Ignite Creation Date:
2025-12-24 @ 12:19 PM
Ignite Modification Date:
2025-12-29 @ 3:51 AM
Study NCT ID:
NCT05549661
Status:
RECRUITING
Last Update Posted:
2025-02-14
First Post:
2022-09-19
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Onvansertib for the Treatment of Recurrent or Refractory Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome/MPN Overlap Neoplasms
Sponsor:
Mayo Clinic
Organization:
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
Detailed Description:
PRIMARY OBJECTIVE:
I. 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:
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.
I. 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:
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2022-07695 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| R01CA272496 | NIH | None | https://reporter.nih.gov/quic… | View |
| 22-005600 | OTHER | Mayo Clinic Institutional Review Board | View |