Clinical trial NCT06211452: Comparison of Consolidation Strategies for Pediatric Patients With Acute Myeloid Leukemia
Official title: Comparison of Consolidation Strategies for Pediatric Patients With Acute Myeloid Leukemia - Results of the Randomized GATLA 8-LMA-P'07 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: AML
Pediatric AML
Keywords: AML
Pediatric AML
Randomization
Lead sponsor: Grupo Argentino de Tratamiento de la Leucemia Aguda
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 258
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: It is a randomized model, the evaluation is based on event time (overall survival, event free survival, cumulative incidence relapse with treatment related mortality as competitive event). Comparator log rank test.
Primary purpose: TREATMENT

Brief summary: GATLA 8-AML´07 trial is an multicenter phase III dose-optimization trial for the treatment of acute myeloid leukemias in children and adolescents. Patients are treated with a combination of intensive chemotherapy in combination with intrathecal-injection by CNS and haematopoietic stem cell transplantation.

The patients are stratified in a standard-group (SR) and a high risk-group (HR). SR was defined as FAB (French-American-British) M1/M2 with Auer rods; FAB M4eo or favorable cytogenetics \[t(8;21)/AML1-ETO or inv(16) or t(16;16) and/or CBFB/MYH11)\]; bone marrow blasts ≤5% on day 15. HR was defined as all others. SR patients were reclassified to the HR group if FLT3-ITD positive.

Based on the experience of the BFM group, it was decided to randomly evaluate whether the six-drug conventional consolidation stage can be replaced with the use of a consolidation based by block therapy on drugs of proven efficacy in AML with the aim of reducing residual disease, and the toxicity of this stage. Patients are randomized once the double induction is completed into those who will receive the conventional consolidation phase and those who will receive consolidation with the combination of high doses cytarabine and two different anthracyclines sequentially.

Detailed description: All patients in the trial, whether standard risk (SR) or high risk (HR), receive 2 Induction courses: AIE and HAM and then are randomized to continue with the consolidation phase: a conventional consolidation (Arm A) with 6 drugs vs 2 blocks of chemotherapy that are incorporated in this protocol (AI and haM) (Arm B) and then an Intensification phase with high doses of cytarabine and etoposide. The difference between the SR and AR groups is that the former don't continue with the maintenance phase, while those in HR receive 1 year of Maintenance if they don't have a histoidentical family donor. SR patients according to cytogenetics and with \< 5% blasts in the bone marrow on day 15, haven´t indication for TCHP in 1st CR. HR patients, with a histoidentical family donor, will be transplanted in the 1st. CR after the Consolidation phases or the AI and haM blocks, according to the treatment arm that corresponded to them by randomization

Eligibility criteria: Inclusion Criteria:

* De novo AML
* FAB M0-M7
* Primary myelosarcomas or acute mixed lineage leukemia / biphenotypic leukemia (predominantly myeloid).
* Written informed consent from patients, parents, or guardians was obtained at study entry in accordance with the Declaration of Helsinki

Exclusion Criteria:

* AML as secondary malignancy
* Children with Down's syndrome
* Accompanying diseases which do not allow therapy according to the protocol
* Pre-treatment for more than 14 days with another intensive induction therapy
* Patients with APL
* Patients with myelodysplasia
* Patients with blast crisis of Chronic Myeloid Leukemia
* Patients who die before starting treatment

Primary outcomes:
measure: Determine if two-cycle consolidation reduced the cumulative incidence of relapse compared to conventional consolidation (CONS) among newly diagnosed pediatric patients with AML.
timeFrame: 72 months
Secondary outcomes:
measure: Evaluate Event-free survival (EFS) of pediatric patients with AML.
timeFrame: 72 months
measure: Evaluate Overall Survival (OS) of pediatric patients with AML.
timeFrame: 72 months
Other outcomes:
Locations:
Study officials:
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Alcyra Fynn, Dr.
role: STUDY_CHAIR
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