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Chronic Myelomonocytic LeukemiaPhase 1/2NCT04655755

Venetoclax in Combination With ASTX727 for the Treatment of Treatment-Naive High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

A Phase 1/2 study testing Decitabine and Cedazuridine and Venetoclax in people with Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome, 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 I/II trial studies the side effects and best dose of venetoclax in combination with cedazuridine and decitabine (ASTX727) in treating patients with high risk myelodysplastic syndrome or chronic myelomonocytic leukemia who have not received prior treatment (treatment-naive). 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
52 participants
Where
1 siteUnited States
Study dates
19 Jan 2021to 20 Jul 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

  • Patients with treatment-naive high-risk (HR)-MDS or CMML (intermediate [Int]-2 or high risk by the International Prognostic Scoring System [IPSS] with overall score >= 1.5) with excess blasts > 5. Note: Patients with therapy-related MDS are eligible. Hydroxyurea is allowed to lower the white cell count =< 10,000/ul prior to initiation of venetoclax
  • Total bilirubin < 3 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3.0 x ULN unless considered due to leukemic involvement
  • Creatinine < 2 x ULN unless related to the disease
  • Signed written informed consent
  • 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
  • Age >= 18 years of age

Who cannot join

  • Patients having received any prior BCL2 inhibitor therapy
  • Patients with MDS with IPSS risk categories low or Int-1 (overall IPSS score < 1.5)
  • Patient with known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). HIV testing will be performed at screening, only if required per local guidelines or institutional standards
  • Patient known to be positive for hepatitis B or C infection (hepatitis C virus antibody [HCV Ab] indicative of a previous or current infection; and/or positive hepatitis B surface antigen [HBs Ag] or detected sensitivity on hepatitis B virus-deoxyribonucleic acid [HBV-DNA] polymerase chain reaction [PCR] test for hepatis B core antibody [HBc Ab] and/or HBs Ab positivity) with the exception of those with an undetectable viral load within 3 months of screening. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate
  • Patient has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment
  • Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment
Show all 17Show fewer
  • Patient has a 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
  • Patient has 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 including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study
  • Patient has a malabsorption syndrome or other condition that precludes enteral route of administration
  • Patient exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal)
  • Patient has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug
  • Patient has a history of other malignancies within 2 years prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD
  • Patient has a white blood cell count > 25 x 10^9/L. (Hydroxyurea or leukapheresis are permitted to meet this criterion)
  • Female subject has positive results for pregnancy test

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 I/II Study of Venetoclax in Combination With ASTX727 (Cedazuridine/Decitabine) in Treatment-Naïve High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

This phase I/II trial studies the side effects and best dose of venetoclax in combination with cedazuridine and decitabine (ASTX727) in treating patients with high risk myelodysplastic syndrome or chronic myelomonocytic leukemia who have not received prior treatment (treatment-naive). Chemotherapy drugs, such as venetoclax, cedazuridine, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the safety and tolerability (phase 1) and overall response rate (ORR) (phase 2) of venetoclax in combination with ASTX727 in patients with treatment-naive high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with bone marrow excess blasts > 5%.

SECONDARY OBJECTIVES:

  1. Rate of complete remission (CR). II. Rate of marrow/morphologic complete remission (mCR). III. Rate of hematologic improvement (HI; erythroid/platelet/neutrophil responses).

IV. Rate of red blood cell (RBC) transfusion independence. V. Rate of platelet (PLT) transfusion independence. VI. Rate of cytogenetic response. VII. Rate of bone marrow blast response. VIII. Time to transformation to acute myeloid leukemia (AML). IX. Duration of response (DOR). X. Overall survival (OS). XI. Progression-free survival (PFS). XII. Disease-free survival (DFS). XIII. Time to next MDS treatment (TTNT). XIV. Event-free survival (EFS).

EXPLORATORY OBJECTIVE:

  1. To investigate the effects of therapy on MDS and to identify biological markers of response to venetoclax and/or its combination with ASTX727.

OUTLINE: This is a phase I, dose-escalation study of venetoclax, followed by a phase II study.

Patients receive venetoclax orally (PO) once daily (QD) on days 1-14. Patients also receive ASTX727 PO QD on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Being tested
Decitabine and Cedazuridine, Venetoclax
Medical subject headings
Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes

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 NCT04655755
Study groupRoleWhat they receive
Treatment (venetoclax, ASTX727)ExperimentalPatients receive venetoclax orally PO QD on days 1-14. Patients also receive ASTX727 PO QD on days 1-5. Cycles repeat every 28 days 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. Incidence and severity of all reported adverse events (Phase I)

    The overall incidence and severity of all reported adverse events using Common Toxicity Criteria version 5.0.

    Measured: Up to 28 days

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

    ORR will be defined as the proportion of patients who had complete remission (CR), partial remission (PR) or marrow CR (mCR), or hematologic improvement (HI) lasting at least 8 weeks. Will estimate the ORR for the combination treatment, along with the 95% credible interval.

    Measured: Up to 8 weeks

Secondary outcomes (14)

  1. Rate of complete remission

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  2. Rate of marrow/morphologic complete remission

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  3. Rate of hematologic improvement (HI; erythroid/platelet/neutrophil responses)

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  4. Rate of red blood cell transfusion independence

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  5. Rate of platelet transfusion independence

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  6. Rate of cytogenetic response

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  7. Rate of bone marrow blast response

    Will be estimated with the 95% credible interval.

    Measured: Up to 5 years post treatment

  8. Duration of response

    Measured: From the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first, assessed up to 5 years

  9. Time to transformation to acute myeloid leukemia

    Time to transformation to acute myeloid leukemia is defined as the period from treatment till transformed to acute myeloid leukemia.

    Measured: Up to 5 years post treatment

  10. Overall survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From treatment start till death, assessed up to 5 years

  11. Progression-free survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From treatment start till disease progression or death, assessed up to 5 years

  12. Disease-free survival

    Measured: Up to 5 years post treatment

  13. Time to next myelodysplastic syndrome (MDS) treatment

    Will be estimated using the method of Kaplan and Meier.

    Measured: From initial treatment start till the next MDS treatment, assessed up to 5 years

  14. Event-free survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From treatment initiation to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first, assessed 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 posted7 Dec 2020
  2. Study start19 Jan 2021
  3. Primary completion20 Jul 2028 (estimated)
  4. Study completion20 Jul 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
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04655755
Sponsor's protocol ID
2020-0129
Other IDs
NCI-2020-09915, 2020-0129
Status last verified
Sep 2026
First submitted
30 Nov 2020
Last updated
4 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bataller A, Montalban-Bravo G, Bazinet A, Alvarado Y, Chien K, Venugopal S, Ishizawa J, Hammond D, Swaminathan M, Sasaki K, Issa GC, Short NJ, Masarova L, Daver NG, Kadia TM, Colla S, Qiao W, Huang X, Kanagal-Shamanna R, Hendrickson S, Ravandi F, Jabbour E, Kantarjian H, Garcia-Manero G. Oral decitabine plus cedazuridine and venetoclax in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: a single-centre, phase 1/2 study. Lancet Haematol. 2024 Mar;11(3):e186-e195. doi: 10.1016/S2352-3026(23)00367-8. Epub 2024 Feb 2.

    PubMed 38316133

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Decitabine and Cedazuridine and Venetoclax in people with Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome, 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 8 inclusion and 17 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 4 Sep 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?

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?

Incidence and severity of all reported adverse events (Phase I) (time frame: Up to 28 days). 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 NCT04655755, 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 4 Sep 2026.

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