Efficacy of Gemtuzumab Ozogamycin for Patients Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk

Overview

The main objective of the study is to improve outcome of younger patients (between 18-60 years) with acute myeloid leukemia and intermediate risk defined by the cytogenetics. In this population, in the absence of bone marrow transplantation, event free survival (EFS) is estimated at 35% after three years of follow-up. Adjunction of gemtuzumab ozogamycin (MYLOTARG®) to standard chemotherapy is supposed to increase EFS up to 50% at 3 years. To test this hypothesis, the Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS ) sponsored by Nantes University Hospital leads this randomized open phase III trial in 29 French centers.

Initial randomization will be completed upon receipt of karyotype results and will determine the administration of gemtuzumab ozogamycin (MYLOTARG ®) in combination with chemotherapy during the induction course and the first intensive consolidation course. The induction course include: Daunorubicin for 3 days (60mg/m²) associated with cytarabine (200mg/m²) for 7 days. The MYLOTARG ® will be administered according to the randomization arm on the 4th day of treatment by slow intravenous infusion of 2 hours at a dose of 6 mg/m2. Early bone marrow assessment will be performed at D15. In case of blast excess (\>5%) , a second course of induction will be administered. The consolidation treatment depends on age, molecular prognostic factors, and donor availability: * Patients with good molecular prognosis profile \[ NPM1 + / FLT3 ITD - or CEBPa mutated \] will be consolidated by two courses of intensive chemotherapy comprising Mitoxanthrone and intermediate dose of Cytarabine with or without MYLOTARG ® according to the initial randomization during the first course. * Patients younger than 51 years, eligible for standard allogeneic transplantation with sibling or full matched unrelated donor will receive a standard bone marrow transplantation which not begin before 90 days after the induction. * Patients with no donor or older than 50 years, or with a donor being identified, will receive two courses of intensive consolidation comprising Mitoxantrone and intermediate-dose of Cytarabine with or without Mylotarg ® 6 mg / m² during the first consolidation according to the randomisation arm. * Patients aged 51 to 60 years with an HLA identical donor (sibling or unrelated), will receive a non-myeloablative haematopoietic stem cells transplant (HSCT) after the second course of consolidation. * For other patients, an autologous hematopoietic stem cells transplant (HSCT) will be performed after the 2nd course of consolidation. Collection of peripheral blood stem cells (PBSCs) will be performed after the first consolidation course and a second collection may be considered after the second consolidation course in case of inadequate collection.