Comparison of Consolidation Strategies for Pediatric Patients With Acute Myeloid Leukemia

NCT06211452 | Completed Phase 3

• 1 other identifier: GATLA 8-AML´07
• Study Type: interventional
• Target: 258
• Locations: 0 countries
• Sites: N/A

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.

Conditions

AML; Pediatric AML

Keywords

AML; Pediatric AML; Randomization

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Evaluate Event-free survival (EFS) of pediatric patients with AML.

  72 months

• Evaluate Overall Survival (OS) of pediatric patients with AML.

  72 months

Study Arms (2)

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)

Drug: ARM A: Active Comparator Drug

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)

Drug: ARM B: Blocks Therapy Drug

Interventions

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.

ARM A: Conventional Consolidation

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.

ARM B: Blocks Therapy

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grupo Argentino de Tratamiento de la Leucemia Aguda: lead

Related Publications (11)

• 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.

  PMID: 29550834 BACKGROUND

• 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.

  PMID: 34811958 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.

  PMID: 26304895 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.

  PMID: 23471307 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.

  PMID: 31384271 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.

  PMID: 16883600 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.

  PMID: 21902686 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.

  PMID: 23704089 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.

  PMID: 19776406 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.

  PMID: 16983120 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.

  PMID: 10086807 BACKGROUND

Study Officials

• Alcyra Fynn, Dr.

  Grupo Argentino de Tratamiento de la Leucemia Aguda

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 18, 2024
• Study Start: August 1, 2007
• Primary Completion: March 15, 2015
• Study Completion: December 21, 2015
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share