Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study

Christoph Röllig; Christoph Schliemann; Leo Ruhnke; Lars Fransecky; Björn-Niklas Heydrich; Maher Hanoun; Richard Noppeney; Kerstin Schäfer-Eckart; Knut Wendelin; Jan-Henrik Mikesch; Jan Moritz Middeke; Manja Reimann; Frank Fiebig; Sven Zukunft; Martin Wermke; Hubert Serve; Uwe Platzbecker; Carsten Müller-Tidow; Claudia D Baldus; Martin Bornhäuser

doi:10.1111/bjh.19436

Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study

Br J Haematol. 2024 Jun;204(6):2254-2258. doi: 10.1111/bjh.19436. Epub 2024 Apr 9.

Authors

Christoph Röllig¹, Christoph Schliemann², Leo Ruhnke¹, Lars Fransecky³, Björn-Niklas Heydrich³, Maher Hanoun⁴, Richard Noppeney⁴, Kerstin Schäfer-Eckart⁵, Knut Wendelin⁵, Jan-Henrik Mikesch², Jan Moritz Middeke¹, Manja Reimann¹, Frank Fiebig¹, Sven Zukunft¹, Martin Wermke¹, Hubert Serve⁶, Uwe Platzbecker⁷, Carsten Müller-Tidow⁸, Claudia D Baldus³, Martin Bornhäuser^{1

9}

Affiliations

¹ Department of Internal Medicine I, University Hospital Dresden, TU Dresden, Dresden, Germany.
² Department of Medicine A, University Hospital Münster, Münster, Germany.
³ Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
⁴ Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
⁵ Department of Internal Medicine V, Nuremberg Hospital North, Paracelsus Medical University, Nuremberg, Germany.
⁶ Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany.
⁷ Department of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany.
⁸ Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
⁹ National Center for Tumor Diseases Dresden, Dresden, Germany.

PMID: 38593353
DOI: 10.1111/bjh.19436

Abstract

We conducted a phase I trial in newly diagnosed acute myeloid leukaemia (AML) to investigate the combination of two novel targeted agents, gemtuzumab ozogamicin (GO) and midostaurin, with intensive chemotherapy in FLT3-mutated AML and CBF leukaemia. Three dose levels of midostaurin and one to three sequential doses of 3 mg/m² GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m² GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.

Keywords: AML; gemtuzumab ozogamicin; induction therapy; intensive therapy; midostaurin.

Publication types

Clinical Trial, Phase I

MeSH terms

Adult
Aged
Aminoglycosides / administration & dosage
Aminoglycosides / therapeutic use
Antibodies, Monoclonal, Humanized / administration & dosage
Antibodies, Monoclonal, Humanized / adverse effects
Antibodies, Monoclonal, Humanized / therapeutic use
Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
Antineoplastic Combined Chemotherapy Protocols* / adverse effects
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Female
Gemtuzumab* / administration & dosage
Gemtuzumab* / therapeutic use
Humans
Induction Chemotherapy
Leukemia, Myeloid, Acute* / drug therapy
Male
Middle Aged
Staurosporine* / administration & dosage
Staurosporine* / adverse effects
Staurosporine* / analogs & derivatives
Staurosporine* / therapeutic use
fms-Like Tyrosine Kinase 3 / genetics

Substances

Staurosporine
Gemtuzumab
midostaurin
Antibodies, Monoclonal, Humanized
fms-Like Tyrosine Kinase 3
Aminoglycosides

Abstract

Publication types

MeSH terms

Substances

Grants and funding