Efficacy and Safety of Decitabine as Epigenetic Priming With Induction Chemotherapy in Pediatric Acute Myelogenous Leukemia (AML) Subjects

Disease response measurements were based on bone marrow evaluations (biopsies, aspirates, or both) performed by local pathology laboratories and assessed by study investigators. A designation of CR required that the participant achieve a morphologic leukemia-free state and have an absolute neutrophil count (ANC) greater than 1000 per microliter (/mcL) and a platelet count greater than 100,000/mcL.

Time frame: Day 50

Population: The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response.

Bone marrow samples were obtained at baseline and completion of induction therapy. DNA was extracted, and global DNA methylation was evaluated using the Infinium® Human Methylation450® BeadChip Array according to the manufacturer's protocol (Illumina, San Diego, California). Paired differential methylation analysis of end-induction marrows to participant matched screening marrows was performed to identify differentially methylated cytosines followed by guanine residue (CpG) loci (DML). A paired Wilcoxon rank test was conducted to compare end-induction marrows with diagnostic marrows within each arm to identify loci considered statistically significant and differentially methylated. Three different behaviors were defined: 'hypermethylation' (increased intensity in the tumor), 'hypomethylation' (decreased intensity in the tumor) and 'no change' (no substantial differences of intensity).

Time frame: Baseline up to completion of induction therapy (Day 15)

Population: The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response.

LFS was defined as time from CR until the recurrence of leukemia (greater than or equal to \[\>=\] 5% bone marrow blasts, reappearance of peripheral blasts or the appearance of new dysplastic changes, or death, whichever occurred first). For participants who did not achieve a CR, LFS is set to zero days. For participants with CR who do not have leukemic recurrence or death, data for LFS was censored on the date of the last follow-up bone marrow or hematology examination, whichever is later. LFS was analyzed using Kaplan-Meier method.

Time frame: Baseline to recurrence of Leukemia or Death (up to 2 years 5 months)

Population: The per protocol set included all participants who sufficiently complied with protocol. Here overall number of participants analyzed are participants who achieved morphologic CR and were available for this outcome measure assessment at given time period.

OS was defined as the time from the date of the first dose of study treatment to the date of death from any cause. OS was analyzed using Kaplan-Meier method.

Time frame: Baseline to Date of Death (up to 2 years 5 months)

Population: The per protocol set included all participants who sufficiently complied with protocol.

After induction chemotherapy, based on bone marrow biopsies. No formal statistical analyses of MRD were performed for this study.

Time frame: Baseline and Day 50

Population: The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. Here overall number of participants analyzed are participants who were available for this outcome measure assessment at given time points.

Disease response measurements were based on bone marrow evaluations (biopsies, aspirates, or both) performed by local pathology laboratories an assessed by study investigators. CR: requires that the participant achieved a morphologic leukemia-free state and had an ANC \>1000/mcL and platelets \>100,000/mcL. Hemoglobin concentration or hematocrit had no bearing on remission status, although the participant had to be independent of transfusions. Kaplan-Meier curves were used to describe time to CR.

Time frame: Randomization to Day 50

Population: The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. Here overall number of participants analyzed are participants who achieved morphologic CR and were available for this outcome measure assessment at given time period.

Blood sampling was used to determine recovery, and is defined as less than or equal to 1000 per cubic millimeter (/mm\^3) for absolute neutrophil count (ANC). Summarized using Kaplan-Meier product limit estimators.

Time frame: Baseline up to Day 50

Population: The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. Here overall number of participants analyzed are participants who were available for this outcome measure assessment at given time period.

Blood sampling was used to determine recovery and is defined as less than or equal to 100,000/mm\^3 for platelet count. Summarized using Kaplan-Meier product limit estimators.

Time frame: Baseline up to Day 38

Population: The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response All participants in FAS had platelet recovery.