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

Phase 2

Terminated

• Conditions: Pediatric Acute Myelogenous Leukemia (AML)
• Interventions: Drug: Decitabine

• Registration Number: NCT01177540
• Lead Sponsor: Eisai Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-08-05
• Study First Submitted QC: 2010-08-05
• Study First Posted: 2010-08-09
• Study Start: 2011-03-03
• Primary Completion: 2013-07-19
• Study Completion: 2013-07-19
• Status Verified: 2013-10
• Results First Submitted: 2022-05-26
• Results First Submitted QC: 2022-06-24
• Last Update Submitted: 2022-06-24
• Results First Posted: 2022-06-28
• Last Update Posted: 2022-06-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Decitabine	-
Arm B	Decitabine	-

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Morphologic Complete Remission (CR)	Day 50	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.

Secondary Outcome Measures

Name	Time	Method
DNA Methylation	Baseline up to completion of induction therapy (Day 15)	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).
Leukemia-free Survival (LFS)	Baseline to recurrence of Leukemia or Death (up to 2 years 5 months)	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.
Overall Survival (OS)	Baseline to Date of Death (up to 2 years 5 months)	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.
Percentage of Participants With Minimal Residual Disease (MRD) at Baseline and Day 50	Baseline and Day 50	After induction chemotherapy, based on bone marrow biopsies. No formal statistical analyses of MRD were performed for this study.
Time to CR	Randomization to Day 50	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 to Neutrophil Recovery	Baseline up to Day 50	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 to Platelet Recovery	Baseline up to Day 38	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.