A multicentre, randomized trial in adults with de novo Philadelphia-Chromosome positive acute lymphoblastic leukemia to assess the efficacy of ponatinib versus imatinib in combination with low-intensity chemotherapy, to compare end of therapy with indication for SCT versus TKI, blinatumomab and chemotherapy in optimal responders and to evaluate blinatumomab in suboptimal responders (GMALL-EVOLVE)

Abstract

Introduction Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) is treated as standard of care (SoC) by imatinib based treatment combined with induction and consolidation chemotherapy followed by allogeneic stem cell transplantation (SCT) in first remission. The German Multicenter ALL Study Group for Adult ALL (GMALL) reports about a trial to evaluate the impact of ponatinib based therapy, blinatumomab (blina) treatment for suboptimal responders and the possibility of omission of SoC Allo SCT in optimal responders entitled GMALL-EVOLVE. Methods Herein Imatinib is randomized vs. Ponatinib as frontline treatment combined with chemotherapy, optimal responders also get randomized between SCT and chemo-immunotherapy and suboptimal responders receive immunotherapy before SCT. The trial is registered under the EudraCT number 2022-000760-21. Conclusion This trial will answer several major questions in the treatment of Ph+ALL.