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Pediatric Acute Myelogenous Leukemia (AML)Phase 2NCT01177540

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

A Phase 2 study testing Decitabine in people with Pediatric Acute Myelogenous Leukemia (AML), run by Eisai Inc. at 22 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 1 year to 16 years
What is being tested?
Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
22 sitesin 3 countries
Study dates
3 Mar 2011to 19 Jul 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Males and females, age 1 to 16 years, inclusive
  • 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)
  • 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)
  • Diagnosis of acute myelogenous leukemia ( AML) (bone marrow or peripheral blood blasts greater than or equal to 20%)
  • Adequate cardiac function as defined by an echocardiogram or multiple gated acquisition (MUGA) scan demonstrating an ejection fraction greater than 50%
  • Are willing and able to comply with all aspects of the protocol
  • Provide written informed consent from subject's guardian or legally authorized representative and child assent (if applicable).

Who cannot join

  • Females who are pregnant (positive B-hCG test) or lactating
  • History of chronic myelogenous leukemia (CML) [t(9;22)]
  • Acute promyelocytic leukemia (M3 subtype in French-American-British [FAB] classification)
  • Known central nervous system (CNS) leukemia
  • AML associated with congenital syndromes such as Down syndrome, Fanconi anemia, Bloom syndrome, Kostmann syndrome, or Diamond-Blackfan anemia
  • White blood cell (WBC) count greater than 100,000/mm3
Show all 14Show fewer
  • Serum creatinine greater than 2.5 mg/dL
  • Alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN) and/or total bilirubin greater than 3 x ULN
  • Prior chemotherapy (other than hydroxyurea) or radiation therapy for AML
  • Known to be human immunodeficiency virus (HIV) positive
  • 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
  • The Investigator believes the subject to be medically unfit to receive the study drug or unsuitable for any other reason
  • Subject with hypersensitivity to decitabine, daunorubicin, cytarabine, or etoposide
  • Has participated in a drug trial in the last 4 weeks.

Trial locations and contacts

22 sites in 3 countries.

22 sites in 3 countries

United States17 sites

  • Study site

    Atlanta, Georgia

  • Study site

    Aurora, Colorado

  • Study site

    Baltimore, Maryland

  • Study site

    Boston, Massachusetts

  • Study site

    Charlotte, North Carolina

  • Study site

    Columbus, Ohio

  • Study site

    Dallas, Texas

  • Study site

    Madera, California

  • Study site

    Miami, Florida

  • Study site

    New Hyde Park, New York

  • Study site

    New York, New York

  • Study site

    Phoenix, Arizona

  • Study site

    Portland, Oregon

  • Study site

    Rochester, Minnesota

  • Study site

    Salt Lake City, Utah

  • Study site

    Seattle, Washington

  • Study site

    Worcester, Massachusetts

Other trials in United States

Australia4 sites

  • Study site

    New Lambton Heights, New South Wales

  • Study site

    Parkville, Victoria

  • Study site

    Subiaco, Western Australia

  • Study site

    Westmead, New South Wales

Other trials in Australia

Canada1 site

  • Study site

    Calgary, Alberta

Other trials in Canada

About this study

Official title: 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.

Being tested
Decitabine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

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

  • DecitabineDrug

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

Study groups in NCT01177540
Study groupRoleWhat they receive
Arm AExperimentalNot described
Receives: Drug: Decitabine
Arm BExperimentalNot described
Receives: Drug: Decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Morphologic Complete Remission (CR)

    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.

    Measured: Day 50

Secondary outcomes (7)

  1. DNA Methylation

    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).

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

  2. Leukemia-free Survival (LFS)

    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.

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

  3. Overall Survival (OS)

    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.

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

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

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

    Measured: Baseline and Day 50

  5. Time to CR

    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.

    Measured: Randomization to Day 50

  6. Time to Neutrophil Recovery

    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.

    Measured: Baseline up to Day 50

  7. Time to Platelet Recovery

    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.

    Measured: Baseline up to Day 38

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2010 (estimated)
  2. Study start3 Mar 2011
  3. Primary completion19 Jul 2013
  4. Study completion19 Jul 2013

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

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01177540
Sponsor's protocol ID
E7373-G000-202
Status last verified
Oct 2013
First submitted
5 Aug 2010
Last updated
28 Jun 2022
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gore L, Triche TJ Jr, Farrar JE, Wai D, Legendre C, Gooden GC, Liang WS, Carpten J, Lee D, Alvaro F, Macy ME, Arndt C, Barnette P, Cooper T, Martin L, Narendran A, Pollard J, Meshinchi S, Boklan J, Arceci RJ, Salhia B. A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML. Clin Epigenetics. 2017 Oct 5;9:108. doi: 10.1186/s13148-017-0411-x. eCollection 2017.

    PubMed 29034009

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Decitabine in people with Pediatric Acute Myelogenous Leukemia (AML), run by Eisai Inc. at 22 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Morphologic Complete Remission (CR) (time frame: Day 50). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01177540, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.

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