Treatment resistance and high morbidity associated with conventional chemotherapeutic treatments ask for new therapeutic approaches for relapsed acute lymphoblastic leukemia (ALL). To explore novel treatment options we set up the collaborative research project “Functional modeling of molecular based treatment approaches in relapsed acute lymphoblastic leukemia”. Most important achievements within this research project were the establishment a RNAseq pipeline for the comprehensive molecular characterization of relapsed ALL in conjunction with the setup of mouse and zebrafish models for drug response prediction. This allowed us demonstrate the synergistic effect of two new drugs (Venetoclax and CX-4945) for the treatment of relapsed ALL. These data and models, which were generated within this DKTK project will be clinically applied in future trials for resistant relapsed ALL, such as the international Hem-Smart Trial for pediatric malignancies.The consortium focussed on clinical translation and data exchange within the infrastructure of the German Multicenter Study Group for Adult ALL (GMALL) between research groups were newly established and thereby the essential translational infrastructure of the study group was optimized. Overall three proposals for clinical trials were prepared and submitted to pharmaceutical companies: Venetoclax, Ponatinib and a CD38 antibody. The trial with Ponatinib in Ph+ ALL already received IRB approval. The trial with Venetoclax is short before contract signature. The trial with the CD38 antibody was cancelled due to lack of efficacy of the antibody.