HEM-iSMART is an international clinical trial, co-funded by Imagine for Margo, aimed at improving the treatment of refractory pediatric malignant leukemia and lymphoma.
Childhood Leukemias
Leukemia in children is similar to that in adults but can have certain peculiarities. Acute leukemia is a type of cancer characterized by the spread of cancerous cells originating from bone marrow stem cells.
These cells multiply uncontrollably, invade the bone marrow, and enter the bloodstream, allowing them to spread throughout the body. This proliferation hinders the production of all blood cells (white and red blood cells, platelets). As of 2023, this disease is the most common cancer in children, accounting for about 30% of pediatric cancer cases.
The two main types in children are acute lymphoblastic leukemia (80% of cases) and acute myeloid leukemia. The exact causes of childhood leukemia are not always clearly defined but are thought to be related to genetic and environmental factors or a combination of certain events occurring in the bone marrow stem cells.
About HEM-iSMART
HEM-iSMART is a personalized medicine trial in which children with relapsed leukemia or lymphoma will receive treatment tailored to the specific genetic alterations present in their tumor.
Despite major advances, high-risk patients who are refractory to standard therapy or suffer from relapse still face a very grim prognosis, with a survival rate of only 27%. Ongoing research in cancer genetics and the rapid development of new techniques to analyze tumor material have facilitated the development of drugs that specifically target the mutated proteins resulting from specific genetic alterations. These altered proteins promote cancer development and progression and can lead to tumor cell resistance to standard treatments.
Targeted drugs could reverse the activity of the altered proteins, stop cancer growth, or induce tumor cell death, thereby increasing the survival rate of children with relapsed leukemia or lymphoma.
The HEM-iSMART trial aims to test four different new therapies, each corresponding to a specific genetic alteration present in the patients’ tumors. This new approach, the first to address this issue at the European level, will be carried out in collaboration with the International Leukemia Target Board (ILTB).
This trial includes 4 groups where patients will receive different treatments according to the identified alterations (104 patients, 26 in each group):
- Group A: Decitabine, Venetoclax, and Navitoclax (generic intervention)
- Group B: Dasatinib, Venetoclax, Dexamethasone (alteration: ABL-like)
- Group C: Ruxolitinib, Venetoclax, Dexamethasone (alteration: IL7R and JAK-STAT)
- Group D: Trametinib, Dexamethasone (MAPK pathway alteration)
- *Cyclophosphamide and cytarabine are also added in groups B, C, and D.
Project Progress
The first center (in the Netherlands) has been opened, and the database that will compile all patient results has been created. Additionally, the first contracts with pharmaceutical companies, allowing access to the drugs for this trial, have been signed.
Summary of the HEM-iSMART Project
- Lead Investigators: Prof. Michel C.M. Zwaan
- Program Duration: January 2023 – January 2026
- Number of patients:
- Countries Involved: Netherlands, Germany, Belgium, France, Switzerland, Israel
- Funding by Fight Kids Cancer: €1,498,850, including funding by Imagine for Margo: €849,488
