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

Acute Myeloblastic Leukemia Clinical Trial

Official title: 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)

Status Completed

Clinical Trial Summary

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).

Clinical Trial Description

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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloblastic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

• NCT number: NCT01041040
• Study type: Interventional
• Source: PETHEMA Foundation
• Status: Completed
• Phase: Phase 4
• Start date: October 2007
• Completion date: January 2013