The PedAL/EuPAL Project: A Global Initiative to Address the Unmet Medical Needs of Pediatric Patients with Relapsed
Valeria Ceolin1,2, Sae Ishimaru1, Seth E Karol3
1Princess Máxima Center for Pediatric Oncology, 3584 Utrecht, The Netherlands.
Insights
Children with relapsed/refractory acute myeloid leukemia (AML) need better treatments. The Pediatric Acute Leukemia (PedAL) program and European Pediatric Acute Leukemia (EuPAL) collaboration are developing new, targeted therapies for improved survival in pediatric AML patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Trials
Background:
- Prognosis for pediatric acute myeloid leukemia (AML) has improved, but survival at relapse remains poor (40-50%).
- Chemo-refractory disease in children with AML presents a significant therapeutic challenge, necessitating novel and less toxic treatment options.
Purpose of the Study:
- To establish new standards of care for pediatric acute myeloid leukemia (AML) in first and second relapse.
- To utilize biology-based selection markers for treatment stratification in relapsed/refractory pediatric AML.
- To generate crucial data for advancing targeted therapies into front-line pediatric AML studies.
Main Methods:
- The Pediatric Acute Leukemia (PedAL) program, a global initiative, is implemented in Europe as the European Pediatric Acute Leukemia (EuPAL) complex clinical trial.
- Patients are stratified into sub-trials focusing on targeted inhibitors at relapse.
- Harmonized response and safety definitions are employed across all sub-trials for consistent data evaluation.
Main Results:
- The manuscript provides an overview of potential treatment targets in pediatric AML.
- It focuses on drugs planned for inclusion in the PedAL/EuPAL project.
- This collaborative effort aims to identify effective, biology-driven treatments for relapsed/refractory pediatric AML.
Conclusions:
- The PedAL/EuPAL collaboration seeks to improve outcomes for children with relapsed/refractory AML.
- Targeted inhibitors and biology-based stratification are key to developing new standards of care.
- This initiative is vital for advancing pediatric AML treatment and drug development.
Abstract:
The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40-50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed for these children. The Pediatric Acute Leukemia (PedAL) program is a strategic global initiative that aims to overcome the obstacles in treating children with relapsed/refractory acute leukemia and is supported by the Leukemia and Lymphoma Society in collaboration with the Children's Oncology Group, the Innovative Therapies for Children with Cancer consortium, and the European Pediatric Acute Leukemia (EuPAL) foundation, amongst others. In Europe, the study is set up as a complex clinical trial with a stratification approach to allocate patients to sub-trials of targeted inhibitors at relapse and employing harmonized response and safety definitions across sub-trials. The PedAL/EuPAL international collaboration aims to determine new standards of care for AML in a first and second relapse, using biology-based selection markers for treatment stratification, and deliver essential data to move drugs to front-line pediatric AML studies. An overview of potential treatment targets in pediatric AML, focused on drugs that are planned to be included in the PedAL/EuPAL project, is provided in this manuscript.
