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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARM A: Conventional Consolidation | Active Comparator | 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) |
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| ARM B: Blocks Therapy | Experimental | 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARM A: Active Comparator Drug | Drug | Consolidation 6-thioguanine 60 mg/m2/d, 1 to 43 po; prednisone 40 mg/m2/d, on days 1-28 orally; vincristine 1.5 mg/m2/d, 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; cyclophosphamide 500 mg/m2/d, days 29, 43. |
| Measure | Description | Time Frame |
|---|---|---|
| Determine if two-cycle consolidation reduced the cumulative incidence of relapse compared to conventional consolidation (CONS) among newly diagnosed pediatric patients with AML. | The GATLA 8-LMA-P'07 was a randomized trial including pediatric AML children in Argentina; the design was based on AML-BFM 98 with minor modifications.(10) Similar to AML-BFM 98, the trial compared two approaches to consolidation. The standard regimen was a 6-week consolidation phase (CONS), which was also used in AML-BFM 93 vs. the comparator regimen of two short chemotherapy cycles (two-cycle) with cytarabine plus idarubicin (AI) and high dose cytarabine plus mitoxantrone (haM). AML-BFM 98 previously demonstrated that haM was tolerable.10 We hypothesized that the two-cycle consolidation (two-cycle) would be associated with lower relapse rates related to dose intensification compared to the standard CONS approach. | 72 months |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate Event-free survival (EFS) of pediatric patients with AML. | EFS was calculated from date of randomization to first event (death, resistant leukemia, relapse or secondary malignancy) or date of last follow-up. | 72 months |
| Evaluate Overall Survival (OS) of pediatric patients with AML. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alcyra Fynn, Dr. | Grupo Argentino de Tratamiento de la Leucemia Aguda | Study Chair |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29550834 | Background | Rasche M, Zimmermann M, Borschel L, Bourquin JP, Dworzak M, Klingebiel T, Lehrnbecher T, Creutzig U, Klusmann JH, Reinhardt D. Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia. 2018 Oct;32(10):2167-2177. doi: 10.1038/s41375-018-0071-7. Epub 2018 Feb 22. | |
| 34811958 |
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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.
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|
| ARM B: Blocks Therapy Drug | Drug | Blocks AI Cytarabine 500 mg/m2 as 24 infusion infusion x 4 d; Idarubicin 7 mg/m2 on days 3 and 5; Intrathecal cytarabine on days 0 and 6. haM Cytarabine 1 g/m2 every 12 hours for 3 days; Mitoxantrone 10 mg/m2 days 4 and 5; Intrathecal cytarabine days 6 and 15. |
|
OS was also calculated from date of randomization to date of death or date of last follow-up. |
| 72 months |
| van Weelderen RE, Njuguna F, Klein K, Mostert S, Langat S, Vik TA, Olbara G, Kipng'etich M, Kaspers GJL. Outcomes of pediatric acute myeloid leukemia treatment in Western Kenya. Cancer Rep (Hoboken). 2022 Oct;5(10):e1576. doi: 10.1002/cnr2.1576. Epub 2021 Nov 22. |
| 26304895 | Background | Zwaan CM, Kolb EA, Reinhardt D, Abrahamsson J, Adachi S, Aplenc R, De Bont ES, De Moerloose B, Dworzak M, Gibson BE, Hasle H, Leverger G, Locatelli F, Ragu C, Ribeiro RC, Rizzari C, Rubnitz JE, Smith OP, Sung L, Tomizawa D, van den Heuvel-Eibrink MM, Creutzig U, Kaspers GJ. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia. J Clin Oncol. 2015 Sep 20;33(27):2949-62. doi: 10.1200/JCO.2015.62.8289. Epub 2015 Aug 24. |
| 23471307 | Background | Sung L, Aplenc R, Alonzo TA, Gerbing RB, Lehrnbecher T, Gamis AS. Effectiveness of supportive care measures to reduce infections in pediatric AML: a report from the Children's Oncology Group. Blood. 2013 May 2;121(18):3573-7. doi: 10.1182/blood-2013-01-476614. Epub 2013 Mar 7. |
| 31384271 | Background | Fedorovsky JM, Cuervo LG, Luciani S. Pediatric cancer registries in Latin America: the case of Argentina's pediatric cancer registry. Rev Panam Salud Publica. 2017 Dec 5;41:e152. doi: 10.26633/RPSP.2017.152. eCollection 2017. |
| 16883600 | Background | Howard SC, Ortiz R, Baez LF, Cabanas R, Barrantes J, Fu L, Pena A, Samudio A, Vizcaino M, Rodriguez-Galindo C, Barr RD, Conter V, Biondi A, Masera G; MISPHO Consortium Writing Committee. Protocol-based treatment for children with cancer in low income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)--part II. Pediatr Blood Cancer. 2007 Apr;48(4):486-90. doi: 10.1002/pbc.20989. |
| 21902686 | Background | Gibson BE, Webb DK, Howman AJ, De Graaf SS, Harrison CJ, Wheatley K; United Kingdom Childhood Leukaemia Working Group and the Dutch Childhood Oncology Group. Results of a randomized trial in children with Acute Myeloid Leukaemia: medical research council AML12 trial. Br J Haematol. 2011 Nov;155(3):366-76. doi: 10.1111/j.1365-2141.2011.08851.x. Epub 2011 Sep 9. |
| 23704089 | Background | Creutzig U, Zimmermann M, Bourquin JP, Dworzak MN, Fleischhack G, Graf N, Klingebiel T, Kremens B, Lehrnbecher T, von Neuhoff C, Ritter J, Sander A, Schrauder A, von Stackelberg A, Stary J, Reinhardt D. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013 Jul 4;122(1):37-43. doi: 10.1182/blood-2013-02-484097. Epub 2013 May 23. |
| 19776406 | Background | Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1249-59. doi: 10.1056/NEJMoa0904544. |
| 16983120 | Background | Creutzig U, Zimmermann M, Lehrnbecher T, Graf N, Hermann J, Niemeyer CM, Reiter A, Ritter J, Dworzak M, Stary J, Reinhardt D. Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98. J Clin Oncol. 2006 Sep 20;24(27):4499-506. doi: 10.1200/JCO.2006.06.5037. |
| 10086807 | Background | Creutzig U, Zimmermann M, Ritter J, Henze G, Graf N, Loffler H, Schellong G. Definition of a standard-risk group in children with AML. Br J Haematol. 1999 Mar;104(3):630-9. doi: 10.1046/j.1365-2141.1999.01304.x. |
| 40367210 | Derived | Deana A, Gomez SM, Fynn AB, Freigeiro D, Riccheri MC, Moran LE, Makiya ML, Sung L. Comparison of Consolidation Strategies for Pediatric Patients With Acute Myeloid Leukemia: Results of the Randomized GATLA 8-LMA-P'07 Trial. J Pediatr Hematol Oncol. 2025 Jul 1;47(5):250-256. doi: 10.1097/MPH.0000000000003028. Epub 2025 May 12. |