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

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

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).

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: Decitabine (Dacogen)

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Decitabine (Dacogen); Intravenous injection; total dose-per-cycle was 135 mg/m^2 of decitabine.; Other Names: Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Total Body Clearance (Calculated From Rate and Concentration)	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).	Day 1, Day 2, Day 3
Cmax (Maximum Plasma Concentration)	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).	Day 1, Day 2, Day 3
Tmax (Time at Which Cmax First Observed)	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).	Day 1, Day 2, Day 3
AUC (0-∞) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity	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).	Day 1, Day 2, day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: The Most Frequently Reported Adverse Events (Regardless of Causality)	Summary of All Adverse Events (AEs) by Maximum Grade Occurring in >= 10% Patients	6 weeks

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Gerard Kennealey, MD, Eisai Medical Research (formerly MGI Pharma Inc.)

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: September 30, 2008
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (Estimate): June 22, 2011

Study Record Updates

• Last Update Posted (Estimate): July 12, 2011
• Last Update Submitted That Met QC Criteria: July 2, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: cancer; Acute myelogenous leukemia; myelodysplastic Syndrome
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: DACO-018