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.
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
- Conditions the study is for
- Pediatric Acute Myelogenous Leukemia (AML)
- 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
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
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- 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
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
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 group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Not described Receives: Drug: Decitabine |
| Arm B | Experimental | Not described Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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)
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)
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)
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
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
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
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.
- First posted9 Aug 2010 (estimated)
- Study start3 Mar 2011
- Primary completion19 Jul 2013
- 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
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pediatric Acute Myelogenous Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eisai Medical Services, Study director, Eisai Inc.
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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