Efficacy of Gemtuzumab Ozogamycin for Patients Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk (LAM2006IR)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Open Phase III Trial Testing Efficacy of Gemtuzumab Ozogamycin (MYLOTARG) Associated to Intensive Chemotherapy for Patients Aged Between 18-60 Years and Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk|
- event free survival (EFS)after 3 years for patients not eligible for standard allogenic transplantation [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Complete Remission Rate (CR) Overall Survival at 3 years Relapse rate at 3 years Toxicity and tolerability of each treatment arm Evaluation of Minimal residual disease by WT1 and NPM1 study at different phases of treatment. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2007|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Active Comparator: gemtuzumab ozogamycin
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.
Drug: gemtuzumab ozogamycin
gemtuzumab ozogamycin = 6mg/m² during the induction course (Day 4) gemtuzumab ozogamycin = 6mg/m² during the first intensive consolidation course (Day 4)
Other Name: gemtuzumab ozogamycin (MYLOTARG ®)
|No Intervention: without Mylotarg|
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.
|CH Pays d'Aix|
|Centre Hospitalier de la Côte Basque|
|CHU Hôpital Minjoz|
|CHU Hôtel Dieu|
|CH Louis Pasteur|
|CHU du Bocage|
|Institut Paoli Calmette|
|CH Metz Thionvile|
|Clinique du Parc|
|CHU Hôtel Dieu|
|CHU Archet 1|
|CH La Source|
|Hopital Cochin (AP-HP)|
|Centre Hospitalier Saint-Jean|
|CHU du Haut Lévèque|
|CHU Jean Bernard - La Milétrie|
|CHU Robert Debré|
|Institut de Cancérologie de la Loire|
|Saint Etienne, France|
|Vandoeuvre Les Nancy, France|
|Principal Investigator:||Jacques Delaunay, MD||Nantes University Hospital|