Escalation Study to Determine Bioavailability of a Single Oral Dose of Decitabine in Patients With Myelodysplastic Syndrome (MDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00941109
Recruitment Status : Completed
First Posted : July 17, 2009
Last Update Posted : May 9, 2016
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The purpose of this study is to determine how the body absorbs decitabine when taken orally in patients with Myelodysplastic Syndrome (MDS). Safety will also be assessed for this oral dose.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Drug: decitabine Phase 1

Detailed Description:
Cohorts are dosed sequentially, and escalation may stop before the 5th cohort is dosed. Each cycle will be approximately 4 weeks in length. Following Cycle 1, patients may receive an additional 4 follow-up cycles of decitabine. Cycles 2-5 will include a 20 mg/m^2 1-hour IV infusion of decitabine on Days 1-5 for all cohorts.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label, Dose Escalation Study to Determine the Absolute Bioavailability of a Single Oral Dose Administration of Decitabine in Patients With Myelodysplastic Syndrome (MDS)
Study Start Date : December 2009
Actual Primary Completion Date : September 2011
Actual Study Completion Date : September 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Decitabine

Arm Intervention/treatment
Experimental: 1 Drug: decitabine
Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Other Name: Dacogen

Experimental: 2 Drug: decitabine
Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Other Name: Dacogen

Experimental: 3 Drug: decitabine
Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Other Name: Dacogen

Experimental: 4 Drug: decitabine
Cohort 4: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Other Name: Dacogen

Primary Outcome Measures :
  1. Pharmacokinetic (PK) endpoints will be decitabine PK parameters: Tmax, Cmax, AUC0-inf, t1/2 and F. [ Time Frame: Cycle 1 on Days 1 and 2 from predose up to 6 hours after administration. ]

Secondary Outcome Measures :
  1. Safety evaluations will include assessments of adverse events (AEs), medical history, physical examinations, vital signs measurements, use of concomitant medications, and laboratory assessments at baseline and throughout the study period. [ Time Frame: Up to 30 days after the last dose of decitabine ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically confirmed de novo or secondary MDS.
  2. Age greater than or equal to 18 years.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  4. Adequate renal and hepatic function (creatinine less than or equal to 2.0 mg/dL, total bilirubin less than 2.0 mg/dL, aspartate aminotransferase [AST] or alanine aminotransferase [ALT] less than 3 times the upper limit of normal).
  5. Life expectancy of at least 6 weeks.
  6. If currently receiving 5 day decitabine regimen, patient must be scheduled to receive one more cycle of 5 day decitabine.
  7. Recovered from all toxic effects of all prior therapy before entry into this study.
  8. Women of childbearing potential and all men must agree to practice a medically approved form of contraception (one of the following must be used: condoms [male or female] with a spermicidal agent, diaphragm or cervical cap with a spermicidal agent, intrauterine device, hormonal contraception, abstinence) during the course of the study and up to 2 months following the last dose of decitabine.

Exclusion Criteria:

  1. Candidates for up front high dose induction chemotherapy. MDS patients who are scheduled to receive decitabine prior to a bone marrow transplant or stem cell transplant are allowed.
  2. History of treatment failure with decitabine.
  3. Received any experimental agent within the preceding 30 days prior to screening.
  4. Uncontrolled cardiac or pulmonary disease.
  5. History of intestinal surgery, pancreatic surgery, or gastric surgery.
  6. Any clinically relevant disease, disorder (including psychiatric disorders), or condition, in the opinion of the Investigator, which may interfere with the objectives of the study, especially with the gastrointestinal (GI) absorption of the study drug, and/or with the safety of the subject in the study.
  7. Current active colitis of any etiology (Clostridium difficile colitis, ulcerative colitis, Crohn's disease, etc.) or a recent (less than 2 weeks) episode of colitis.
  8. Pregnant or lactating. Female patients of childbearing potential must have had a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to dosing.
  9. Known positive serology for human immunodeficiency virus (HIV).
  10. Active viral, fungal, or bacterial infection. No patient may enter the study unless infections have been fully treated.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00941109

United States, Arizona
Scottsdale, Arizona, United States
United States, Colorado
Denver, Colorado, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, New York
Bronx, New York, United States
United States, Texas
Houston, Texas, United States
United States, Washington
Tacoma, Washington, United States
Sponsors and Collaborators
Eisai Inc.
Study Director: Eisai US Medical Services Eisai Inc.

Responsible Party: Eisai Inc. Identifier: NCT00941109     History of Changes
Other Study ID Numbers: E7373-A001-101
First Posted: July 17, 2009    Key Record Dates
Last Update Posted: May 9, 2016
Last Verified: April 2016

Keywords provided by Eisai Inc.:

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors