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

June 24, 2022 updated by: Eisai Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • New Lambton Heights, New South Wales, Australia
      • Westmead, New South Wales, Australia
    • Victoria
      • Parkville, Victoria, Australia
    • Western Australia
      • Subiaco, Western Australia, Australia
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
  • United States
    • Arizona
      • Phoenix, Arizona, United States
    • California
      • Madera, California, United States
    • Colorado
      • Aurora, Colorado, United States
    • Florida
      • Miami, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
      • Worcester, Massachusetts, United States
    • Minnesota
      • Rochester, Minnesota, United States
    • New York
      • New Hyde Park, New York, United States
      • New York, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
    • Ohio
      • Columbus, Ohio, United States
    • Oregon
      • Portland, Oregon, United States
    • Texas
      • Dallas, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Washington
      • Seattle, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 16 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

  1. Males and females, age 1 to 16 years, inclusive
  2. Females of childbearing potential must have a negative serum beta human chorionic gonadotropin ( B-hCG) at Visit 1 (Screening) and a negative urine pregnancy test prior to starting study drugs (Visit 2). Female subjects of childbearing potential must agree to be abstinent or to use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, intrauterine devise (IUD), or have a vasectomised partner) for at least one menstrual cycle prior to starting study drug(s) and throughout the Randomization Phase or 30 days after the last dose of study drug. Those females using hormonal contraceptives must also be using an additional approved method of contraception (as described previously)
  3. Sexually mature male patients who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the Randomization Phase and for 30 days (longer if appropriate) after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously)
  4. Diagnosis of acute myelogenous leukemia ( AML) (bone marrow or peripheral blood blasts greater than or equal to 20%)
  5. Adequate cardiac function as defined by an echocardiogram or multiple gated acquisition (MUGA) scan demonstrating an ejection fraction greater than 50%
  6. Are willing and able to comply with all aspects of the protocol
  7. Provide written informed consent from subject's guardian or legally authorized representative and child assent (if applicable).

Exclusion Criteria

  1. Females who are pregnant (positive B-hCG test) or lactating
  2. History of chronic myelogenous leukemia (CML) [t(9;22)]
  3. Acute promyelocytic leukemia (M3 subtype in French-American-British [FAB] classification)
  4. Known central nervous system (CNS) leukemia
  5. AML associated with congenital syndromes such as Down syndrome, Fanconi anemia, Bloom syndrome, Kostmann syndrome, or Diamond-Blackfan anemia
  6. White blood cell (WBC) count greater than 100,000/mm3
  7. Serum creatinine greater than 2.5 mg/dL
  8. Alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN) and/or total bilirubin greater than 3 x ULN
  9. Prior chemotherapy (other than hydroxyurea) or radiation therapy for AML
  10. Known to be human immunodeficiency virus (HIV) positive
  11. Any history of or concomitant medical condition that, in the opinion of the Investigator, would compromise the subject's ability to safely complete the study
  12. The Investigator believes the subject to be medically unfit to receive the study drug or unsuitable for any other reason
  13. Subject with hypersensitivity to decitabine, daunorubicin, cytarabine, or etoposide
  14. Has participated in a drug trial in the last 4 weeks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A
Drug: Decitabine
5 day priming with decitabine followed by Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide).
Drug: Decitabine
Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide) only
Experimental: Arm B
Drug: Decitabine
5 day priming with decitabine followed by Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide).
Drug: Decitabine
Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide) only

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Morphologic Complete Remission (CR)
Time Frame: 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.
Day 50

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
DNA Methylation
Time Frame: 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).
Baseline up to completion of induction therapy (Day 15)
Leukemia-free Survival (LFS)
Time Frame: 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.
Baseline to recurrence of Leukemia or Death (up to 2 years 5 months)
Overall Survival (OS)
Time Frame: 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.
Baseline to Date of Death (up to 2 years 5 months)
Percentage of Participants With Minimal Residual Disease (MRD) at Baseline and Day 50
Time Frame: Baseline and Day 50
After induction chemotherapy, based on bone marrow biopsies. No formal statistical analyses of MRD were performed for this study.
Baseline and Day 50
Time to CR
Time Frame: 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.
Randomization to Day 50
Time to Neutrophil Recovery
Time Frame: 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.
Baseline up to Day 50
Time to Platelet Recovery
Time Frame: 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.
Baseline up to Day 38

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Eisai Medical Services, Eisai Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 3, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 19, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 19, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 5, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 28, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • E7373-G000-202

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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