What is the mechanism of action of this treatment?

Onvansertib, a PLK1 inhibitor, works by blocking the enzyme PLK1, essential for cancer cell division and survival, leading to cell cycle arrest and apoptosis. This targeted approach is significant for CMML patients as it may reduce malignant cell proliferation with fewer side effects. Other treatments, like hypomethylating agents (azacitidine and decitabine), reactivate tumor suppressor genes and induce cancer cell death. These mechanisms are vital for managing CMML, offering diverse strategies to control the disease and potentially improve patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for Chronic Myelomonocytic Leukemia (CMML) include hypomethylating agents like azacitidine and decitabine, as well as targeted therapies. For treatments similar to Onvansertib, which is a PLK1 inhibitor, side effects can include hematologic toxicities such as neutropenia, anemia, and thrombocytopenia. Non-hematologic side effects may include fatigue, gastrointestinal disturbances (nausea, vomiting, diarrhea), and potential liver enzyme abnormalities. It is important to monitor patients closely for these side effects to manage them effectively.

What prior FDA approvals exist?

There is no specific mention of FDA-approved PLK1 inhibitors for the treatment of Chronic Myelomonocytic Leukemia (CMML) in the provided context. Onvansertib, which is currently being studied for its efficacy in CMML, works by inhibiting the enzyme PLK1 to prevent cancer cell proliferation and induce cell death. Broadly, treatments for CMML often include hypomethylating agents like azacitidine and decitabine, which are commonly used for various myeloid malignancies.

What other types of research exist?

Promising novel alternatives to Onvansertib for CMML patients include: 1) Hypomethylating agents such as azacitidine and decitabine, which are standard treatments but continue to be refined and combined with other agents. 2) JAK2 inhibitors, particularly for patients with JAK2 mutations, as they target the JAK-STAT pathway involved in CMML. 3) Venetoclax, a BCL-2 inhibitor, which has shown promise in combination with hypomethylating agents in myeloid malignancies. 4) IDH1/2 inhibitors for patients with IDH1 or IDH2 mutations, targeting metabolic pathways in leukemia cells. These alternatives are based on their mechanisms of action and recent clinical trial data.

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PLK1 Inhibitor

Onvansertib for Chronic Myelomonocytic Leukemia

Phase 1

Recruiting

Led By Mrinal S. Patnaik, MBBS

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests onvansertib, a drug taken by mouth, for patients with chronic myelomonocytic leukemia that has returned or doesn't respond to other treatments. Onvansertib blocks an enzyme needed for cancer cells to grow, aiming to stop their growth and cause them to die.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While the side effects are not explicitly listed here, drugs like Onvansertib typically may cause fatigue, nausea, diarrhea, low blood counts leading to increased infection risk or bleeding problems. Organ-specific inflammation could also occur.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events

Secondary study objectives

Complete response (CR) rate

Constitutional symptoms

Overall remission rate (ORR)

+1 more

Side effects data

From 2021 Phase 1 & 2 trial • 72 Patients • NCT03303339

38%

Febrile neutropenia

31%

Hypokalaemia

28%

Diarrhoea

28%

Stomatitis

25%

Fatigue

22%

Nausea

22%

Epistaxis

19%

Oedema peripheral

19%

Platelet count decreased

19%

Alopecia

16%

Hypophosphataemia

16%

Acute myeloid leukaemia

16%

Sepsis

16%

Dyspnoea

16%

Cough

16%

Hypoalbuminaemia

13%

Hypoxia

13%

Lung infection

13%

Anaemia

13%

Rash maculo-papular

13%

Rash

13%

Hypocalcaemia

13%

Arthralgia

13%

Hypertension

13%

Hypotension

Electrocardiogram QT prolonged

Syncope

Pneumonia

Cellulitis

Headache

Abdominal pain upper

Oral pain

Staphylococcal infection

Urinary tract infection

Hypomagnesaemia

Dizziness

Oropharyngeal pain

Petechiae

Decreased appetite

Alanine aminotransferase increased

Abdominal pain

Escherichia bacteraemia

Blood creatine increased

Mucosal inflammation

Hyperbilirubinaemia

Pleural effusion

Vomiting

Dry skin

Fluid overload

Ear pain

Lower gastrointestinal haemorrhage

Dry mouth

Oral candidiasis

Neuropathy peripheral

Fall

Pyrexia

Nasal congestion

Ecchymosis

Blood alkaline phosphatase

Insomnia

Pain in extremity

Haematemesis

Odynophagia

Proctalgia

Staphylococcal bacteraemia

Bacteraemia

Pneumonia fungal

Pruritus

Dermatitis contact

Purpora

Non-cardiac chest pain

Hyperkalaemia

Hypercalcaemia

Flank pain

Aspartate aminotransferase increased

Neutrophil count decreased

Blood bilirubin increased

Pleuritic pain

Haematoma

Conjunctival haemorrhage

Myalgia

Back pain

Atrial fibrillation

Mallory-Weiss syndrome

Tumour lysis syndrome

Hyperglycaemia

Upper gastrointestinal haemorrhage

Pain

Respiratory failure

Rash pruritic

Musculoskeletal pain

Face oedema

Hyponatraemia

Contusion

Septic shock

Candida infection

Granulicatella bacteraemia

Kidney infection

Pancytopenia

Colitis

Melaena

Constipation

Transfusion reaction

Dysgeusia

Dyspnoea exertional

Wheezing

Neutropenia

Weight decreased

Anxiety

Eye pruritus

White blood cell count decreased

Neutropenic colitis

Mental status changes

Chills

Sinus tachycardia

Haemoptysis

Aphasia

100%

80%

60%

40%

20%

Study treatment Arm

Phase 2: Onvansertib 60 mg/m^2 + Decitabine

Phase 1b: Onvansertib 90 mg/m^2 + Decitabine

Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 12 mg/m^2 + Decitabine

Phase 1b: Onvansertib 40 mg/m^2 + Decitabine

Phase 1b: Onvansertib 60 mg/m^2 + Decitabine

Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 18 mg/m^2 + Decitabine

Phase 1b: Onvansertib 27 mg/m^2 + Decitabine

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (onvansertib)Experimental Treatment4 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ultrasound Imaging

2018

Completed Phase 4

~760

Bone Marrow Aspiration and Biopsy

2016

Completed Phase 1

~40

Biospecimen Collection

2004

Completed Phase 3

~2030

Onvansertib

2017

Completed Phase 2

~220

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Onvansertib, a PLK1 inhibitor, works by blocking the enzyme PLK1, essential for cancer cell division and survival, leading to cell cycle arrest and apoptosis. This targeted approach is significant for CMML patients as it may reduce malignant cell proliferation with fewer side effects. Other treatments, like hypomethylating agents (azacitidine and decitabine), reactivate tumor suppressor genes and induce cancer cell death. These mechanisms are vital for managing CMML, offering diverse strategies to control the disease and potentially improve patient outcomes.

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