Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Etoposide

Cytarabine

Decitabine

Daunorubicin

Etoposide phosphate

Antimetabolites

Enzyme Inhibitors

5 day priming with decitabine followed by Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide).

Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide) only

Eisai Medical Services

The purpose of this study is to provide data on the activity of a standard daunorubicin, cytarabine, and etoposide (ADE) induction plus epigenetic priming with decitabine as assessed by standard measures of complete remission (CR), leukemia free survival (LFS) and overall survival (OS), as well as, on minimal residual disease (MRD). It will also provide necessary data on the safety and Pharmacokinetics (PK) of decitabine in pediatric patients that is currently unavailable.

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

A Randomized, Open Label, Multicenter Study to Evaluate the 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.

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).

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.

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.

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

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.

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.

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.

Eisai Inc.

Participants received decitabine 20 mg/m\^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days.

Treatment A: Decitabine + Induction Chemotherapy

Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days.

Treatment B: Induction Chemotherapy Only

Total

1 to less than (<) 2 years

2 to 11 years

12 to 16 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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.

The study was terminated early due to enrollment difficulties and the futility of observing differences in remission rate between treatment arms.

Percentage of Participants With Morphologic Complete Remission (CR)

DNA Methylation

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.

Leukemia-free Survival (LFS)

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

Overall Survival (OS)

At Baseline

At Day 50

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.

Percentage of Participants With Minimal Residual Disease (MRD) at Baseline and Day 50

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.

Time to CR

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.

Time to Neutrophil Recovery

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.

Time to Platelet Recovery

Participants received decitabine 20 milligram per square meter (mg/m\^2) infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days.

Spots Global Cancer Trial Database for Efficacy and Safety of Decitabine as Epigenetic Priming With Induction Chemotherapy in Pediatric Acute Myelogenous Leukemia (AML) Subjects

Trial Identification

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Study Description

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