Clinical trial NCT01853228: A Study of Decitabine (DACOGEN) in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia
Official title: Phase 1-2 Safety and Efficacy Study of DACOGEN in Sequential Administration With Cytarabine in Children With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Acute myeloid leukemia
Relapsed or refractory acute myeloid leukemia
Children
Decitabine
DACOGEN
Cytarabine
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-05-14
Enrollment: 17
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Maximum Tolerated Dose (MTD) of Cytarabine
timeFrame: Cycle 1 (42 days)
measure: Phase 1 and 2: Total Clearance of Decitabine
timeFrame: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 minute (min), 0.5 hour, 1 hour, and 2 hour after end of infusion
measure: Phase 1 and 2: Volume of Distribution at Steady-State (Vss) of Decitabine
timeFrame: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion
measure: Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 1 Day 28
timeFrame: Cycle 1 (28 days) Day 28
measure: Phase 2: Percentage of Participants Who Achieved CR or CRi at Cycle 2 Day 28
timeFrame: Cycle 2 (28 days) Day 28
measure: Phase 2: Percentage of Participants Who Achieved CR or CRi at End of Study Treatment
timeFrame: End of study treatment (approximately 3 years)
Secondary outcomes:
measure: Phase 1 and 2: Maximum Plasma Concentration (Cmax) of Decitabine
timeFrame: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion
measure: Phase 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of Decitabine
timeFrame: Cycle 1 (28 days) Day 5: pre-infusion, 0.5 hour during infusion, end of infusion and at 5 min, 0.5 hour, 1 hour, and 2 hour after end of infusion
measure: Phase 2: Duration of Response
timeFrame: From time of response to relapse, study completion/withdrawal, or death, whichever comes first, for up to approximately 3 years 10 months
measure: Phase 2: Overall Response Rate
timeFrame: Up to approximately 3 years 10 months
measure: Phase 1 and 2: Overall Survival (OS)
timeFrame: From enrollment to death or withdrawal, whichever comes first, for up to approximately 3 years 10 months
measure: Phase 1 and 2: Event-Free Survival
timeFrame: From enrollment to progression/relapse, death, or withdrawal, whichever comes first, for up to approximately 3 years 10 months
measure: Phase 1 and 2: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Approximately 3 years 10 months
Other outcomes:
Locations:
city: Gent
country: Belgium
city: Copenhagen Ø
country: Denmark
city: Paris
country: France
city: Toulouse Cedex 9
country: France
city: Vandoeuvre-Lès-Nancy
country: France
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Stuttgart
country: Germany
city: Rotterdam
country: Netherlands
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: