Onvansertib for Chronic Myelomonocytic Leukemia

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: Active CNS disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called onvansertib to determine its safety and effectiveness in treating chronic myelomonocytic leukemia (CMML) and related blood disorders that have recurred or resist treatment. Onvansertib blocks an enzyme that aids cancer cell growth, leading to cell death. The trial seeks participants with CMML or similar conditions whose disease has returned or resists standard treatments. Participants should attend follow-up visits and be willing to provide bone marrow and blood samples for research. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial allows the continuation of hydroxyurea for the first 28 days, but other anticancer chemotherapy or biologic therapy must be stopped at least 2 weeks before joining the trial. If you are taking hydroxyurea beyond the first cycle, it must be discussed with the study's Sponsor/Principal Investigator.

Is there any evidence suggesting that onvansertib is likely to be safe for humans?

Research has shown that onvansertib is being tested for safety in treating certain blood cancers, such as chronic myelomonocytic leukemia and related conditions. Onvansertib blocks an enzyme called PLK1, which aids cancer cell growth.

Since onvansertib remains in early testing stages, detailed safety information is limited. However, early trials provide insights into patient tolerance and potential side effects. This phase 1 trial primarily focuses on determining the safest dose and identifying any potential issues.

Onvansertib has not yet received approval for these specific conditions, so monitoring trial updates is crucial for understanding its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Onvansertib is unique because it targets a specific enzyme called PLK1, which plays a crucial role in cancer cell division. Most treatments for chronic myelomonocytic leukemia (CMML), such as hypomethylating agents like azacitidine and decitabine, focus on modifying the gene expression in cancer cells. Onvansertib, on the other hand, disrupts the cell cycle directly, which might lead to more effective cancer cell death. Researchers are excited about this approach because it offers a novel mechanism of action that could potentially improve outcomes for patients with CMML.

What evidence suggests that onvansertib might be an effective treatment for chronic myelomonocytic leukemia?

Research shows that onvansertib, the investigational treatment in this trial, targets a protein called PLK1, which aids cancer cell growth. By blocking PLK1, onvansertib aims to stop cancer cells from multiplying and induce their death. Early studies have shown that onvansertib can effectively treat cancers with a specific change in the RAS pathway, common in some blood cancers like chronic myelomonocytic leukemia. These promising early results suggest that the drug could benefit patients whose cancer has returned or isn't responding to other treatments. While there is hope based on its mechanism, more information is needed to fully understand its effectiveness. ^{1 2 3 5 6}

Who Is on the Research Team?

Mrinal Patnaik, MBBS

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with chronic myelomonocytic leukemia that's returned or isn't responding to treatment, who've had specific prior treatments and have a certain level of health (good organ function, no severe concurrent illnesses). They must be able to consent, complete questionnaires, provide samples for research, and agree to use effective contraception.

Inclusion Criteria

Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 days prior to pre-registration)

Platelet count >= 20,000/mm^3 (obtained =< 14 days prior to pre-registration)

Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria

I have a type of blood disorder that is not CMML.

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant persons, Nursing persons, Persons of childbearing potential who are unwilling to employ adequate contraception, Increased risk of Torsade des Pointes (TdP) defined as follows: A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval > 480 msec [CTCAE Grade >= 2] using Fredericia's QT correction formula), A history of additional risk factors for TdP (eg. heart failure, family history of long QT syndrome)

I have been treated with a PLK1 inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose-escalation

Patients receive onvansertib orally once daily to determine the maximum tolerated dose

8-12 weeks

Weekly visits (in-person) for dose adjustments and monitoring

Dose-expansion

Patients continue receiving onvansertib at the determined dose to evaluate efficacy and safety

Up to 4 years

Monthly visits (in-person) for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Onvansertib

Trial Overview The trial is testing Onvansertib's safety and optimal dose. It involves collecting biological specimens and performing bone marrow biopsies plus ultrasound imaging. Onvansertib targets an enzyme in cancer cells to stop their growth and cause cell death.

How Is the Trial Designed?

Group I: Treatment (onvansertib) Experimental Treatment 4 Interventions

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.

Onvansertib is already approved in United States, European Union for the following indications:

Approved in United States as Onvansertib for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

Approved in European Union as Onvansertib for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Olverembatinib is a novel oral tyrosine kinase inhibitor that effectively targets the T315I mutation in the BCR::ABL1 tyrosine kinase, which is a significant cause of resistance in chronic myeloid leukemia (CML) treatment.

Recent studies suggest that olverembatinib is a safe and effective treatment option for CML patients with the T315I mutation, addressing a critical challenge in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib in chronic myeloid leukemia. Öziskender, R., Eşkazan, AE.[2022]

Avapritinib, a selective inhibitor for the KIT D816V mutation, showed a high overall response rate of 71% in patients with advanced systemic mastocytosis (AdvSM) who had previously received systemic therapy, with a median time to response of 2.3 months.

The treatment was generally well tolerated, with 94% of patients experiencing treatment-related adverse events, mostly mild (grade 1/2), and 81% remaining on treatment after 6 months, indicating its safety profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Reiter, A., Schwaab, J., DeAngelo, DJ., et al.[2022]

Dasatinib treatment for chronic phase CML patients who are resistant to standard-dose imatinib results in an average gain of 0.67 life-years and 0.62 quality-adjusted life-years (QALYs) compared to high-dose imatinib.

The cost-effectiveness analysis shows that dasatinib costs EUR 6880 per QALY gained, indicating it is a financially viable treatment option for imatinib-resistant CML patients in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of dasatinib versus high-dose imatinib in patients with Chronic Myeloid Leukemia (CML), resistant to standard dose imatinib--a Swedish model application. Ghatnekar, O., Hjalte, F., Taylor, M.[2015]

Chronic myeloid leukemia (CML) has seen significant advancements in treatment, particularly with the development of imatinib mesylate, which targets the Bcr-Abl gene fusion and has led to durable remission in many patients.

Despite the effectiveness of imatinib, about one-third of CML patients may require alternative therapies due to issues like drug intolerance or resistance, highlighting the need for ongoing research into new treatment options and understanding resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing resistance in chronic myeloid leukemia. Roychowdhury, S., Talpaz, M.[2017]

Dasatinib, a novel oral multi-targeted kinase inhibitor, effectively inhibits BCR-ABL and SRC family kinases in chronic myeloid leukemia (CML), showing promising results in preclinical models and in patients resistant or intolerant to imatinib.

The study found that dasatinib significantly reduces levels of phospho-BCR-ABL and phospho-CrkL in tumor models, with effective plasma concentrations predicted to be achievable in CML patients, indicating its potential as a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib (BMS-354825) pharmacokinetics and pharmacodynamic biomarkers in animal models predict optimal clinical exposure. Luo, FR., Yang, Z., Camuso, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05549661

NCT05549661 | Onvansertib for the Treatment of Recurrent ... This phase I trial evaluates the safety, effectiveness, and best dose of onvansertib for the treatment of patients with chronic myelomonocytic leukemia and ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20540775

Onvansertib for the Treatment of Recurrent or Refractory ... This phase I trial evaluates the safety, effectiveness, and best dose of onvansertib for the treatment of patients with chronic myelomonocytic leukemia that ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05549661?term=PLK1&viewType=Table&rank=3

Study Details | Onvansertib for the Treatment of Recurrent ... A general description of the clinical trial arm. It identifies the role of the intervention that participants receive. Types of arms include experimental arm, ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT399134

Phase 1 study to determine the safety and efficacy of ... MP-CMML is enriched in RAS pathway mutations (NRAS, CBL, KRAS, PTPN11 and NF1), has a shorter median survival (19 vs 36 months), has a higher rate of acute ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05549661/onvansertib-for-the-treatment-of-recurrent-or-refractory-chronic-myelomonocytic-leukemia

Onvansertib for the Treatment of Recurrent or Refractory ... This phase I trial evaluates the safety, effectiveness, and best dose of onvansertib for the treatment of patients with chronic ...

6. go.drugbank.com go.drugbank.com/drugs/DB15110

Onvansertib: Uses, Interactions, Mechanism of Action Onvansertib is under investigation in clinical trial NCT03303339 (Onvansertib in Combination With Either Low-dose Cytarabine or Decitabine ...