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.