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

NCT05549661 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: MC210807NCI-2022-07695R01CA27249622-005600
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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). Onvansertib is a drug that binds to and inhibits an enzyme called PLK1, preventing cancer cell proliferation and causing cell death.

Conditions

Recurrent Chronic Myelomonocytic Leukemia; Refractory Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Not Otherwise Specified; Recurrent Atypical Chronic Myeloid Leukemia; Recurrent Myelodysplastic/Myeloproliferative Neoplasm; Refractory Myelodysplastic/Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (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.

  Up to 4 years

Secondary Outcomes (4)

• Complete response (CR) rate

  Up to 4 years

• Overall remission rate (ORR)

  Up to 4 years

• Volumetric spleen response

  Up to 4 years

• Constitutional symptoms

  Up to 4 years

Study Arms (1)

Treatment (onvansertib)

EXPERIMENTAL

Patients 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Onvansertib; Procedure: Ultrasound Imaging

Interventions

Onvansertib DRUG

Given PO

Also known as: 'PLK1 Inhibitor PCM-075, NMS-1286937, PCM 075, PCM-075, PLK-1 Inhibitor PCM-075, Polo-like Kinase 1 Inhibitor NMS-1286937, Polo-like Kinase 1 Inhibitor PCM-075

Treatment (onvansertib)

Ultrasound Imaging PROCEDURE

Undergo ultrasound imaging

Also known as: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography, Ultrasound, Ultrasound Test, Ultrasound, Medical, US

Treatment (onvansertib)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (onvansertib)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (onvansertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myelodysplastic-Myeloproliferative Diseases

Interventions

Specimen Handling; Biopsy; onvansertib; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Mrinal S. Patnaik, MBBS

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 22, 2022
• Study Start: April 4, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)