What is the mechanism of action of this treatment?

The most common treatments for Chronic Myeloid Leukemia (CML) are Tyrosine Kinase Inhibitors (TKIs) like Bosutinib. These drugs target the BCR-ABL fusion protein, which is produced by the Philadelphia chromosome abnormality and has abnormal tyrosine kinase activity that drives the proliferation of leukemic cells. By inhibiting this kinase activity, TKIs reduce the growth of these malignant cells, leading to remission in many patients. This targeted approach is crucial for CML patients as it offers a more precise and effective treatment compared to traditional chemotherapies.

What side effects are associated with this type of intervention?

The most common treatments for Chronic Myeloid Leukemia (CML) using Tyrosine Kinase Inhibitors (TKIs) like Bosutinib often result in gastrointestinal issues such as diarrhea and skin reactions like rash. Severe side effects can include grade 3/4 diarrhea and rash. Other TKIs may also cause edema, dry eye, arthralgia, upper respiratory tract infections, hypertension, atrial fibrillation, and major hemorrhage. The severity and frequency of these side effects can vary among patients.

What prior FDA approvals exist?

The FDA has approved several Tyrosine Kinase Inhibitors (TKIs) for the treatment of Chronic Myeloid Leukemia (CML), which target the BCR-ABL kinase. Imatinib (Gleevec) was the first TKI approved and revolutionized CML treatment by specifically inhibiting the BCR-ABL fusion protein. Following Imatinib, second-generation TKIs such as Dasatinib (Sprycel) and Nilotinib (Tasigna) were approved, offering options for patients who are resistant or intolerant to Imatinib. More recently, Bosutinib (Bosulif) and Ponatinib (Iclusig) have been approved, providing further alternatives for patients with specific resistance mutations or those who have failed previous TKI therapies. These drugs have significantly improved the prognosis and management of CML by targeting the underlying molecular abnormality.

What other types of research exist?

Promising alternatives to Bosutinib for CML patients include: 1) Acalabrutinib, which has shown better tolerability and similar efficacy compared to Ibrutinib. 2) Zanubrutinib, which offers a balance of efficacy and tolerability. Both are Bruton tyrosine kinase (BTK) inhibitors and are approved in Europe, with ongoing regulatory evaluation in other regions.

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Tyrosine Kinase Inhibitor

Bosutinib for Chronic Myeloid Leukemia

Phase 1 & 2

Waitlist Available

Research Sponsored by Children's Oncology Group

Eligibility Criteria Checklist

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

Must have

Be younger than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, a maximum of around 10 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests bosutinib, a daily oral medication, in children with a type of leukemia. It aims to find a safe dose and see how well it works in those newly diagnosed or who haven't responded to other treatments. Bosutinib helps by blocking proteins that cancer cells need to grow. Bosutinib is a type of medication used for treating leukemia, especially in cases not responding to other treatments.

Who is the study for?

This trial is for pediatric patients aged 1-18 with newly diagnosed chronic phase Philadelphia chromosome-positive Chronic Myeloid Leukemia (Ph+ CML) or those resistant/intolerant to prior treatments. Participants must have proper bone marrow, kidney and liver function, not be pregnant, able to swallow medication whole, and willing to use effective contraception if applicable.

What is being tested?

The study tests the drug Bosutinib in children with Ph+ CML. It's an open-label trial meaning everyone knows what treatment they're getting. The goal is to find a safe dose for kids who are either newly diagnosed or haven't responded well to previous therapies and see how their bodies handle the drug.

What are the potential side effects?

While specific side effects for this pediatric trial aren't listed, Bosutinib can generally cause stomach issues like diarrhea, nausea; liver problems; rash; fatigue; muscle pain; and changes in blood test results which could indicate other potential side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, a maximum of around 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, a maximum of around 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, a maximum of around 10 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

1. Incidence (and severity) of Dose-Limiting Toxicities (DLTs) assessed during the first 28 days of treatment.

AEs, as characterized by type, frequency, severity (as graded using CTCAE version, v4.03), timing, seriousness, and relation to study therapy (pooled across ND and R/I CML patients and by line of therapy).

PK parameters of bosutinib: Apparent clearance (CL/F).

+6 more

Secondary study objectives

AEs, as characterized by type, frequency, severity (as graded using CTCAE version, v4.03), timing, seriousness, and relation to study therapy;

Duration of the respective responses by line of therapy

ECG abnormalities: PR interval

+9 more

Other study objectives

Parameters of bone metabolism and growth: bone age

Bone and Bones

Parameters of bone metabolism and growth: hormones associated with growth and pubertal development (IGF-1, T4, TSH and LH, FSH, estradiol for girls, and testosterone for boys)

+7 more

Side effects data

From 2020 Phase 3 trial • 536 Patients • NCT02130557

75%

Diarrhoea

37%

Nausea

36%

Thrombocytopenia

34%

Alanine aminotransferase increased

26%

Aspartate aminotransferase increased

23%

Abdominal pain

23%

Rash

22%

Anaemia

22%

Headache

21%

Vomiting

21%

Fatigue

21%

Lipase increased

18%

Arthralgia

16%

Pyrexia

13%

Constipation

13%

Asthenia

13%

Upper respiratory tract infection

13%

Nasopharyngitis

12%

Neutropenia

12%

Back pain

11%

Decreased appetite

11%

Cough

11%

Dyspnoea

11%

Pruritus

10%

Hypertension

10%

Abdominal pain upper

10%

Dyspepsia

10%

Urinary tract infection

10%

Pain in extremity

Influenza

Amylase increased

Dizziness

Leukopenia

Oedema peripheral

Bronchitis

Blood creatinine increased

Insomnia

Dry skin

Lymphopenia

Influenza like illness

Sinusitis

Blood alkaline phosphatase increased

Blood bilirubin increased

Anxiety

Oropharyngeal pain

Alopecia

Abdominal distension

Toothache

Blood creatine phosphokinase increased

Myalgia

Rash maculo-papular

Gastroenteritis

Muscle spasms

Pneumonia

Gastrooesophageal reflux disease

Face oedema

Weight increased

Hypophosphataemia

Bone pain

Depression

Vision blurred

Hypokalaemia

Night sweats

Cholecystitis acute

Myocardial ischaemia

Atrial fibrillation

Cardiac failure acute

Coronary artery disease

Pericarditis

Hepatitis

Hepatotoxicity

Cellulitis

Femoral neck fracture

Musculoskeletal chest pain

Rectal cancer

Unintended pregnancy

Acute kidney injury

Chronic kidney disease

Haematuria

Pleural effusion

Respiratory failure

Pregnancy of partner

Hypertensive crisis

Periorbital oedema

Eyelid oedema

Conjunctival haemorrhage

Dry eye

100%

80%

60%

40%

20%

Study treatment Arm

Bosutinib

Imatinib

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: Single Agent BosutinibExperimental Treatment1 Intervention

Bosutinib administered orally once daily in pediatric patients with newly diagnosed chronic phase Ph+ CML (ND CML) and pediatric patients with Ph+CML who have received at least one prior TKI therapy (R/I CML). A treatment cycle is defined as 28 days

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bosutinib

2015

Completed Phase 3

~3040

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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

The most common treatments for Chronic Myeloid Leukemia (CML) are Tyrosine Kinase Inhibitors (TKIs) like Bosutinib. These drugs target the BCR-ABL fusion protein, which is produced by the Philadelphia chromosome abnormality and has abnormal tyrosine kinase activity that drives the proliferation of leukemic cells. By inhibiting this kinase activity, TKIs reduce the growth of these malignant cells, leading to remission in many patients. This targeted approach is crucial for CML patients as it offers a more precise and effective treatment compared to traditional chemotherapies.

Current perspectives on the treatment of patients with chronic myeloid leukemia: an individualized approach to treatment.