Efficacy and Safety of Decitabine as Epigenetic Priming With Induction Chemotherapy in Pediatric Acute Myelogenous Leukemia (AML) Subjects
Condition: Pediatric Acute Myelogenous Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Decitabine; Decitabine
Intervention description: 5 day priming with decitabine followed by Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide).; Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide) only
Intervention MeSH terms: Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 1 Year
Maximum age: 16 Years
Healthy volunteers: No

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.