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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01177540
First received: August 5, 2010
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Pediatric Acute Myelogenous Leukemia (AML)
Drug: Decitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: 4 weeks post induction chemo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Leukemia Free Survival (LFS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Methylation of DNA [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to platelet recovery and neutrophil recovery following induction chemotherapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Minimal residual disease (MRD) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: March 2011
Study Completion Date: July 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A Drug: Decitabine
5 day priming with decitabine followed by Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide).
Experimental: Arm B Drug: Decitabine
Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide) only

  Eligibility

Ages Eligible for Study:   1 Year to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01177540

  Show 22 Study Locations
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Eisai Medical Services Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01177540     History of Changes
Other Study ID Numbers: E7373-G000-202
Study First Received: August 5, 2010
Last Updated: October 21, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014