Interfant-21 (ALL)

Clinical study for infants with acute lymphoblastic leukemia with a KMT2A gene rearrangment

Recruiting

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:

Deelonderzoeken

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.

In order to participate in a study please refer to your/your child’s doctor.
For international patients: please feel welcome to contact our International Patients Office.

Last reviewed

May 17, 2023

Study details
Official title
Interfant-21: International collaborative treatment protocol for infants under one year with KMT2A-rearranged acute lymphoblastic leukemia or mixed phenotype acute leukemia
Cancer type
B-cell acute lymphoblastic leukemia with an KMT2A gene rearrangement
Phase
3
Maximum number of patients
160, of whom 12 are expected to participate in the Netherlands
Start date
December 15, 2022
Status
Open
Local principal investigator
Dr. I.M. van der Sluis
Sponsor
Princess Máxima Center for pediatric oncology
Approval
The study of this new treatment has been reviewed by an accredited medical research ethics committee. This committee has decided that it is justified to ask patients to participate in this study. More information can be found at: CCMO.
Trial registry number
Clinicaltrials.gov NCT05327894

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.

Interfant-21 (ALL)

Who can enter

Goal

Background

Deelonderzoeken

4. Sub-study pharmacokinetics (sub-study PATIO)

5. Sub-study on treatment targeting the central nervous system (sub-study Goldilocks)

6. Sub-study neurocognitive development

7. Sub-study immune monitoring

Last reviewed

Study details

Study details