTX727 and ASTX727 plus venetoclax in subjects with CMML and non-CMML MDS/MPN with excess (>= 5%) blasts.

SECONDARY OBJECTIVES:

  1. To evaluate the overall response rate (complete response [CR] + partial response [PR] + marrow response with erythroid response) of ASTX727 versus ASTX727 + venetoclax in this patient population.

II. To determine the overall survival, progression-free survival, allogeneic hematopoietic stem cell transplantation rate, clearance of the malignant clone, clonality at time of hematologic remission, number of red cell and platelet transfusions required and toxicity of ASTX727 versus ASTX727 + venetoclax.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (COMBINATION THERAPY): Patients receive ASTX727 orally (PO) once daily (QD) on days 1-5 of each cycle and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.

ARM II (MONO THERAPY): Patients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not have response to treatment may cross over to Arm I. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.

After completion of study treatment, patients are followed up every 6 months for 5 years or until death, whichever occurs first.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Decitabine and Cedazuridine, Venetoclax
Medical subject headings
Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Myelodysplastic-Myeloproliferative Diseases, Myeloproliferative Disorders

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 and buccal samples

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • 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 NCT05600894
Study groupRoleWhat they receive
Arm I (ASTX727, venetoclax)ExperimentalPatients receive ASTX727 PO QD on days 1-5 of each cycle and venetoclax PO QD on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Decitabine and Cedazuridine; Drug: Venetoclax
Arm II (ASTX727)Active comparatorPatients receive ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not have response to treatment may cross over to Arm I. Patients also undergo bone marrow biopsy and aspiration and collection of blood samples throughout the study and undergo buccal swab sample collection at screening.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Decitabine and Cedazuridine

What is being measured

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

  1. Complete response rate

    The complete remission rate will be compared between two arms using Fisher's exact test. Logistical regression will be used to estimate the effect of combination treatment on complete remission adjusting for covariates of interest.

    Measured: Up to 4 cycles

Secondary outcomes (3)

  1. Overall survival (OS)

    Will be calculated using the Kaplan-Meier method. Comparisons of OS between treatment arms will be conducted using the one-sided log-rank test. Hazard ratios will be computed using the Cox proportional hazards model. The censored follow-up time for patients without death information is the date of last contact.

    Measured: From randomization until death from any cause, assessed up to 5 years

  2. Progression-free survival (PFS)

    Will be calculated using the Kaplan-Meier method. Comparisons of PFS between treatment arms will be conducted using the one-sided log-rank test. Hazard ratios will be computed using the Cox proportional hazards model. For patients alive without progression, PFS will be censored at the date of the last disease evaluation.

    Measured: From randomization until disease progression or death from any cause, whichever comes first, assessed up to 5 years

  3. Incidence of adverse events

    An undesired effect of a drug or other type of treatment, such as surgery. Adverse events can range from mild to severe and can be life-threatening.

    Measured: Up to 5 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 Nov 2022
  2. Study start27 Jun 2023
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Aug 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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
132 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05600894
Sponsor's protocol ID
NCI-2022-08797
Other IDs
NCI-2022-08797, 10538, 10538, UM1CA186689
Status last verified
Aug 2026
First submitted
27 Oct 2022
Last updated
19 Aug 2026
Results posted
No
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 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome, run by National Cancer Institute (NCI) at 34 sites in 2 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 14 inclusion and 18 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 19 Aug 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, 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 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?

Complete response rate (time frame: Up to 4 cycles). 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 NCT05600894.

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 19 Aug 2026.

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