Paediatric Strategy Forum for medicinal product development for acute myeloid leukaemia in children and adolescents: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

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.
Competing Interests: Conflict of interest statement PA is an employee of Sanofi. BB is an employee of Celgene. FB is an employee of Servier. AB is an employee of Jazz Pharmaceuticals. RC is an employee of Novartis. DD is an employee of Astellas Pharma Global Development, Inc. DF is an employee of Takeda Pharmaceuticals. LF has participated in advisory boards for Astellas. PGF is an employee of Sanofi. MK is an employee of BMS. SYK is an employee of AbbVie. SM is an employee of Helsinn Healthcare. HM is an employee FORMA Therapeutics. JM is an employee of Amgen. LVM has participated in advisory boards for AstraZeneca, Merck, Tesaro, Bayer and Celgene. JN is an employee, Janssen Research & Development. ADJP has participated in advisory boards for Novartis, Takeda, Merck, Lilly and Celgene. SS is an employee of Roche/Genentech. TW is an employee of Agios Pharmaceuticals. CMZ has received institutional research funding from Pfizer, Daiichi-Sankyo, BMS and Celgene. Consultancy was provided for Agios, Takeda, Janssen, Sanofi, Servier, AbbVie and Forma therapeutics. Travel support was obtained from Jazz Pharmaceuticals.
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