Who can enter
- Children with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangment
- Age < 1 year at diagnosis
Goal
The goal of this study is to improve outcome compared with historical results of the former Interfant trial (Interfant-06) in infants with KMT2A rearranged ALL.
Background
Children < 1 year of age with acute lymphocytic leukemia (ALL) with a KMT2A gene rearrangement have a poor prognosis. These children need innovative and new therapeutic agents to improve the outcome.
Infants are routinely treated according to the Interfant-21 protocol. The difference with the former protocol (Interfant-06) is that blinatumomab, an immunotherapy, has been added as standard to chemotherapy treatment. Blinatumomab has far fewer side effects than chemotherapy and the results from a small study with this drug are very promising.
In Interfant-21, disease and treatment data will be collected in a database to gain insight into the effect and side effects of the medicines used in this treatment protocol. Body material (blood, bone marrow and liquor) will also be used for research.
The research in the Interfant-21 protocol consists of several parts.
There are three general parts:
- Collection of data on disease, treatment and outcomes in a database
- Storage of body material ("residual material"): blood, bone marrow and cerebrospinal fluid (CSF)
- Treatment with blinatumomab
In addition, there are a number of sub-studies, for which participants can decide for each component whether or not they want to participate:
The dosage of most chemotherapy drugs is adjusted for age. This is because we assume that the absorption, degradation and excretion of these drugs is different than in older children and adults. However, this has not yet been adequately studied.
In this substudy, we will measure the concentration of drugs in the blood. This way we want to investigate to what extent the body of a young child (infant) deals differently with chemotherapy than the body of an older child or adult. We will be looking at a number of commonly used drugs:
- dexamethasone, vincristine and daunorubicin (used in Phase 1 and 5)
- high-dose methotrexate (sometimes used in Phase 4)
- 6-mercaptopurine with low-dose methotrexate (used in Phase 6)
As part of treatment, in the Interfant-21 protocol, children receive chemotherapy targeting the central nervous system (CNS). These drugs are administered with an epidural. The goal is to prevent recurrence of the leukemia in the brain. We know that CNS-targeted therapy is essential to cure leukemia. What we do not know is exactly how much treatment is needed for each individual child.
We would like to investigate whether some children can be cured with less therapy and whether other children need more CNS-targeted therapy. To do this, we need to develop better methods to measure leukemia in the CNS. Currently, we look for leukemia cells in the cerebrospinal fluid (CSF) with a microscope, but this is not accurate enough. In the Goldilocks study, we want to see if we can better measure CNS leukemia with other laboratory tests.
Some children are at risk for neurocognitive problems after treatment for ALL. These are problems with, for example, memory, concentration or speed of thought. However, we do not yet know how much influence the therapy and other factors have on neurocognitive development in young children with ALL.
In this study we will examine whether there is any adverse influence of the treatment on neurocognitive development. And if so, we want to see what factors are important for this. Data from cognitive tests and questionnaires will be linked to clinical data collected during treatment.
In the Interfant-21 protocol, children receive treatment with a particular form of immunotherapy, called blinatumomab. Blinatumomab is an antibody that allows the body's own immune cells (T cells) to bind to the leukemia cells, thereby destroying them.
In a small percentage of patients, blinatumomab does not work adequately. This may be because there are few immune cells (T cells) at the time blinatumomab is given. It could also be due to the influence blinatumomab has on the production of immune cells in the bone marrow. In the sub-study on immune monitoring, we want to see which cells in the blood or bone marrow influence the efficacy of blinatumomab.