Bosutinib (CML)

Active, not recruiting - Results published

Who can enter

• Children with newly diagnosed Ph+ chronic myeloid leukemia (CML) or children with Ph+ CML who failed or insufficiently responded to (resistant) or who did not tolerate (intolerant) at least one prior treatment with a tyrosine kinase inhibitor

• Age: 1-18 years

Goal

The goal of this study is to determine a safe and effective dose of bosutinib in children and teenagers with CML. We will evaluate the side effects caused by the treatment and how the children respond to the treatment. In addition we will determine how much bosutinib ends up in the blood, and how quickly the drug is cleared from the body. This is called pharmacokinetics.

Background

In patients with CML, a specific chromosomal aberration is found in the affected cells: two chromosomes (number 9 and 22) have broken during cell division and have been incorrectly pasted together. The newly formed chromosome, also referred to as the Philadelphia chromosome (Ph), produces a unique protein called BCR-ABL. There are multiple blocking agents that specifically inhibit this new protein product (a tyrosine kinase). These drugs are called tyrosine kinase inhibitors (TKIs).

TKIs are part of the treatment of patients with CML. Examples are imatinib, nilotinib and dasatinib. For some children the current TKIs are no longer suitable, because the disease no longer or insufficiently responds to the treatment, or because they cause too many side effects. Therefore, new drugs are being sought.

Bosutinib is a TKI as well, but in part has different side effects than the drugs mentioned previously. For example, it causes more digestive complaints, like diarrhea, but less musculoskeletal complaints. In addition, experiments in animals have suggested that bosutinib may slow down growth to a lesser extent than the other TKIs.

Bosutinib has been registered in America and Europe for the treatment of adult patients with CML. The efficacy of bosutinib in children is not known. This is the first study in which children and teenagers with CML are treated with bosutinib.

This study is now closed for inclusion. 

Last reviewed

March 20, 2026

The above information is intended as a brief summary only and may not reflect the most up-to-date information. For full details and the current status of a protocol, physicians can contact the Princess Máxima Center directly.

Summary

Chronic myeloid leukemia drug approved in Europe and the US

The drug bosutinib was recently approved by the European Medicines Agency (EMA) for use in children with chronic myeloid leukemia (CML). Earlier, it was also approved by the American Food and Drug Administration (FDA). The required registration study was led by the Trial and Data Center of the Princess Máxima Center and Erasmus MC. When reimbursement status from insurers is also obtained, children with CML can receive the drug bosutinib at diagnosis.

Reduced bone growth

CML is a rare form of blood cancer in children. In the Netherlands, a few children receive this diagnosis every year. The treatment consists of a class of drugs called tyrosine kinase inhibitors (TKIs). These drugs block the growth of the faulty white blood cells. A side effect of existing CML treatment is reduced bone growth – a side effect which strongly affects children with cancer, as it limits their height.

Bosutinib is also a TKI and has been used in adults with CML since 2012. Earlier research in mice showed that this drug impairs length growth less than current drugs. Therefore, researchers from Erasmus MC started a clinical study to investigate the effect of bosutinib in children with CML. When the Princess Máxima Center opened in 2018, the researchers involved moved with it to Utrecht.

Bosutinib: a new option

In the study, which involved 60 children from 67 hospitals in Europe and the United States, bosutinib was found to be similarly effective to other TKIs. Muscle and bone pain were much less common than with other drugs. However, nausea or diarrhea were more common. The comparable effectiveness is important because it allows the choice of a drug with which the child experiences the fewest side effects. This is especially relevant because the treatment often needs to be taken for several years.

Children with CML who are under treatment at the Princess Máxima Center and other European hospitals have access to bosutinib as a treatment immediately upon diagnosis, if reimbursed by the insurer. The approval of bosutinib offers a new treatment option for children with CML, with possibly less impact on their growth and development. The latter is still part of follow-up research, as it requires long-term follow-up.

Prof. Michel Zwaan is a pediatric oncologist, research group leader and co-leads the Trial and Data Center that coordinated the study: 'The approval of bosutinib by the EMA is an important step forward in the care of children with this rare form of cancer. As a pediatric oncologist, I am pleased that we now have an additional treatment option that may better meet the needs of children, with hopefully fewer side effects.'

Collaboration and commitment lead to approval

The approval of bosutinib by the EMA is the result of intensive cooperation between the Princess Máxima Center and Erasmus MC. 'It is very special that an academic clinical study - i.e. not led by a pharmaceutical company - has now led to approval of a drug for children with cancer by the EMA,' says Zwaan. 'It is not often that academic parties coordinate this type of study.'

A committed team in the Trial and Data Center at Máxima set up and coordinated the study: from submission of the study protocol in all countries and inclusion of children, to medical advice during therapy and data collection. The study was conducted in collaboration with the Children's Oncology Group in the United States and was funded by pharmaceutical company Pfizer.

The results of the phase I clinical trial looking at the safety and dosage of bosutinib were published in the Journal of Clinical Oncology.

Would you like to read the scientific publication? Please look here: Brivio E, et al. Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921. J Clin Oncol. 2024 Mar 1;42(7):821-831.