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
18 Years
60 Years
Both
Acute Myeloid Leukemia
Trial Information
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
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.
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
- 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
event free survival (EFS)after 3 years for patients not eligible for standard allogenic transplantation
Outcome Time Frame:
3 years
Safety Issue:
Yes
Principal Investigator
Jacques Delaunay, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Nantes University Hospital
Authority:
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study ID:
BRD 06/10-I
NCT ID:
NCT00860639
Start Date:
October 2007
Completion Date:
October 2016
Related Keywords:
- Acute Myeloid Leukemia
- AML
- gemtuzumab ozogamycin
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
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