Trial Information

PETHEMA LAM07: Prospective, Multicenter, Uncontrolled Cohort Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)

Patients will be stratified according to age in a first step, with a cut-point of 65 years
old. For patients younger than 65 years old who achieve complete response, a second
stratification will be made before first consolidation treatment. This second stratification
will be performed according to the follow parameters: MDR at the end of induction, karyotype
and molecular findings, including FLT3 internal tandem duplication (ITD) and NPM1 mutations.
The following groups can be identified according to these parameters:

Group A:

Patients aged 65 or younger who are candidates for intensive chemotherapy.

Group A1:

Patients who are in first CR with negative MRD (less than 0.1%), good prognosis karyotype
and, in the case of t(8;21) or inv(16), absence of mutations in the exon 17 of c-kit.

Group A2:

Patients who are in first CR with negative MRD (less than 0.1%), intermediate-risk
karyotype, NPM1 positive and FLT3 negative.

Group A3:

Patients who are in first CR with negative MRD (less than 0.1%), intermediate-risk
karyotype, absence of NPM1 mutations and who are negative for FLT3-ITD or FLT3-ITD positive
with a ratio less than 0.8, regardless NPM1 status.

Group A4:

Patients who are in first CR with positive MRD (greater than 0.1%), t(8;21) or inv(16) with
mutations in the exon 17 of c-kit, intermediate risk karyotype with positive FLT3-ITD and
ratio greater or equal to 0.8 or high-risk karyotype.

Group B:

Patients over 65 years who are able to receive intensive chemotherapy.

TREATMENT SCHEDULE:

Treatment is tailored for each of the previously defined groups:

Group A:

Induction with Idarubicin and ARA-C in "3 +7" schedule (IDA 12 mg/m2 x 3 days and ARA-C 200
mg/m2 x 7 days).

Group A1:

Two consolidation cycles with ARA-C at a dose of 3 g/m2 on days 1, 3 and 5. Collection of
peripheral blood stem cells (PBSC) after the first consolidation. Autologous stem cell
transplantation (ASCT) with Busulphan 1 mg/kg/6 VO or 0,8 mg/kg/6 h IV (Busilvex®) from day
-8 to -5; Etoposide 20 mg/kg/d from day -4 to -3 and ARA-C 3 g/m2/12 h from on days -3 and
-2 (see criteria for HiDAC modification); and G-CSF 10 µg/kg/d from day -9 to -2 (BEA
schedule). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not recommended
in first CR in this group of patients.

Group A2:

First consolidation with Idarubicin and ARA-C at the same dose than induction plus GO 3
mg/m2 at day 1. Collection of PBSC after first consolidation. Second consolidation with
ARA-C 3 g/m2 on days 1, 3 and 5 followed by ASCT with BEA conditioning. It is not
recommended to perform Allo-HSCT, especially from alternative donors, in first CR.

Group A3:

First consolidation with Ida and ARA-C at the same dose than induction plus GO 3 mg/m2 at
day 1. Collection of PBSC after first consolidation. Second consolidation with ARA-C 3 g/m2
on days 1, 3 and 5 followed by ASCT with BEA schedule if no HLA-identical sibling is
available. Patients in this group are candidates for allo-HSCT in first CR if HLA-identical
sibling is available. Allo-HSCT will be performed after first consolidation.

Group A4:

First consolidation with Ida and ARA-C at the same dose than induction plus GO 3 mg/m2 at
day 1. Collection of PBSC after first consolidation. Second consolidation with ARA-C 3 g/m2
on days 1, 3 and 5 followed by ASCT with BEA schedule if no donor is available. Patients in
this group are candidates for allo-HSCT in first CR, including alternative donors. Allo-HSCT
will be performed after first consolidation or later if no donor is available at this time.

Group C:

Induction with Idarubicin and ARA-C "2 + 5" (IDA 12 mg/m2 x 2 days and ARA-C 200 mg/m2 x 5
days). Two consolidations with GO 3 mg/m2 day 1 and ARA-C 100 mg/m2 continuous infusion days
1 to 5.

AML CHARACTERIZATION AND SAMPLES COLLECTION:

To achieve a complete characterization of AML, inmunophenotype analysis (defining the
pattern for MRD studies), cytogenetics, FISH for inv(16), t(8;21) and t(15;17), and
molecular study for AML1/ETO, CBFβ/MYH11, NPM1 and FLT3-ITD will be performed in all cases.
For FLT3-ITD, the ratio between the mutated and not mutated allele will be calculated.

During the phase of samples collection, DNA, RNA and viable cells will be stored.