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

• ClinicalTrials.gov Identifier: NCT01378416
• Recruitment Status: Completed
• First Posted: June 22, 2011
• Results First Posted: June 22, 2011
• Last Update Posted: July 12, 2011
• Sponsor: Eisai Inc.
• Information provided by: Eisai Inc.

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: Decitabine (Dacogen)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: April 2005
• Actual Primary Completion Date: January 2006
• Actual Study Completion Date: June 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Gerard Kennealey, MD, Eisai Medical Research Inc.
• ClinicalTrials.gov Identifier: NCT01378416
• Other Study ID Numbers: DACO-018
• First Posted: June 22, 2011
• Results First Posted: June 22, 2011
• Last Update Posted: July 12, 2011
• Last Verified: July 2011

Keywords provided by Eisai Inc.:

Acute myelogenous leukemia; myelodysplastic Syndrome; cancer

Additional relevant MeSH terms:

Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Decitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors