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Recurrent Chronic Myelomonocytic LeukemiaPhase 1NCT05549661

Onvansertib for the Treatment of Recurrent or Refractory Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome/MPN Overlap Neoplasms

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Onvansertib in people with Recurrent Chronic Myelomonocytic Leukemia and Refractory Chronic Myelomonocytic Leukemia, run by Mayo Clinic 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 I trial evaluates the safety, effectiveness, and best dose of onvansertib for the treatment of patients with chronic myelomonocytic leukemia and Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap neoplasms that has come back (recurrent) or that does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Onvansertib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
4 Apr 2023to 1 Dec 2027
Phase
Phase 1
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

  • PRE-REGISTRATION - INCLUSION CRITERIA:
  • Age >= 18 years
  • History of World Health Organization (WHO)-defined diagnosis of proliferative CMML (WBC count >= 13,000/mm^3 at time of diagnosis), or MDS/MPN overlap neoplasm with WBC count >= 13,000/mm3 at time of diagnosis (atypical CML and MDS/MPN-NOS).
  • NOTE: Hydroxyurea or hypomethylating induced leukopenia does not preclude inclusion. Discussion of WBC < 13,000/mm^3 due to treatment at the time of preregistration must be discussed with the Sponsor/Principal Investigator
  • Relapsed/refractory following treatment with hydroxyurea; or at least 4 cycles of treatment with hypomethylating agents; or who are intolerant of treatment with either therapy. Note: Prior exposure to erythropoiesis stimulating agents is allowed. Hydroxyurea may continue for the first 28 days on study. Continuation of hydroxyurea beyond the first cycle must be discussed with the Sponsor/Principal Investigator
  • Willing and able to review, understand, and provide written consent before starting any study-specific procedures or therapy
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  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willingness to provide mandatory bone marrow specimens for correlative research
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Recovered to grade 1 or baseline or established as sequelae from all toxic effects of previous therapy except alopecia
  • Platelet count >= 20,000/mm^3 (obtained =< 14 days prior to pre-registration)
  • NOTE: For platelet count < 20,000/mm3 and in situations where the primary investigator deems the thrombocytopenia to be attributable to the underlying CMML, patients can be enrolled as long as they are able to achieve a platelet count of 20,000/mm3 with transfusional support
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (=< 3 x ULN for patients with Gilbert's syndrome) (obtained =< 14 days prior to pre-registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 days prior to pre-registration)
  • Estimated glomerular filtration rate (eGFR) >= 50 mL/min/m^2 using one of the following methods (obtained =< 14 days prior to pre-registration):
  • Chronic Kidney Disease-Epidemiology Collaboration (CKDEPI) 2021 formula
  • Corrected creatinine clearance via serum and 24-hour urine creatinine assessment
  • Iothalamate/Iohexol glomerular filtrate rate via plasma/urine assessment
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Willingness to provide mandatory blood specimens for correlative research
  • REGISTRATION - INCLUSION CRITERIA:
  • Histological confirmation of WHO-defined diagnosis of a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) including one of the following (NOTE: to confirm patient is still eligible and has not progressed to
  • AML):
  • Proliferative CMML
  • Atypical chronic myeoloid leukemia (aCML)
  • MDS/MPN not otherwise specified (MDS/MPN, NOS)
  • NOTE: Hydroxyurea or hypomethylating agent induced leukopenia does not preclude inclusion. Discussion of WBC < 13,000/mm^3 due to treatment at the time of registration must be discussed with the Sponsor/Principal Investigator.
  • For a man or a woman of child-bearing potential (WOCBP): Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days after the final dose of any study drug. Adequate contraception is defined as follows:
  • Complete true abstinence
  • Consistent and correct use of one of the following methods of birth control:
  • Male partner who is sterile prior to the female patient's entry into the study and is the sole sexual partner for that female patient
  • Implants of levonorgestrel
  • Injectable progestogen
  • Intrauterine device (IUD) with a documented failure rate of less than 1% per year
  • Oral contraceptive pill (either combined or progesterone only)
  • Barrier method, for example: diaphragm with spermicide or condom with spermicide in combination with either implants of levonorgestrel or injectable progestogen
  • WOCBP must have a negative serum or urine pregnancy test =< 7 days prior to registration
  • NOTE: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea > 12 consecutive months); or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an IUD or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (eg, vasectomy), must be considered to be of child-bearing potential
  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Who cannot join

  • PRE-REGISTRATION - EXCLUSION CRITERIA:
  • Previous exposure to an alternative (investigational) PLK1 inhibitor
  • Demonstration of transformation to acute leukemia on any prior bone marrow biopsy
  • Prior allogeneic hematopoietic stem cell transplantation with active grade 2-4 graft-versus-host disease (GVHD) or with moderate to severe chronic GVHD
  • NOTE: The patient should not have received calcineurin inhibitors ≤28 days prior to pre-registration and should not be actively receiving immunosuppressive therapy for acute or chronic GVHD.
  • NOTE: CMML or MDS/MPN overlap neoplasms relapse after allogeneic stem cell transplant is allowed as long as they are >100 days after transplant and do not have the aforementioned GVHD criteria.
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  • Active central nervous system disease
  • Concurrent active malignancy, except adequately treated nonmelanoma skin cancer. History of curatively treated in situ cancer of the cervix, curatively treated in situ cancer of the breast, or other solid tumors curatively treated is allowed as long as there is no evidence of disease for > 2 years
  • NOTE: Precursor states such as monoclonal gammopathy of undetermined significance (MGUS), monoclonal B-cell lymphocytosis (MBL), and indolent lymphoproliferative disorders must be discussed with the Sponsor/Principal Investigator.
  • New York Heart Association (NYHA) class III/IV heart failure or active angina/angina equivalents
  • Anticancer chemotherapy (exception: hydroxyurea) or biologic therapy administered within 2 weeks (and at least 4 elimination half-lives for clinical trial agents) prior to pre-registration. NOTE: Hydroxyurea is allowed for the first 28 days on study. Continuation of hydroxyurea beyond the first cycle must be discussed with the Sponsor/Principal Investigator
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Major surgery =< 6 weeks prior to pre-registration
  • Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would significantly impede the absorption of an oral agent (eg, intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection)
  • Unable or unwilling to swallow study drug
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant nonhealing or healing wounds, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known active infection with human immunodeficiency virus (HIV) with measurable viral titer, hepatitis B surface antigen positivity, or hepatitis C with measurable viral titer. NOTE: Patients with antibody to hepatitis B core antibody are eligible if they have no measurable viral titer. Patients who have had a hepatitis B virus (HBV) immunization are eligible
  • Patient is receiving any live vaccine (eg, varicella, pneumococcus) =< 28 days prior to pre-registration. NOTE: messenger ribonucleic acid (mRNA)-based (eg, Pfizer or Moderna) or replication-deficient virus (eg, Oxford/AstraZeneca) COVID19 vaccines are permitted
  • Disease requiring systemic treatment with systemic immunosuppression with steroid steroids at a dose of >= 20 mg/day prednisone (or equivalent). Exceptions: Intermittent use of bronchodilators or inhaled steroids, local steroid injections, topical steroids
  • Any active disease condition that would render the protocol treatment dangerous or impair the ability of the patient to receive study drug
  • Strong CYP3A4 inhibitors/inducers as identified per institutional guidelines
  • QT interval with Fridericia's correction (QTcF) > 470 milliseconds. In the case of potentially correctible causes of QT prolongation, (eg, medications, hypokalemia), the electrocardiogram (ECG) may be repeated once during screening and that result may be used to determine eligibility
  • REGISTRATION - EXCLUSION CRITERIA:
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Increased risk of Torsade des Pointes (TdP) defined as follows:
  • A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval > 480 msec [CTCAE Grade >= 2] using Fredericia's QT correction formula)
  • A history of additional risk factors for TdP (eg. heart failure, family history of long QT syndrome)
  • Transformation to acute leukemia on registration bone marrow biopsy

Trial locations and contacts

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

Clinical Trials Referral Office contact

855-776-0015

mayocliniccancerstudies@mayo.edu

United States1 site, 1 recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Clinical Trial Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Mrinal S. Patnaik, MBBS

    Recruiting

Other trials in United States

About this study

Official title: Phase 1 Study to Determine the Safety and Efficacy of Onvansertib, A Novel, Oral, PLK1 Inhibitor in Patients With Proliferative Chronic Myelomonocytic Leukemia (CMML) and Myelodysplastic Syndrome/MPN Overlap Neoplasms Relapsed/Refractory or Intolerant to Available Therapies

This phase I trial evaluates the safety, effectiveness, and best dose of onvansertib for the treatment of patients with chronic myelomonocytic leukemia and Myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap neoplasms that has come back (recurrent) or that does not respond to treatment (refractory). Onvansertib is a drug that binds to and inhibits an enzyme called PLK1, preventing cancer cell proliferation and causing cell death.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Characterization of adverse events (AEs) by type, incidence, severity [graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0], seriousness, and relationship to treatment; effects on vital signs and laboratory parameters; changes from baseline in electrocardiograms (ECGs), physical examinations, weight, and Eastern Cooperative Oncology Group (ECOG) performance status.

SECONDARY OBJECTIVES:

  1. Efficacy: complete response (CR) rate, according to the 2015 myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) International Working Group (IWG) criteria.

II. Overall remission rate (ORR), defined as CR + complete cytogenetic remission + partial remission (CR+ complete cytogenetic remission [CCR] + partial remission [PR]).

III. Volumetric spleen response rate, as determined by ultrasound scan (US). IV. Constitutional symptoms, as assessed by the MPN-Symptom Assessment Form (SAF) total symptom score (TSS).

EXPLORATORY OBJECTIVES:

  1. Onvansertib activity in RAS mutant subtypes of proliferative chronic myelomonocytic leukemia (CMML).

II. Monocyte subset analysis by flow cytometry (CD14/CD16). III. Relation of genomic backgrounds and changes, as assessed by next generation sequencing (NGS), to response.

IV. Relation between changes in mutant circulating-tumor deoxyribonucleic acid (ctDNA) and response.

  1. CR rate, ORR and spleen response rate as per the 2015 MDS/MPN IWG response criteria.

VI. Assessment of target engagement. VII. Expression levels of PLK1 and KMT2A.

OUTLINE: This is a dose-escalation study of onvansertib followed by a dose-expansion study.

Patients receive onvansertib orally (PO) once daily (QD) on study. Patients also undergo bone marrow aspiration and biopsy, collection of blood samples, and ultrasound imaging during screening and throughout the trial.

Being tested
Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Onvansertib, Ultrasound Imaging
Medical subject headings
Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Myelodysplastic-Myeloproliferative Diseases

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, Specimen Collection

    Undergo collection of blood samples

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • OnvansertibDrug

    Also called 'PLK1 Inhibitor PCM-075, NMS-1286937, PCM 075, PCM-075

    Given PO

  • Ultrasound ImagingProcedure or surgery

    Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography

    Undergo ultrasound imaging

Study groups in NCT05549661
Study groupRoleWhat they receive
Treatment (onvansertib)ExperimentalPatients receive onvansertib PO QD on study. Patients also undergo bone marrow aspiration and biopsy, collection of blood samples, and ultrasound imaging during screening and throughout the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Onvansertib; Procedure: Ultrasound Imaging

What is being measured

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

  1. Incidence of adverse events

    Safety will be assessed primarily based on reported adverse events (AEs). The severity of AEs will be graded as mild, moderate, severe, or life-threatening according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All reported toxicities, regardless of attribution, will be summarized by toxicity type and maximum grade, and sorted by number of patients experiencing the toxicity. The maximum grade consolidates the reports of a given toxicity for a patient over time by taking the maximum across time.

    Measured: Up to 4 years

Secondary outcomes (4)

  1. Complete response (CR) rate

    CR will be determined by the International Working Group (IWG) response criteria. CR rate will be presented descriptively for each cohort, with 95% confidence intervals (CIs).

    Measured: Up to 4 years

  2. Overall remission rate (ORR)

    ORR is defined as CR + complete cytogenetic remission + partial response and will be determined by the IWG response criteria. ORR will be presented descriptively for each cohort, with 95% CIs.

    Measured: Up to 4 years

  3. Volumetric spleen response

    Spleen volumes, as determined by ultrasound, will be summarized descriptively for each cohort.

    Measured: Up to 4 years

  4. Constitutional symptoms

    The Myeloproliferative Neoplasm-Symptom Assessment Form total symptom score will be summarized descriptively for each cohort. Symptom scores will also be summarized individually.

    Measured: Up to 4 years

Timeline

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

  1. First posted22 Sep 2022
  2. Study start4 Apr 2023
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Dec 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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05549661
Sponsor's protocol ID
MC210807
Other IDs
NCI-2022-07695, R01CA272496, 22-005600
Status last verified
Jun 2026
First submitted
19 Sep 2022
Last updated
22 Jun 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 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Biopsy and Onvansertib in people with Recurrent Chronic Myelomonocytic Leukemia and Refractory Chronic Myelomonocytic Leukemia, run by Mayo Clinic 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 39 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: looking for participants now, as of the sponsor's last update on 22 Jun 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 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.

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 Clinical Trials Referral Office (855-776-0015, mayocliniccancerstudies@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 4 years). 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 NCT05549661.

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 22 Jun 2026.

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