A Multicentre, Randomized Trial in Adults with de novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia to Assess the Efficacy of Ponatinib versus Imatinib in Combination with Low-Intensity Chemotherapy, to Compare End of Therapy with Indication for Stem Cell Transplantation versus Tyrosine Kinase Inhibitor, Blinatumomab, and Chemotherapy in Optimal Responders, and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

Fabian Lang; Heike Pfeifer; Monika Brüggemann; Eva Hermann; Hubert Serve; Nicola Goekbuget

doi:10.1159/000539391

A Multicentre, Randomized Trial in Adults with de novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia to Assess the Efficacy of Ponatinib versus Imatinib in Combination with Low-Intensity Chemotherapy, to Compare End of Therapy with Indication for Stem Cell Transplantation versus Tyrosine Kinase Inhibitor, Blinatumomab, and Chemotherapy in Optimal Responders, and to Evaluate Blinatumomab in Suboptimal Responders (GMALL-EVOLVE)

Oncol Res Treat. 2024;47(9):430-433. doi: 10.1159/000539391. Epub 2024 May 16.

Authors

Fabian Lang¹, Heike Pfeifer¹, Monika Brüggemann², Eva Hermann³, Hubert Serve¹, Nicola Goekbuget¹

Affiliations

¹ Department of Medicine, Hematology/Oncology, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.
² Department of Hematology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
³ Institute of Biostatistics and Mathematical Modelling, Goethe University Frankfurt, Frankfurt, Germany.

Abstract

Introduction: Philadelphia chromosome-positive acute lymphoblastic leukaemia (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 treatment for suboptimal responders, and the possibility of omission of SoC Allo SCT in optimal responders entitled GMALL-EVOLVE.

Methods: Herein, imatinib is randomized versus 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.

Keywords: Acute lymphoblastic leukaemia; BCR:ABL1; Blinatumomab; Ponatinib.

Publication types

Multicenter Study
Randomized Controlled Trial
Comparative Study
Clinical Trial Protocol

MeSH terms

Adult
Antibodies, Bispecific* / therapeutic use
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Female
Hematopoietic Stem Cell Transplantation / methods
Humans
Imatinib Mesylate* / therapeutic use
Imidazoles* / therapeutic use
Male
Middle Aged
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
Protein Kinase Inhibitors / therapeutic use
Pyridazines* / therapeutic use
Stem Cell Transplantation
Treatment Outcome
Tyrosine Kinase Inhibitors
Young Adult

Substances

ponatinib
Antibodies, Bispecific
Pyridazines
Imidazoles
blinatumomab
Imatinib Mesylate
Protein Kinase Inhibitors
Tyrosine Kinase Inhibitors

Grants and funding

The trial is funded by the Bundesministerium für Bildung und Forschung (BMBF) under the Grant No. 01KG2121. The trial is supported by the following drug supply: ponatinib will be supplied by Incyte Pharmaceuticals, and blinatumomab will be supplied by Amgen Pharmaceuticals.