Who can enter
- Children and young adults with acute myeloid leukemia (AML) in whom the disease has returned for the first time (relapsed) and who cannot tolerate treatment with anthracyclines, or in whom the disease relapsed for the second time
- Age: from 29 days through 21 years of age
The goal of this study is to investigate whether adding the drug venetoclax to standard chemotherapy leads to improved survival for children and young adults with relapsed AML.
The prognosis of children with AML has improved in recent decades, but outcome after relapse remains insufficient. Most chemotherapy treatments for AML contain anthracyclines (e.g., mitoxantrone or daunorubicin) that can cause heart damage in some children. If their disease relapses, they need other treatment options. Therefore, in this study, we will investigate whether adding venetoclax to anthracycline-free chemotherapy leads to improved survival of children and young adults with relapsed AML.
Venetoclax, in combination with other drugs, is registered (approved) for the treatment of adults with newly diagnosed AML who cannot tolerate intensive chemotherapy. It is also being further studied in adults with relapsed AML. These studies show that the drug works well, is safe and is well tolerated.
Venetoclax is not yet registered for use in children, but several studies in children have been conducted. In those studies, venetoclax has sometimes been studied alone and sometimes in combination with other drugs or treatments, including cytarabine. These studies have shown that adding venetoclax to other treatments is safe and well tolerated. It is possible that the addition of venetoclax could lead to better treatment, but this is still uncertain.
Several chemotherapy combinations have been used in children with relapsed AML, but it is unclear which is the best. The combination of cytarabine, fludarabine (FLA) and gemtuzumab ozogamicin (GO) works well and contains no anthracyclines. Therefore, this combination is used as standard background chemotherapy in this study.
In addition, in half of the patients, venetoclax is added to the chemotherapy. To ensure that the allocation is as fair as possible, this is determined by drawing lots (randomization). This will allow us to compare the efficacy and safety of the chemotherapy, and ultimately survival, with the same chemotherapy combined with venetoclax.