A Study of Decitabine (DACOGEN) in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia

Phase 1-2 Safety and Efficacy Study of DACOGEN in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia

The purpose of this study is to examine the safety and efficacy of decitabine in sequential administration with cytarabine in children with relapsed or refractory acute myeloid leukemia (AML).

This is an open-label (identity of assigned study drug will be known) study to evaluate safety, efficacy, and pharmacokinetics (study of what the body does to a drug) of decitabine in sequential administration with cytarabine in children with relapsed or refractory AML. The study will determine the maximum tolerated dose of cytarabine that can be given following decitabine (Phase 1) and the response rate to this combination (Phase 2). Participants may enter a continuation phase of single agent-decitabine infusions for as long as such treatment would be considered beneficial. Serial pharmacokinetic samples will be collected and safety and efficacy will be monitored throughout the study.

Inclusion Criteria:

• Histological diagnosis of acute myeloid leukemia (AML) according to the World Health Organization (WHO) classification
• Diagnosis of AML which has relapsed or is refractory to standard of care and no curative therapy exists
• Karnofsky or Lansky score of at least 50
• Must be recovered from acute toxicity of any prior treatment
• Must have adequate organ function according to protocol-defined criteria
• Agrees to protocol-defined use of effective contraception
• Female participants of childbearing potential must have a negative serum or urine pregnancy test at Day 1 of Cycle 1

Exclusion Criteria:

• Prior treatment with decitabine or azacitidine
• Acute promyelocytic leukemia (M3 subtype in the French-American-British [FAB] classification system)
• CNS3 disease
• acute myeloid leukemia (AML) associated with congenital syndromes such as Down syndrome, Fanconi anemia, Bloom syndrome, Kostmann syndrome or Diamond-Blackfan anemia, or bone marrow failure associated with inherited syndromes
• White blood cell count greater than 40x10^9 cells/liter(L)
• Known allergies, hypersensitivity, or intolerance to decitabine or cytarabine or their excipients
• Contraindications to the use of cytarabine per local prescribing information or prior adverse reactions to cytarabine which would prevent further use
• Currently enrolled in the treatment phase of an interventional investigational study
• Female who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug (however, the period after which it becomes safe to become pregnant after the last dose of treatment is not known)
• Male who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments
• Any social or medical condition that in the investigator's opinion renders the participant unfit for study participation
• History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease
• History of human immunodeficiency virus (HIV) antibody positive