Comparison of Consolidation Strategies for Pediatric Patients With Acute Myeloid Leukemia

Grupo Argentino de Tratamiento de la Leucemia Aguda

Status and phase: Completed; Phase 3

Conditions: AML; Pediatric AML

Treatments: Drug: ARM A: Active Comparator Drug; Drug: ARM B: Blocks Therapy Drug

Study type: Interventional

Funder types: Other

Identifiers

NCT06211452

GATLA 8-AML´07

Details and patient eligibility

About

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.

Full 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

Enrollment: 258 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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258 participants in 2 patient groups

ARM A: Conventional Consolidation

Active Comparator group

Description:

Conventional consolidation (CONS) (active comparator) (6-thioguanine 60 mg/m2/d, on days 1 to 43 orally; prednisone 40 mg/m2/d, on days 1 to 28 orally; vincristine 1.5 mg/m2/d, on days 1, 8, 15, 22; idarubicin 7 mg/m2/d, on days 1, 8, 15, 22; cytarabine 75 mg/m2/d, on days 3-6, 10-13, 17-20, 24-27, 31-34, 38-41; intrathecal cytarabine on days 1, 15, 29, 43 \[age-dependent dose\]; cyclophosphamide 500 mg/m2/d, on days 29, 43)

Treatment:

Drug: ARM A: Active Comparator Drug

ARM B: Blocks Therapy

Experimental group

Description:

Block Therapy: AI block (randomized; cytarabine 500 mg/m2 as continuous infusion ×4 days and idarubicin 7 mg/m2 on days 3 and 5; intrathecal cytarabine on days 0 and 6), haM block (high-dose cytarabine 1 g/m2 every 12 hours for 3 days and mitoxantrone 10 mg/m2 on days 4 and 5, intrathecal cytarabine days 6 and 15)

Treatment:

Drug: ARM B: Blocks Therapy Drug