Efficacy of Gemtuzumab Ozogamycin for Patients Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): gemtuzumab ozogamycin
Intervention type(s): Drug
Intervention description(s): gemtuzumab ozogamycin = 6mg/m² during the induction course (Day 4) gemtuzumab ozogamycin = 6mg/m² during the first intensive consolidation course (Day 4)
Other intervention name(s): gemtuzumab ozogamycin (MYLOTARG ®)
Intervention MeSH terms: Gemtuzumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: AML; gemtuzumab ozogamycin