A Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy — HOVON 156 AML  

Acute Myeloid Leukemia Clinical Trial

Official title: A Phase 3, Multicenter, Open-label, Randomized, Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes With Excess Blasts-2 (MDS-EB2) With FLT3 Mutations Eligible for Intensive Chemotherapy (HOVON 156 AML / AMLSG 28-18)

Status Active, not recruiting

Clinical Trial Summary

Activating mutations in the fms like tyrosine kinase 3 (FLT3) gene are observed in approximately 30% of patients with newly diagnosed acute myeloid leukemia (AML). Addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy prolongs event-free survival (EFS) and overall survival (OS) in patients with a FLT3 mutation. Gilteritinib is a more potent and more specific inhibitor of mutant FLT3 in comparison to midostaurin and has shown promising clinical activity in AML.

Clinical Trial Description

AML and MDS-EB2 are malignant diseases of the bone marrow. The standard treatment for these diseases is chemotherapy. A subgroup of these diseases is characterized by a specific error in the DNA of the leukemic cells. This is the FLT3 mutation, which leads to a change of a certain protein (FLT3) on the blasts. This altered protein plays an important role in the development of leukemia and the survival of leukemic cells.

FLT3 can be inhibited by the drug midostaurin. Adding midostaurin to chemotherapy leads to better treatment results in patients with AML. Therefore, the standard treatment for AML or MDS-EB2 with a FLT3 mutation (FLT3-AML) is a combination of chemotherapy and midostaurin.

Gilteritinib is also a drug that inhibits FLT3. In laboratory studies, gilteritinib was found to be significantly more specific and potent than midostaurin in inhibiting FLT3.

Gilteritinib has subsequently been studied in patients with AML, who relapsed after previous treatment with chemotherapy. This resulted in a much larger number of complete remissions than previously seen when comparable patients were treated with midostaurin. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Anemia, Refractory, with Excess of Blasts
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome With Excess Blasts-2
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

• NCT number: NCT04027309
• Study type: Interventional
• Source: Stichting Hemato-Oncologie voor Volwassenen Nederland
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 20, 2019
• Completion date: June 2033