Clinical trial NCT00860639: Efficacy of Gemtuzumab Ozogamycin for Patients Presenting an Acute Myeloid Leukemia (AML) With Intermediate Risk
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: AML
gemtuzumab ozogamycin
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Chugai Pharmaceutical
name: French Innovative Leukemia Organisation
First posted: 2009-03-12
Enrollment: 327
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Adult patients with de novo AML and intermediate risk as defined by the cytogenetics criteria of GOELAMS Group:

  * Normal karyotype or
  * Karyotype with other abnormalities, excluding the favourable group \[t (15; 17), t (8; 21), inv (16)\] and the high risk group \[(-5/5q-, -7/7q- , t (9.22), t (6.9), 11q23 anomaly excluding the t (9; 11), abnormal 3q, complex karyotype (\> 3 abnormalities)\]. Not previously treated for AML.
* Patients aged 18 to 60 years
* And having more than 20% of blast cells in bone marrow and as previously described.
* And with intermediate cytogenetics as previously defined
* And whose expression of the CD33 antigen on the blasts was defined using standard method
* And with a WBC \<or equal to 100G/L.
* And who can receive either one or the other of the treatments under study
* And having a good performance status (WHO score \<3) with a life expectancy greater than one month.
* Affiliated with the Social Security

Exclusion Criteria:

* Patients aged under 18 or over 60 years
* OR with AML:

  * Not classifiable in the classification French-American-British (FAB)
  * Type M3
  * Or blastic transformation of a myeloproliferative or myelodysplastic syndrome previously diagnosed
  * Outside the intermediate cytogenetic group as previously defined
* OR with isolated extramedullary localization of their disease
* OR WBC\> 100G / L
* Patients with known human immunodeficiency virus (HIV) infection or human T-lymphotrophic virus 1 (HTLV-1)
* Patients with SGOT/SGPT \>5N
* Patients with a calculated creatinine clearance of \<50 mL/min
* Informed consent refusal
* Pregnant and/or lactating female

Primary outcomes:
measure: event free survival (EFS)after 3 years for patients not eligible for standard allogenic transplantation
timeFrame: 3 years
Secondary outcomes:
measure: 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.
timeFrame: 3 years
Other outcomes:
Locations:
city: Aix
country: France
facility: CH Pays d'Aix
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: CHRU Angers
city: Avignon
country: France
facility: CH Avignon
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Besancon
country: France
facility: CHU Hôpital Minjoz
city: Brest
country: France
facility: CHU Morvan
city: Clermont-Ferrand
country: France
facility: CHU Hôtel Dieu
city: Colmar
country: France
facility: CH Louis Pasteur
city: Dijon
country: France
facility: CHU du Bocage
city: Grenoble
country: France
facility: CHU Michallon
city: Limoges
country: France
facility: CHU Dupuytren
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Metz
country: France
facility: CH Metz Thionvile
city: Montpellier
country: France
facility: CHU Lapeyronie
city: Mulhouse
country: France
facility: CH Muller
city: Nantes
country: France
facility: CHU Hôtel Dieu
city: Nimes
country: France
facility: CHU Carémeau
city: Orléans
country: France
facility: CH La Source
city: Paris
country: France
facility: Hopital Cochin (AP-HP)
city: Pessac
country: France
facility: CHU du Haut Lévèque
city: Poitiers
country: France
facility: CHU Jean Bernard - La Milétrie
city: Reims
country: France
facility: CHU Robert Debré
city: Rennes
country: France
facility: CHU Pontchaillou
city: Saint Etienne
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: CHU Hautepierre
city: Toulouse
country: France
facility: CHU Purpan
city: Tours
country: France
facility: CHU Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: CHU Brabois
Study officials:
affiliation: Nantes University Hospital
name: Jacques Delaunay, MD
role: PRINCIPAL_INVESTIGATOR
References: