Pharmacokinetic Trial of Decitabine (Dacogen) Administered as a 3-hour Infusion to Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Information provided by:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01378416
First received: September 30, 2008
Last updated: July 2, 2011
Last verified: July 2011
  Purpose

The purpose of this study is to determine the pharmacokinetics (PK) of decitabine administered to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).


Condition Intervention Phase
Leukemia
Drug: Decitabine (Dacogen)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic Trial of Decitabine (Dacogen) Administered as a 3-hour Infusion to Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Average Total Body Clearance (Calculated From Rate and Concentration) [ Time Frame: Day 1, Day 2, Day 3 ] [ Designated as safety issue: No ]
    3-hour IV infusion, every 8 hours for three consecutive days. Average Total Body Clearance was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).

  • Cmax (Maximum Plasma Concentration) [ Time Frame: Day 1, Day 2, Day 3 ] [ Designated as safety issue: No ]
    3-hour IV infusion, every 8 hours for three consecutive days. Cmax was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).

  • Tmax (Time at Which Cmax First Observed) [ Time Frame: Day 1, Day 2, Day 3 ] [ Designated as safety issue: No ]
    3-hour IV infusion, every 8 hours for three consecutive days. Tmax was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).

  • AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity [ Time Frame: Day 1, Day 2, day 3 ] [ Designated as safety issue: No ]
    3-hour IV infusion, every 8 hours for three consecutive days. AUC (0-∞) was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).


Secondary Outcome Measures:
  • Safety: The Most Frequently Reported Adverse Events (Regardless of Causality) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Summary of All Adverse Events (AEs) by Maximum Grade Occurring in >= 10% Patients


Enrollment: 16
Study Start Date: April 2005
Study Completion Date: June 2007
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Decitabine (Dacogen)
Intravenous injection; total dose-per-cycle was 135 mg/m^2 of decitabine.
Other Name: Dacogen

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each patient had to meet the following criteria to be eligible for the study:

  1. Patients with MDS (de novo or secondary) must have been 60 years or older and have had disease fitting any of the recognized French-American-British classifications OR chronic myelomonocytic leukemia (with white blood cell [WBC] <12,000/μL) AND have had an International Prognostic Scoring System score of ≥1.5 as determined by complete blood count, bone marrow assessment and bone marrow cytogenetics within 30 days of study entry.
  2. Patients with AML (≥30% bone marrow blasts) must have been age 18 years or older and had previously received standard induction chemotherapy and/or had failed approved therapies.
  3. Must have had Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  4. Must have signed an Institutional Review Board (IRB)-approved informed consent form, indicating his/her awareness of the investigational nature of this study and its potential hazards prior to initiation of any study-specific procedures or treatment.
  5. Must have had adequate renal and hepatic function (creatinine ≤2.0 mg/dL, total bilirubin <2.0 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3.0 X institutional upper limit of normal).
  6. Must have had life expectancy of at least 12 weeks.
  7. Must have recovered from all toxic effects of all prior therapy before entry into this study.

Exclusion Criteria:

  1. Patients with MDS must not have been candidates for high-dose chemotherapy, bone marrow or stem cell transplant.
  2. Must not have had acute promyelocytic leukemia (M3 classification).
  3. Must not have received immunosuppressive therapy for 30 days prior to study entry.
  4. Must not have had central nervous system (CNS) leukemia.
  5. Must not have received systemic corticosteroids, interferon, interleukins or other hormonal therapy within 30 days prior to study entry. Use of corticosteroids (topical and inhaled corticosteroids) was permitted and prophylactic steroids may have been used to treat or prevent transfusion reactions.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01378416

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Gerard Kennealey, MD Eisai Medical Research (formerly MGI Pharma Inc.)
  More Information

No publications provided

Responsible Party: Gerard Kennealey, MD, Eisai Medical Research Inc.
ClinicalTrials.gov Identifier: NCT01378416     History of Changes
Other Study ID Numbers: DACO-018
Study First Received: September 30, 2008
Results First Received: September 30, 2008
Last Updated: July 2, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Eisai Inc.:
Acute myelogenous leukemia
myelodysplastic Syndrome
cancer

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014