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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01378416
• Other study ID #: DACO-018
• Status: Completed
• Phase: Phase 1
• First received: September 30, 2008
• Last updated: July 2, 2011
• Start date: April 2005
• Est. completion date: June 2007

Study information

• Verified date: July 2011
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2007
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Decitabine (Dacogen)
Intravenous injection; total dose-per-cycle was 135 mg/m^2 of decitabine.

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	AUC (0-8) - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity	3-hour IV infusion, every 8 hours for three consecutive days. AUC (0-8) was measured post first dose (Day 1), fourth dose (Day 2), and seventh dose (Day 3).	Day 1, Day 2, day 3	No
Secondary	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	Yes