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Secondary Myelodysplastic SyndromePhase 2NCT05379166

Venetoclax and Azacitidine for Treatment of Therapy Related or Secondary Myelodysplastic Syndrome

A Phase 2 study testing Azacitidine, Quality-of-Life Assessment and Questionnaire Administration in people with Secondary Myelodysplastic Syndrome and Therapy-Related Myelodysplastic Syndrome, run by Uma Borate at 3 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 II trial studies the effect of venetoclax and azacitidine in treating patients with therapy related or secondary myelodysplastic syndrome. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine, Quality-of-Life Assessment and Questionnaire Administration
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
3 sitesUnited States
Study dates
23 Jun 2022to 15 Dec 2026
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

  • Ability to understand and the willingness to sign a written informed consent document
  • Age >= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Previously untreated therapy related myelodysplastic syndrome (t-MDS) with Revised International Prognostic Scoring System (IPSS-R) risk categories Intermediate, High or Very High (i.e., minimum IPSS-R score of 3.5) and presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate
  • Patients with t-MDS which is defined as patients who have had prior anti-cancer therapy including chemotherapy and/or radiation therapy
  • Aspartate aminotransferase (AST) < 3.0 x upper limit of normal (ULN) x upper limit of normal (ULN; local laboratory)
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  • Alanine aminotransferase (ALT) < 3.0 x ULN x ULN
  • Total bilirubin =< 2 x ULN (except for patients with known Gilbert's syndrome)
  • Creatinine clearance >= 30 mL/min OR serum creatinine < 1.5 x the ULN
  • White blood cell (WBC) count =< 10,000/uL
  • Note: Treatment with hydroxyurea is permitted to lower the WBC to reach this inclusion criterion. The WBC should be determined >= 24 hours after the last dose of hydroxyurea. The last dose of hydroxyurea should not be administered =< 3 days prior to the first dose of azacitidine
  • Females of childbearing potential (FOCBP) must agree to adequate contraception (1 form of contraception or abstinence) from the screening visit until 30 days following the last dose of venetoclax. 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
  • FOCBP are those who have not been surgically sterilized or have not been free from menses for > 1 year without an alternative medical cause
  • Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 90 days after the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment

Who cannot join

  • Participant has received prior therapy with a venetoclax or other BH3 mimetic. Note: Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy. Supportive care should be discontinued >= 14 days prior to the first dose of study drug. Subjects may continue oral corticosteroids for management of conditions other than MDS (e.g., asthma, rheumatoid arthritis) at a stable daily dose equivalent to =< 10 mg prednisone during screening and study participation
  • Subject has a diagnosis other than previously untreated de novo MDS with IPSS-R risk categories Intermediate, High or Very High, including:
  • MDS with IPSS-R risk categories Very Low or Low (overall IPSS score < 3)
  • MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
  • MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
  • Patients who are suitable for and willing to receive intensive chemotherapy or eligible to proceed to allogeneic stem cell transplantation without additional therapy
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  • Known history of testing positive for Human Immunodeficiency Virus (HIV) infections, Hepatitis B, or Hepatitis C. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
  • Clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
  • Patients with uncontrolled infection will not be enrolled until infection is treated and under control
  • Hypersensitivity to any study agent when administered alone. Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
  • Any psychiatric illness that prevents patient from informed consent process
  • Pregnant of breastfeeding at the time of enrollment
  • Subject has received allogeneic HSCT or solid organ transplantation
  • Subject has a concurrent active malignancy requiring treatment or with an expected life expectancy less than 1 year with the exception of below. Any subject with a concurrent active malignancy will be reviewed by the PI for eligibility prior to enrollment
  • Adequately treated in situ carcinoma of the cervix uteri
  • Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
  • Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy
  • Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
  • Ongoing systemic infection (viral, bacterial, or fungal)
  • Acute pneumonia
  • Febrile neutropenia
  • Subject has received strong or moderate CYP3A inducers within 7 days prior to the first dose of study drug
  • Subject has received strong or moderate CYP3A inhibitors within 7 days prior to the first dose of study drug
  • Subject has consumed one or more of the following within 3 days prior to the first dose of study drug:
  • Grapefruit or grapefruit products
  • Seville oranges (including marmalade containing Seville oranges)
  • Star fruit (carambola)
  • Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration
  • Subject has history of a cardiovascular, endocrinologic, hepatic, immunologic metabolic, neurologic, psychiatric, pulmonary, renal disease, or any other condition that in the opinion of the investigator would adversely affect his/her participation in this study or interpretation of study results
  • Subject has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Oregon Health & Science University

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: Phase II Study of Clinical Efficacy of Venetoclax in Combination With Azacitidine in Patients With Therapy Related Myelodysplastic Syndrome (t-MDS)

This phase II trial studies the effect of venetoclax and azacitidine in treating patients with therapy related or secondary myelodysplastic syndrome. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, 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. Giving venetoclax in combination with azacitidine may work better in treating patients with therapy related or secondary myelodysplastic syndrome.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the proportion of participants that achieve a complete remission following treatment with azacitidine and venetoclax.

SECONDARY OBJECTIVES:

  1. Assess safety of azacitidine and venetoclax combination therapy. II. Determine the overall response rate (ORR). III. Determine the complete cytogenetic response rate (CCyR). IV. Determine the duration of response (DOR). V. Estimate event-free survival (EFS). VI. Estimate overall survival (OS). VII. Determine combined hematologic improvement rate (HIR). VIII. Determine red blood cell transfusion independence rate. IX. Determine platelet transfusion independence rate. X. Determine proportion of participants whose disease transforms to acute myeloid leukemia (AML).

XI. Determine proportion of participants that proceed to allogeneic hematopoietic stem cell transplantation (alloHSCT).

XII. Compare response criteria between the 2006 International Working Group (IWG) and 2023 IWG criteria.

EXPLORATORY OBJECTIVES:

  1. Determine baseline frequencies of cytogenetic aberrations and their relationships to response to study therapy.

II. Estimate progression-free survival (PFS). III. Obtain quality of life (QoL) information from patient-reported responses to Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a and European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) - Core 30 (C30) questionnaires.

OUTLINE:

Patients receive venetoclax orally (PO) once daily (QD) on days 1-14 and azacitidine intravenously (IV) over 10-40 minutes on days 1-7 or days 1-5 of week 1 and days 1 and 2 of week 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 6 months for up to 24 months.

Being tested
Azacitidine, Quality-of-Life Assessment, Questionnaire Administration, Venetoclax

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • VenetoclaxDrug

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

    Given PO

Study groups in NCT05379166
Study groupRoleWhat they receive
Treatment (venetoclax, azacitidine)ExperimentalPatients receive venetoclax PO QD on days 1-14 and azacitidine IV over 10-40 minutes on days 1-7 or days 1-5 of week 1 and days 1 and 2 of week 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Azacitidine; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Venetoclax

What is being measured

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

  1. Complete remission (CR)

    Defined by 2023 International Working Group (IWG) criteria. A point estimate and 95% exact (i.e., Clopper-Pearson) confidence interval will be computed for the CR rate within the efficacy-evaluable population.

    Measured: At the end of Cycle 4 (each cycle is 28 days) or earlier based on bone marrow results

Secondary outcomes (13)

  1. Treatment emergent adverse events (AEs)

    AEs defined by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. Participant-level tallies of treatment emergent adverse events will be reported overall and by System Organ Class (according to Medical Dictionary for Regulatory Activities [MedDRA]), with separate tables of frequency counts and percentages made for grade >= 3 AEs and serious AEs. Moreover, AE attributions will be utilized so that specific categories of study drug-related adverse reactions (e.g., at least possibly related; definitely related) can also be tallied and summarized by Organ Class.

    Measured: Up to 30 days after last dose of study drug

  2. Overall response rate (ORR)

    The ORR rate (proportion of participants achieving a CR, CR equivalent, partial remission [PR], CR with limited count recovery (CRL), CR with partial hematologic recovery (CRh), or Hematologic Improvement (HI)) will be described with a point estimate and 95% exact confidence interval for the efficacy-evaluable population.

    Measured: At the end of the last cycle of study drug (each cycle is 28 days)

  3. Cytogenetic response rate (CCyR)

    The CCyR rate, applied to the set of participants whose bone marrow shows an abnormal karyotype at baseline and who are subjected to at least one post- study drug chromosomal G banding analysis, will be estimated along with a 95% exact confidence interval.

    Measured: At the end of the last cycle of study drug (each cycle is 28 days)

  4. Overall survival (OS)

    OS distributions will be estimated with the Kaplan Meier method, with estimates for median survival and survival rates at landmark times (e.g., 1-year) provided.

    Measured: From date of death or the last known alive date for participants who withdraw from or complete the study without dying, assessed up to 24 months

  5. Duration of response (DOR)

    Measured: From earliest occurrence of PR, mCR, or CR to onset of progressive disease, assessed up to 24 months

  6. Event free survival (EFS)

    EFS distributions will be estimated with the Kaplan Meier method, with estimates for median survival and survival rates at landmark times (e.g., 1-year) provided.

    Measured: From event date or date of last clinic visit for participants without an event during the study period, assessed up to 24 months

  7. Hematologic improvement rate (HIR)

    Within the hematologic improvement analysis set, the number and percentage (with exact 95% confidence interval) of participants with HIR will be listed.

    Measured: At the end of the last cycle of study drug (each cycle is 28 days)

  8. Rates of hematologic improvement-erythrocytes (HI-E)

    Rates of HI-E will be computed along with exact 95% confidence intervals and associated sample sizes.

    Measured: At the end of the last cycle of study drug (each cycle is 28 days)

  9. Rates of hematologic improvement-platelets (HI-P)

    Rates of HI-P will be computed along with exact 95% confidence intervals and associated sample sizes.

    Measured: At the end of the last cycle of study drug (each cycle is 28 days)

  10. Rates of hematologic improvement-neutrophils (HI-N)

    Rates of HI-N will be computed along with exact 95% confidence intervals and associated sample sizes.

    Measured: At the end of the last cycle of study drug (each cycle is 28 days)

  11. Percentage of participants who have disease that transforms to acute myeloid leukemia (AML)

    Will be estimated with exact 95% confidence intervals for the intent to treat (ITT) population, safety, and efficacy populations.

    Measured: End of study follow-up period (24 months after last dose of study drug)

  12. Percentage of participants who proceed to allogeneic hematopoietic stem cell transplantation

    Will be estimated with exact 95% confidence intervals for the ITT population, safety, and efficacy populations.

    Measured: 12 months after last dose of study drug

  13. Percentage of patients achieving CR, CR equivalent, CRi, CRh, PR, or HI

    Measured: From first dose of study drug to end of last cycle of study drug (each cycle is 28 days)

Timeline

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

  1. First posted18 May 2022
  2. Study start23 Jun 2022
  3. Primary completion27 Jan 2026
  4. Study completion15 Dec 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05379166
Sponsor's protocol ID
OSU-20420
Other IDs
NCI-2021-08484
Status last verified
May 2026
First submitted
15 Mar 2022
Last updated
14 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine, Quality-of-Life Assessment and Questionnaire Administration in people with Secondary Myelodysplastic Syndrome and Therapy-Related Myelodysplastic Syndrome, run by Uma Borate at 3 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 14 inclusion and 31 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 14 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 3 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 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 remission (CR) (time frame: At the end of Cycle 4 (each cycle is 28 days) or earlier based on bone marrow results). 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 NCT05379166.

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 14 May 2026.

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