HEM-iSMART is a master protocol with sub-protocols. The overarching objective is that introducing targeted therapy using a biomarker driven approach for treatment stratification may improve the outcome of children with R/R acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) It is characterized by a shared framework that allows for the investigation of multiple IMPs and generate pivotal safety and efficacy evidence within the sub-protocols to establish and define the benefits and risks of new treatments for children with R/R leukemia.~Sub-protocol B within HEM-iSMART, is a phase I/II, multicenter, international, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of dasatinib + venetoclax in combination with dexamethasone, cyclophosphamide and cytarabine in children, adolescents and young with R/R ALL and LBL. Patients with actionable alterations in the MAPK/SRC pathway will be eligible for sub-protocol B including but not limited to NUP214-ABL1 fusion or other ABL1 fusion, activating the kinase domain, or ABL1 amplification, or PDGFRβ-fusion with various fusion partners including but not limited to: AGGF1, DOCK2, SATB1, ETV6 and/or Patients showing a very deep ex-vivo dasatinib IC50 below 10 nM (only data generated in the Zurich Leukemia Research Laboratory Assay will be considered).
HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed/refractory (R/R) ALL and LBL. Sub-protocol B is a phase I/II trial evaluating the safety and efficacy of dasatinib + venetocolax in combination with dexamethasone + Cyclophosphamide and cytarabine in children and AYA with R/R ped ALL/LBL whose tumor present with alterations in the MAPK/SRC pathway.