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

NCT01177540 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: E7373-G000-202
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 22

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.

Conditions

Pediatric Acute Myelogenous Leukemia (AML)

Outcome Measures

Primary Outcomes (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.

  Day 50

Secondary Outcomes (7)

• DNA Methylation

  Baseline up to completion of induction therapy (Day 15)

• Leukemia-free Survival (LFS)

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

• Overall Survival (OS)

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

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

  Baseline and Day 50

• Time to CR

  Randomization to Day 50

Study Arms (2)

Arm A

EXPERIMENTAL

Drug: Decitabine

Arm B

EXPERIMENTAL

Drug: Decitabine

Interventions

Decitabine DRUG

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

Arm A

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (22)

Unknown Facility

Phoenix, Arizona, United States

Location

Unknown Facility

Madera, California, United States

Location

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Worcester, Massachusetts, United States

Location

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

New Hyde Park, New York, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Charlotte, North Carolina, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

New Lambton Heights, New South Wales, Australia

Location

Unknown Facility

Westmead, New South Wales, Australia

Location

Unknown Facility

Parkville, Victoria, Australia

Location

Unknown Facility

Subiaco, Western Australia, Australia

Location

Unknown Facility

Calgary, Alberta, Canada

Location

Related Publications (1)

• 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.

  PMID: 29034009 DERIVED

MeSH Terms

Interventions

Decitabine

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

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

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Eisai Medical Services

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2010
• First Posted: August 9, 2010
• Study Start: March 3, 2011
• Primary Completion: July 19, 2013
• Study Completion: July 19, 2013
• Last Updated: June 28, 2022
• Results First Posted: June 28, 2022

Record last verified: 2013-10

Locations

CA (1); AU (4); US (17)