Mayo Clinic
This phase I trial evaluates the safety, effectiveness, and best dose of onvansertib for the treatment of patients with chronic myelomonocytic leukemia 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.
Recurrent Chronic Myelomonocytic Leukemia
Refractory Chronic Myelomonocytic Leukemia
Biospecimen Collection
Bone Marrow Aspiration and Biopsy
Onvansertib
Ultrasound Imaging
Phase 1
PRIMARY OBJECTIVE: I. Characterization of adverse events (AEs) by type, incidence, severity (graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-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: I. 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: I. 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. V. 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.}}
Study Type : | Interventional |
Estimated Enrollment : | 25 participants |
Masking : | None (Open Label) |
Primary Purpose : | Treatment |
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) Relapsed/Refractory or Intolerant to Available Therapies |
Actual Study Start Date : | April 4, 2023 |
Estimated Primary Completion Date : | December 29, 2026 |
Estimated Study Completion Date : | March 8, 2027 |
Arm | Intervention/treatment |
---|---|
Experimental: Treatment (onvansertib) 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 |
Ages Eligible for Study: | 18 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.
Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905