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

ConditionsRecurrent Chronic Myelomonocytic LeukemiaRefractory Chronic Myelomonocytic LeukemiaMyelodysplastic/Myeloproliferative Neoplasm, Not Otherwise SpecifiedRecurrent Atypical Chronic Myeloid LeukemiaRecurrent Myelodysplastic/Myeloproliferative NeoplasmRefractory Myelodysplastic/Myeloproliferative Neoplasm
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Bone Marrow Aspiration and Biopsy

    Procedure/Surgery

    Undergo bone marrow aspiration and biopsy

  • Onvansertib

    Drug

    Given PO

  • Ultrasound Imaging

    Procedure/Surgery

    Undergo ultrasound imaging

Treatment groups

25 Participants
are divided into 1 treatment group
Group A: Treatment (onvansertib)Experimental treatment 4 interventions

Trial outcomes

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.

Time frame
Up to 4 years

Secondary outcomes

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).

Time frame
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.

Time frame
Up to 4 years
3

Volumetric spleen response

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

Time frame
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.

Time frame
Up to 4 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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