APAL2020SC: Pediatric Acute Leukemia (PedAL) Screening Trial # Developing New Therapies for Relapsed Leukemias

Therapeutic options for relapsed acute myeloid leukemia (AML) and some subsets of relapsed acute lymphoblastic leukemia (ALL) remain limited. Various re-induction regimens studied over the last decade have failed to improve our approach to relapsed AML.1, 2 Conventional approaches to improving survival following relapse in AML, and in many patients with ALL, are failing. Recent large-scale discovery efforts using next generation sequencing methods have identified recurrent mutational, signaling pathway and cell surface antigen targets for new therapies. Of those recently approved, some have strong rationale for testing in pediatric patients. However, given the clinical and biologic differences between adult and pediatric AML, significant improvement in survival of children with AML cannot be accomplished if we rely exclusively on approved adult AML drugs for pediatric development.3, 4 The logistical barriers to studying new therapies for uncommon events in rare diseases in children are significant. Many of the high value targets in children (mesothelin, KMT2A, CD56, FLT3) are present in small subsets of patients, and this screening trial represents a mechanism by which we can efficiently interrogate agents in subsets of children with relapsed and refractory acute leukemias. While CAR-T therapy has shifted the paradigm for patients with ALL, relapse post CAR-T is challenging to treat. Identification of new targets in ALL will enable the development of specific therapies for relapse. The Leukemia & Lymphoma Society (LLS) Pediatric Acute Leukemia (PedAL) Screening Protocol will be conducted under a single IND sponsored by LLS and implemented through the Children’s Oncology Group (COG). APAL2020SC will provide a single portal of entry with longitudinal collection of clinical, immunophenotype and molecular data for all children with relapsed/refractory leukemia. This trial will provide a mechanism for target detection and increased efficiency for sub-trial activation. This screening trial will improve new agent availability for children, as well provide efficient pathway for our pharma partners to fulfill regulatory requirements and drug approval.