Who can enter
- Children and adolescents with acute myeloid leukemia (AML) who show an increase in the small number of leftover leukemic cells (minimal residual disease), indicating that the disease has returned (molecular relapse).
- Age: 3 months up to 21 years.
Goal
The goal of this study is to see which dose of the drug azacitidine is safe and effective in children with a molecular relapse. In addition we will determine whether children respond to the treatment and what side effects can occur due to the treatment. We will also evaluate the quality of life after the treatment.
Background
Approximately one quarter of children with AML relapse after cessation of the chemotherapy. Therefore, they are regularly monitored by their doctor. In about 40-50% of children with AML it is technically feasible to detect very small amounts of leftover leukemic cells in the blood (this is called minimal residual disease or MRD). An increase in this level possibly indicates that the disease has returned, a so-called molecular relapse.
These children usually only receive further treatment when more than 5% leukemic cells are detected in the blood or bone marrow. They are then treated with intensive chemotherapy, most often followed by a stem cell transplantation. In this study children with a molecular relapse will be treated earlier with a low dose of azacitidine. Hopefully, this stabilizes or sufficiently decreases the amount of leftover leukemic cells, so no or less chemotherapy is needed before a stem cell transplantation can take place.
Azacitidine is a drug that has been available for a long time. In high doses it acts like chemotherapy, causing damage to cancer cells but also to normal cells. However, in this study we will use lower doses of azacitidine, thought to have a different mode of action. In cancer cells certain growth inhibiting genes are switched off. A low dose of azacitidine might be able to switch these genes on again, so that cancer cell growth can be inhibited.
Azacitidine has not yet been registered as a drug for the treatment of AML in children and adolescents. Azacitidine has been registered in Europe for the treatment of adults with AML and low numbers of leukemic cells, and for adults with myelodysplastic syndrome, a precursor of AML. In this study we evaluate the safety and efficacy of low dose azacitidine in children and adolescents with a molecular relapse.