Refractory Chronic Myelomonocytic Leukemia Clinical Trial
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
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.
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. ;
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