HOVON 156

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

Study treatments

• Arm 1: midostaurin in combination with induction therapy and consolidation therapy followed by one-year maintenance therapy
• Arm 2: gilteritinib in combination with induction therapy and consolidation therapy followed by one-year maintenance therapy

Inclusion criteria

• Age ≥18 years
• Newly diagnosed AML or MDS with excess of blasts-2 (EB2) defined according to WHO criteria (appendix A), with centrally documented FLT3 gene mutation (either TKD or ITD or both). AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related. Patients may have had previous treatment with erythropoiesis stimulating agents (ESA) and/or hypomethylating agents (HMAs) for MDS. ESA and HMAs have to be stopped at least four weeks before registration
• FLT3 mutation as assessed by DNA fragment analysis PCR for FLT3-ITD and sequencing for FLT3-TKD. FLT3-ITD positivity is defined as a FLT3-ITD / FLT3-WT ratio of ≥ 0.05 (5%). FLT3-TKD positivity is defined as a variant allelele frequency (VAF = FLT3 TKD / (FLT3 WT + FLT3 TKD)) ≥ 0.05 (5%))
• Considered to be eligible for intensive chemotherapy
• WHO/ECOG performance status ≤ 2

Exclusion criteria

• Prior chemotherapy for AML or MDS-EB2 (with the exception of ESA and HMA). Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts > 30 x 109/L)
• Acute promyelocytic leukemia (APL) with PML-RARA or one of the other pathognomonic variant fusion genes/chromosome translocations
• Blast crisis after CML
  
  

Participating sites

• ZNA Antwerpen
• AZ Delta