Table 3.
Overview of Ongoing or Pending Clinical Trials in Newly Diagnosed AML, Including Main Study Questions and Primary End Points
| Group | Years of Accrual | Sample Size, No. of Patients | Age Range, Years | Primary Design and Objective(s) | Primary End Point(s) | Secondary Objectives |
|---|---|---|---|---|---|---|
| AIEOP | 2015-2018 | 250 | 018 | FLADx versus ICE as second induction course for reducing end of induction MRD; FLAMSA in place of autologous SCT in patients with intermediate-risk disease as third consolidation | End of induction BM MRD < 0.1%; LFS | To validate the new stratification criteria (SR, IR, HR); to reduce anthracycline dosage in SR patients; to compare MRD using MDF versus PCR |
| BFM-AML | 2014-2019 | 500 | 0 to < 19 | Random assignment to clofarabine, cytarabine, and DNX versus ADxE in induction I; random assignment to maintenance therapy | EFS of randomly assigned patients; EFS from second random assignment | To implement a molecular and MRD-based risk classification; to assess safety of novel therapies in combination with chemotherapy; o identify early molecular relapse by MRD monitoring in peripheral blood |
| COG | 2010-2016 | 1,050-1,250 | 0 to < 30 | Random assignment: standard MRC-based therapy with or without bortezomib; a nonrandomized stratification of patients positive for FLT3-ITD to chemotherapy plus sorafenib | EFS; OS To assess MRD response with intensification of induction II for patients positive by MRD at the end of induction I; to assess OS, DFS, RR with sorafenib in patients with FLT3-ITD and with best donor allogeneic SCT | |
| JPLSG | 2014-2018 | 300 | 0 to < 19 | Random assignment of high-dose cytarabine induction versus standard-dose cytarabine induction | EFS; MDF BM MRD after initial induction | To improve overall outcome; to achieve similar or decreased early mortality and death in CR1; to improve outcome of molecular subgroups; to compare WT1 transcript MRD versus MDF MRD |
| NCRI-UK and SFCE MyeChild 01 | 2015-2020 | Up to 700 | 0 to < 18 | Random assignment (R1) of mitoxantrone versus DNX in induction; random assignment (R2) of a single dose of GO 3 mg/m2 versus the maximum tolerated number of doses (max 3, as identified by a dose-finding study) combined with induction; random assignment (R3) of HD cytarabine versus FLA in consolidation for patients with SR disease; random assignment (R4) of MAC versus RIC for patients with HR disease undergoing HSCT | R1/2: EFS; R3: RFS; R4: RFS, incidence at day 100 post-transplantation of grade 3-5 toxicity | To compare the predictive value of flow and molecular MRD monitoring for relapse risk |
| NOPHO-DBH AML-2012 | 2013-2019 | 300-350 | 0 to < 19 | Random assignment of DNX versus mitoxantrone in induction I; random assignment of FLADx versus ADxE in induction II | MRD in BM on day 22, course I; MRD in BM on day 22 from start of course II | To estimate survival by MRD-based stratification; to assess early mortality and death in CR1; to compare qPCR for fusion gene transcripts versus MDF in assessment of MRD |
| SJCRH | 2008-2016 | 240 | 0 to < 21 | Random assignment of cytarabine, daunorubicin, and etoposide versus clofarabine and cytarabine in induction | MRD by MDF on day 22 of induction I | To estimate EFS of chemotherapy versus chemotherapy followed by natural killer cell transplantation |
Abbreviations: ADxE, cytarabine, liposomal daunorubicin, and etoposide; AIEOP, Italian Association for Pediatric Hematology and Oncology; BFM, Berlin-Frankfurt-Munster; BM, bone marrow; CIR, cumulative incidence of relapse; COG, Children's Oncology Group; CR1, first complete remission; DBH, Dutch-Belgium-Hong Kong; DFS, disease-free survival; DNX, liposomal daunorubicin; ECM, HD cytarabine, etoposide, and mitoxantrone; EFS, event-free survival; FLA, fludarabine and cytarabine; FLADx, fludarabine, cytarabine, and liposomal daunorubicin; FLAMSA, fludarabine, cytarabine, and amsacrine; GO, gemtuzumab ozogamicin; HD, high dose; HR, high risk; HSCT, hematopoietic stem cell transplantation; ICE, idarubicin, cytarabine, and etoposide; IR, intermediate risk; JPLSG, Japanese Pediatric Leukemia/Lymphoma Study Group; LFS, leukemia-free survival; MAC, myeloablative conditioning; MDF, multidimensional flow cytometry; MRC, Medical Research Council; MRD, minimal residual disease; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NCRI-UK, National Cancer Research Institute-United Kingdom; RIC, reduced intensity conditioning; NOPHO, Nordic Society for Pediatric Hematology and Oncology; OS, overall survival; (q)PCR, (quantitative) polymerase chain reaction; R, response; RFS, relapse-free survival; RR, relapse rate; SCT, stem-cell transplantation; SFCE, Société Française de lutte contre les Cancers et leucémies de l'Enfant et de l'adolescent; SJCRH, St Jude Children's Research Hospital; SR, standard risk; WT1, Wilms tumor 1.