MidOStaurin + Gemtuzumab OzogAmIcin Combination in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
This phase I/II clinical trial evaluates the safety and efficacy of the combined administration of midostaurin and gemtuzumab ozogamicin in the frame of first-line standard chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients displaying a cytogenetic aberration or fusion transcript in the core-binding factor (CBF) genes or FMS-like tyrosine Kinase 3 (FLT3) mutation.
• Written informed consent
• Newly diagnosed AML according to the criteria of the World Health Organisation plus the following molecular or cytogenetic specifications:
‣ Phase I Trial - MODULE:
• t(8;21)/RUNX1-RUNX1T1 or
∙ inv(16) or t(16;16)/CBFB-MYH11 or
∙ FLT3-ITD or
∙ FLT3-tyrosine kinase domain (FLT3-TKD)
⁃ Phase II Trial - MAGNOLIA
• t(8;21)/RUNX1-RUNX1T1 or
∙ inv(16) or t(16;16)/CBFB-MYH11
⁃ Phase II Trial - MAGMA
• FLT3-ITD or
∙ FLT3-TKD
∙ Absence of mutations in CBF genes (i.e. t(8;21)/RUNX1-RUNX1T1 or inv(16) or t(16;16)/CBFB-MYH11)
• Male and female patients aged
‣ 18 - ≤ 75 years in Phase I Trial - MODULE
⁃ 18 - ≤ 70 years in Phase II Trials - MAGMA and MAGNOLIA
• Eastern Cooperative Oncology Group (ECOG) Score of 0-2
• Life expectancy \> 14 days
• Adequate hepatic and renal function
‣ alanine aminotransferase / aspartate transaminase ≤ 2.5 x ULN
⁃ Bilirubin \< 2 x upper limits of normal
⁃ Creatinine \< 1.5 x upper limits of normal or Creatinine clearance \> 40 ml/min
• White blood cell count \< 30 × 10\^9/L. Note: Hydroxyurea and/or a dose of 100-200 mg/m\^2 cytarabine per day for up to 3 days (for emergency use for clinical stabilization) is permitted to meet this criterion.