Andrew D J Pearson1, C Michel Zwaan2, E Anders Kolb3, Dominik Karres4, Julie Guillot5, Su Young Kim6, Lynley Marshall7, Sarah K Tasian8, Malcolm Smith9, Todd Cooper10, Peter C Adamson11, Elly Barry12, Bouchra Benettaib13, Florence Binlich14, Anne Borgman15, Erica Brivio2, Renaud Capdeville16, David Delgado17, Douglas Faller18, Linda Fogelstrand19, Paula Goodman Fraenkel20, Henrik Hasle21, Delphine Heenen22, Gertjan Kaspers2, Mark Kieran23, Jan-Henning Klusmann24, Giovanni Lesa4, Franca Ligas4, Silvia Mappa25, Hesham Mohamed26, Andrew Moore27, Joan Morris28, Kerri Nottage29, Dirk Reinhardt30, Nicole Scobie31, Stephen Simko32, Thomas Winkler33, Koen Norga34, Gregory Reaman35, Gilles Vassal36. 1. ACCELERATE/ITCC, Belgium. Electronic address: andy1pearson@btinternet.com. 2. Princess Máxima Center, Utrecht, the Netherlands; Erasmus MC, Rotterdam, the Netherlands; ITCC, the Netherlands. 3. Nemours/Alfred I. duPont Hospital for Children, USA. 4. European Medicines Agency, Amsterdam, the Netherlands. 5. Fred Hutchinson Cancer Research Center, Leukaemia Lymphoma Society, Target Paediatric AML, USA. 6. AbbVie, USA. 7. Royal Marsden Hospital, The Institute of Cancer Research, UK. 8. Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, USA. 9. National Institutes of Health, National Cancer Institute, USA. 10. Seattle Children's Hospital, USA. 11. Sanofi US, Emeritus Professor of Paediatrics & Pharmacology, Perelman School of Medicine, University of Pennsylvania, USA. 12. Pfizer, USA. 13. Celgene, USA. 14. Servier, USA. 15. Jazz Pharmaceuticals, USA. 16. Novartis Pharma, Switzerland. 17. Astellas Pharma Global Development, Inc., USA. 18. Takeda Pharmaceuticals, USA. 19. Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. 20. Sanofi Genzyme, USA. 21. Department of Paediatrics, Aarhus University Hospital, Denmark. 22. KickCancer, Belgium. 23. BMS, USA. 24. Martin Luther University Halle-Wittenberg, Germany. 25. Helsinn Healthcare, USA. 26. FORMA Therapeutics, USA. 27. Queensland Children's Hospital, Brisbane, Australia. 28. Amgen, USA. 29. Janssen Research & Development, USA. 30. University Hospital Essen, Germany. 31. Zoé4life/CCI, Denmark. 32. Roche/Genentech, Switzerland. 33. Agios Pharmaceuticals, USA. 34. Universitair Ziekenhuis Antwerpen, FAMHP, Belgium. 35. Food and Drug Administration, USA. 36. ACCELERATE/ITCC, Belgium; Gustave Roussy Cancer Centre, France.
Abstract
PURPOSE: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. METHODS: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. RESULTS: CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. CONCLUSION: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes.
PURPOSE: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. METHODS: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. RESULTS:CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. CONCLUSION: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes.
Authors: Sonali P Barwe; Anne Kisielewski; Ezio Bonvini; John Muth; Jan Davidson-Moncada; Edward Anders Kolb; Anilkumar Gopalakrishnapillai Journal: J Clin Med Date: 2022-02-28 Impact factor: 4.241
Authors: Elena Varotto; Eleonora Munaretto; Francesca Stefanachi; Fiammetta Della Torre; Barbara Buldini Journal: Front Pediatr Date: 2022-09-28 Impact factor: 3.569