Clinical trial NCT01177540: Efficacy and Safety of Decitabine as Epigenetic Priming With Induction Chemotherapy in Pediatric Acute Myelogenous Leukemia (AML) Subjects
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pediatric Acute Myelogenous Leukemia (AML)
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-08-09
Enrollment: 25
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Morphologic Complete Remission (CR)
timeFrame: Day 50
Secondary outcomes:
measure: DNA Methylation
timeFrame: Baseline up to completion of induction therapy (Day 15)
measure: Leukemia-free Survival (LFS)
timeFrame: Baseline to recurrence of Leukemia or Death (up to 2 years 5 months)
measure: Overall Survival (OS)
timeFrame: Baseline to Date of Death (up to 2 years 5 months)
measure: Percentage of Participants With Minimal Residual Disease (MRD) at Baseline and Day 50
timeFrame: Baseline and Day 50
measure: Time to CR
timeFrame: Randomization to Day 50
measure: Time to Neutrophil Recovery
timeFrame: Baseline up to Day 50
measure: Time to Platelet Recovery
timeFrame: Baseline up to Day 38
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Madera
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Dallas
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: New Lambton Heights
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Parkville
country: Australia
state: Victoria
city: Subiaco
country: Australia
state: Western Australia
city: Calgary
country: Canada
state: Alberta
Study officials:
affiliation: Eisai Inc.
name: Eisai Medical Services
role: STUDY_DIRECTOR
References:
citation: 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.